Screening mammography program delay recommended by Manitoba working group: issues for radiology. Assignment: A working group, appointed by government, examined the advisability of implementing a mammography screening program and prepared a cost analysis. Present Manitoba activity (45,695) is a mixture of clinical mammography (10,000) and unorganized screening, mammographies (35,695) at an annual screening cost of $2.8 million. Canadian policy reports, program descriptions in other countries and critical reviews were analyzed. A steady-state clinical and financial model was constructed. A controlled screening program enrolling 80% of women 50-69 years will cost $2.6 million per year plus $0.65 million new clinical costs limited to 4 years. Recommendations; Six were made: delay implementation awaiting more evidence of benefit, discourage use in asymptomatic women under 50 years, develop information programs for women and health professionals, establish an advisory group and participate in research directed to a eventual decision.


A model for an outpatient imaging center. U.S. federally imposed efforts to regulate joint venturing are a result of certain physician strategies to circumvent anti-kickback statutes by investing in clinics, labs, and facilities for self-referral. This article addresses the ethical debate on physician ownership, MRI as an evolving modality, the 1989 Ethics in Patient Referrals Act and the subsequently released "safe harbors," and finally, describes an existing model for physician/hospital ownership in an outpatient MRI facility.


William Beaumont Hospital Imaging Center design update. The William Beaumont Imaging Center is designed to bridge the gap between conventional and totally digital imaging technology. Reverse capacity and flexibility are designed into the building and it's systems to facilitate the transition at minimal cost and disruption to daily operations.


Radiology department design to accommodate the future introduction of global PACS. In the light of the continuing development of pictorial archiving and communication systems (PACS) and image management and communications (IMAC) systems it is appropriate to consider the provision that should be made in the design of a new or renovated department of radiology to accommodate these new technologies at either an earlier or later date. This paper considers three particular aspects of the influence of PACS on future department design: (1) the requirement for either more or less total department gross square feet, (2) the provision for the specific allocation of spaces at certain locations for PACS equipment and functions, and (3) the provision for dedicated pathways for fiber optic communications among the many locations in the department where PACS components would be located.


Proposed multi-modality network to support image acquisition at remote sites. There is a growing tendency for planners to permit non-radiologists to install isolated radiographic facilities with fluoroscopy in clinical specialty areas. These dedicated facilities are thereby frequently removed from support by radiology. Examples include endoscopy, urology, pulmonology, cardiology, surgery, intensive care, and orthopedics. A multi-modality network tying these remote sites to radiology can restore radiological support. Radiologists can participate in image acquisition procedures even though the procedures are no longer performed in the radiology department. A network also provides the isolated facility with technical support (laser printing, mass storage, etc.) that cannot be economically duplicated for each separate specialty site. A clinical model emphasizing the role of electronic networks in supporting image acquisition (in addition to image display) is undergoing the first phase of implementation at the Veterans Affairs Medical Center (VAMC) in Durham, North Carolina. The planned multi-modality network uses endoscopy as the acquisition model. Both the VAMC network and its extension to the sophisticated endoscopy suite at nearby Duke University Medical Center will be described.


The Vienna SMZO-PACS-project: the totally digital hospital. This paper gives an overview of the SMZO-PACS-Project in the form of a rough specification of the system architecture and the functional parameters related to it. The PACS architecture, determined by the large amount of data volume produced in the SMZO Hospital is outlined. In both radiology and trauma departments high technical requirements concerning data throughout and fault tolerance are demanded. Therefore these PACS modules are designed to minimize the workload of the network so that the performance is not degraded in the case of fault of a single component. A PACS module includes image acquisition devices of a certain modality with related reporting workstations and a distributed electronic archive. The functionality of the modules is described, special interest is posed on the integration of the different information management systems PACS, RIS and HIS, to achieve a complete record of data input and throughput in the hospital.


Integration of radiology and hospital information systems (RIS, HIS) with PACS: requirements of the radiologist. PACS development has now reached a stage where it can clearly be stated that the technology for storage, networking and display in a fully digital environment is available. This is reflected by an already large and rapidly increasing number of PACS installations in USA, Western Europe and Japan. Such installations consist of a great variety of information systems, more or less interconnected, like PACS, HIS, RIS and other departmental systems, differing in both hardware and software. Various data - even if they only concern one person - are stored in different systems distributed in the hospital. The integration of all digital systems into a functional unit is determined by the radiologist's need of quick access to all relevant information regardless where it is stored. The interconnection and functional integration of all digital systems in the hospital determine the clinical benefits of PACS. This paper (1) describes the radiologist's requirements concerning this integration, and (2) presents some realistic solutions such as the Siemens ISI (Information System Interface), and a mobile viewing station for the wards (visitBox).


Sex difference in metabolism of simvastatin by rat hepatic microsomes. Metabolism of simvastatin (SV), a new cholesterol-lowering agent, by hepatic microsomes from male and female rats was investigated. After incubation of [14C]-SV with hepatic microsomes, radioactive metabolites were detected by HPLC. The main metabolite was 3' alpha-hydroxy-SV in male rats and the hydroxy open acid form of SV (SVA) in females. The 3"-hydroxy-SV and 3',3"-dihydroxy-SV which were observed in male rats were hardly detected in females. Specific activity for the metabolism of SV in male rats (3.97 nmol/mg protein/min) was about 9-times higher than that in females. Metabolic activity of hepatic microsomes in male rats was essentially unchanged with increase in age, whereas that in females decreased age-dependently and was very low or negligible after 7 weeks of age. Formation of 3"-hydroxy-SV and 3',3"-dihydroxy-SV in male rats was markedly increased with age, and that in females was negligible at all ages examined.


Pharmacokinetic parameters from data relating to the plasma and biliary excretion kinetics of cefmetazole in rats. The plasma disposition kinetics and the biliary excretion kinetics of cefmetazole after i.v. administration to rats anaesthetized with pentobarbital sodium were studied. Parametric estimation was carried out using non-linear regression methods with uni- and bivariate analyses. On the basis of statistical criteria a two-compartment model was chosen as the most appropriate for fitting the plasma concentration data, establishing a mean half-life value of the slow disposition phase at around 13 min. Analysis of the plasma and biliary data revealed a mean value for the biliary excretion constant of 0.049 l/min and 0.113 l/min for the urinary excretion constant. The cumulative biliary excretion data showed a mean value of 36.25% of the dose administered. The relationship between the biliary excretion rates and plasma concentrations seems to point to a saturable mechanism of excretion.


The in vitro metabolic inversion of R(-) to S(+) indoprofen. The paper reports a study on the metabolic inversion of indoprofen (2-[4-(2-isoindolinyl-1-one)-phenyl]-propionic acid) following incubation of the drug with liver microsomes from non-induced and phenobarbital-induced rats. The enantiomeric composition of the drug was determined after different incubation times of the racemate and the individual isomers. The S(+)/R(-) ratio was evaluated by densitometry following HPTLC separation of the R(+)-1-phenylethylamides. After incubation of the racemate and the individual isomers, no detectable amounts of indoprofen catabolites were extracted from the acidified incubation mixture. An appreciable enrichment in the S(+) enantiomer was observed after incubation of both racemate and R(-)-indoprofen; the S(+)/R(-) ratio reached a maximum after 1 h. Values were higher in the case of induction. After incubation of S(+)-indoprofen, a small but statistically significant decrease of the S(+)/R(-) ratio was observed. The increase of the S(+)-isomer concentration observed following incubation of R(-)-indoprofen can be ascribed to metabolic inversion by phenobarbital-inducible liver enzymes.


Cross-over study of the bioavailability of a new NSAID (droxicam) versus piroxicam in healthy volunteers following single and multiple dose administration. Droxicam is a new anti-inflammatory drug which is a pro-drug of piroxicam and possesses delayed absorption kinetics. In this study, the comparative bioavailability of the two compounds was investigated. The study was performed following a cross-over design with single (20 mg) and multiple (20 mg/day for 30 consecutive days) administration in 25 healthy volunteers. The peak plasma concentrations of piroxicam, obtained following administration of droxicam, were lower than those calculated for administration of piroxicam, and the time taken to reach these peak concentrations was increased by approximately 5-7 h. There was no significant difference in either the elimination kinetics of piroxicam or the AUC values found following administration of the two products. Bioavailability of droxicam is equal to that of piroxicam, with a slower rate of absorption.


Lamotrigine as an add-on drug in the management of Lennox-Gastaut syndrome. We report our experience with lamotrigine add-on therapy in the treatment of 11 patients with Lennox-Gastaut syndrome. Lamotrigine is a novel antiepileptic drug, chemically unrelated to the major anticonvulsants in current use. Ten patients experienced a > 50% reduction in seizure frequency, 1 patient experienced no change in seizure frequency. All patients tolerated lamotrigine satisfactorily and no side-effects were reported.


Asymptomatic homozygous gene carrier in a family with type I familial amyloid polyneuropathy. Type I familial amyloid polyneuropathy (FAP) is a molecular disorder with a mutation of the transthyretin (TTR) gene, and most patients previously examined were reported to be heterozygous for this mutant gene. In the present study a rapid and easy DNA diagnostic method employing the polymerase chain reaction revealed an asymptomatic homozygous TTR gene carrier in a Japanese family with type I FAP. The level of the variant TTR (methionine instead of valine at position 30) in his serum was much higher than that usually found in type I FAP patients. However, the histological findings of the biopsied rectum and abdominal fat tissues failed to demonstrate amyloid deposits, and the autonomic nerves from his rectal mucosa were normally preserved. Moreover, his 72-year-old mother (a TTR gene heterozygote) was supposed to start amyloid deposition in her late sixties. It is suggested that in addition to the mutant TTR gene some other factors control the development of the disease.


Effect of brovincamine on cerebral circulation and metabolism in internal carotid artery occlusion examined by positron emission tomography. We evaluated the effect of brovincamine on the circulatory and metabolic state in the brain ischemia with internal carotid artery occlusion accompanying the 'misery perfusion syndrome'. Cerebral blood flow (CBF), cerebral metabolic rate of oxygen (CMRO2) and oxygen extraction fraction (OEF) were measured by PET before and after intravenous loading of brovincamine. Brovincamine increased CBF and decreased OEF significantly on the occluded side of the hemisphere. CMRO2 did not show any remarkable changes upon brovincamine administration. It was concluded that brovincamine might be useful for increasing the hemodynamic reserve, but did not affect the metabolic state immediately after its administration.


Absorption of intra-bronchial diprophylline-methodology and preliminary results. With the objective of measuring alveolo-capillary permeability, a diprophylline solution (molecular weight 254 D) was instilled as a bolus. Instillation was performed through distallized impacted fiber bronchoscope and 3 normal volunteers and 3 patients with pulmonary fibrosis were evaluated. Blood samples were collected at regular intervals with subsequent pharmacokinetic study, mainly aimed at determining absorption kinetics. This technique enabled us to distinguish the two groups of individuals which had different absorption rates. In controls, kinetics apparently followed a simple, one compartment model for absorption, which was slower and occurred to a lesser extent. Patients with a pulmonary fibrosis had a faster and higher degree of absorption, with a larger plasma Cmax. In the latter group two-compartment kinetics for absorption was found. We conclude that absorption kinetic parameters can disclose data on structural integrity of epithelia and possible lesions of the lung interstitium.


Parlodel SRO in Parkinson's disease: a double-blind randomized comparison of Parlodel standard and Parlodel SRO. In this study, we compared in an intent-to-treat analysis the tolerance and efficacy of Parlodel SRO with its standard galenic formulation in 34 patients with Parkinson's disease who received optimal levodopa therapy. The results suggest that Parlodel SRO was equally efficacious as Parlodel standard, but Parlodel SRO is better tolerated.


Solid-phase extraction of piribedil and its metabolites from plasma and urine without and after deconjugation, by high performance liquid chromatography. A new high performance liquid chromatographic procedure has been developed for the simultaneous quantification of piribedil (PD) and its three main basic metabolites in rat plasma and urine, without and after hydrolysis. The procedure relies on isolation of the compounds from plasma and urine constituents using the Sep-Pak C18 cartridge, with satisfactory recovery and specificity, and resolution by acetonitrile gradient elution on a C18 reversed phase column coupled to a UV detector monitored at 240 nm. The assay was linear over a wide range of concentrations for all compounds in both body fluids with mean within-day and day-to-day coefficient of variation (CV) and relative error (RE) generally below 10%. Plasma concentrations of PD and its metabolites at selected intervals and urinary recoveries of all compounds before and after enzymatic hydrolysis are presented.


Pharmacokinetics of loracarbef in pediatric patients. Loracarbef is an investigational oral antibiotic but its pharmacokinetics have not been studied after multiple oral doses in pediatric patients. The pharmacokinetics of loracarbef were determined in 18 pediatric patients after multiple oral doses. 8 patients with streptococcal pharyngitis received 7.5 mg/kg every 12 h, and 10 patients with otitis media were given 15 mg per kg every 12h. Multiple blood and urine samples were collected to measure loracarbef concentrations. In patients with streptococcal pharyngitis, the mean maximum serum concentration (Cmax), the time to achieve maximum concentration (Tmax), area under the serum concentration-time curve (AUC) and elimination half-life (t1/2) were 10.6 +/- 3.6 mcg/ml, 0.78 +/- 0.21 h, 21.4 +/- 7.2 mcg.h/ml, and 1.2 + 0.4 h, respectively. The mean Cmax, Tmax, AUC and t1/2 were 18.0 +/- 5.4 mcg/ml, 0.83 +/- 0.44 h, 35.6 +/- 9.4 mcg.h/ml, and 1.1 +/- 0.5 h, respectively, in patients with otitis media. The Cmax exceeded the minimum inhibitory concentration of common susceptible pathogens causing pharyngitis and otitis media by severalfold. Nearly 60% of the dose was excreted unchanged in the urine during the dosage interval. The pharmacokinetics were independent of dose. Loracarbef was well tolerated in all patients. These data suggest that loracarbef may be used safely at doses of 7.5 mg/kg every 12 h in pediatric patients with streptococcal pharyngitis and 15 mg/kg every 12 h in those with otitis media.


Myalgia as the major symptom in systemic panniculitis (Weber-Christian disease). A case of systemic panniculitis (Weber-Christian disease) presenting with myalgia as the main clinical symptom is reported. There was no laboratory or electromyographic evidence of myogenic disturbance. Biopsy of the painful muscle revealed nonspecific mononuclear cell infiltration in the epimysial fatty tissue, while the muscle fibers remained intact. Prednisolone was dramatically effective in alleviating the myalgia as well as the other signs of panniculitis. The present case may indicate that myalgia in systemic panniculitis is one manifestation of its systemic connective tissue involvement.


Long-term influence of anticonvulsant agents on calcitonin, parathyroid hormone and osteocalcin. It has been reported that anticonvulsant drugs decrease serum calcitonin; this effect may be dose dependent and/or hypocalcemia dependent. The objective of the present study is to assess such a dependence and to evaluate other parameters in relation to calcitonin. Serum calcitonin, parathyroid hormone and osteocalcin were determined through RIA, and serum calcium, total protein and alkaline phosphatase through an autoanalyzer in 17 patients undergoing long-term treatment with phenytoin and phenobarbital. At the same time, 20 normal subjects were studied and served as controls. In the patients, no changes were observed in calcitonin, parathormone, osteocalcin and calcemia corrected for protein, and there was a statistically significant increase in alkaline phosphatase values (p < 0.001). Calcemia correlated positively with calcitonin (p < 0.01) and negatively with parathormone (p < 0.05). There was no calcitonin correlation with the anticonvulsant dosage or with the total doses ingested. Increased alkaline phosphatase levels in the presence of normal osteocalcin figures suggest a hepatic origin of the former. The fact that there were no calcitonin level changes but a correlation did exist between calcitonin and calcemia leads us to think that any hormonal changes induced by anticonvulsant agents may act indirectly through changes induced in serum calcium.


Acute spinal epidural abscess and spinal leptomeningitis: report of 2 cases with comparative neuroradiological and autopsy study. A 21-year-old male developed back pain, fever, and rapidly progressive quadriparesis. Lumbar tap yielded frank pus which was confirmed on magnetic resonance imaging (MRI) to be located mainly in the cervical epidural space. Conservative antibiotic remedy was partially effective for restoration of the neurological deficits. A 82-year-old female noticed low-back pain which was rapidly accompanied with clouding of consciousness, paraplegia, and sphincter disturbances. Lumbar puncture revealed thick pus which was best depicted on MRI in the thoracolumbar subarachnoid space. At autopsy, spinal subarachnoid abscess or leptomeningitis was confirmed, and a spinal infarction previously unrecognized on MRI was found. Usefulness and shortcomings of MRI in the diagnosis of paraspinal infections are discussed.


Pharmacokinetics of cadralazine and its hydrazino-metabolite in patients with renal impairment after repeated administration of 5 mg once daily. Since the hydrazino-pyridazine metabolite of cadralazine, CGP 22 639 is believed to contribute to the activity of the drug, its pharmacokinetics and that of cadralazine were investigated in 8 hypertensive patients with renal impairment. The creatinine clearance (CLcr) of patients ranged from 10 to 60 ml/min. The concentrations of cadralazine in plasma and urine, and of CGP 22 639 (plus its possible hydrazones) in plasma were measured after single and repeated administration of 5 mg of cadralazine once daily. A hypotension possibly linked to cadralazine treatment was recorded on day 3 for the patient with CLcr = 10 ml/min. Metabolite concentrations were found to be at least twice as high as in other patients indicating that in this patient, the daily dose of 5 mg was probably too high. The pharmacokinetics of cadralazine were not modified by repeated administration. The drug and its metabolite were eliminated more slowly in patients with low creatinine clearance. The t1/2 of CGP 22 639 was about twice the t1/2 of the unchanged drug. In patients whose CLcr ranged from 19-37 ml/min the mean accumulation factor of apparent CGP 22 639 was 1.7 times that of the unchanged drug. It shows that the apparent CGP 22 639 accumulated more than the unchanged drug. A starting daily dose of 2.5 mg of cadralazine in patients with CLcr < 40 ml/min appears to be suited to take into account the pharmacokinetics of CGP 22 639. This dose can be increased by 2.5 mg steps if the antihypertensive effect is not sufficient (maximum dose with CLcr < 40 ml/min: 10 mg).(ABSTRACT TRUNCATED AT 250 WORDS)


The effects of long-term occupational exposure to carbon disulphide on serum lipids. No definite conclusion can be made from many epidemiological and clinical studies of lipid metabolism in workers exposed to carbon disulphide (CS2). The aim of our investigation was to study the serum lipid levels in workers exposed to different CS2 levels to establish possible exposure-response relationships. The first group, spinners, were exposed to high CS2 levels; the second group, workers in viscose production, to low CS2 levels; and the third group included non-exposed workers. As a part of a large examination, total and free serum cholesterol, total lipid and triglyceride levels were determined. Mean total lipid levels were similar in high and low CS2 exposed workers, but significantly lower in non-exposed workers. The total serum cholesterol mean levels were also similar in both groups, but significantly higher in the non-exposed group. Only serum triglyceride values were related to the CS2 levels: the most elevated were in the high exposed workers, somewhat lower in the low exposed, and the lowest in the non-exposed group. The finding is especially important as triglycerides are the most specific for developing atherosclerosis, which is often reported in workers with long-term exposure to carbon disulphide.


Pharmacokinetics of heptacaine, a novel potent local anaesthetic agent, after rectal administration to rats. The pharmacokinetics of heptacaine, N-(2-(2-heptyloxyphenylcarbamoyloxy)ethyl)-piperidinium chloride, a new long-acting potent carbanilate type local anaesthetic, proposed for local anaesthesia in complex treatment of hemorrhoids, was studied following its rectal administration to rats in the form of cocoa butter suppositories. The heptacaine plasma concentration, 0.0083% of dose/ml, peaked at 90 min post administration and the maximum rate of its bioavailability, 0.19% of dose/min, assessed by deconvolution, occurred 38 min post administration. The plasma elimination half-life of heptacaine was 133 min and its biological availability of 52% was comparable to other agents of the class.


Significance of white matter lucencies in posthypoxic-ischemic encephalopathy: comparison of clinical status and of computed and positron emission tomographic findings. The clinical status and the computed and positron tomographic findings were compared in 10 patients with sequelae of hypoxic-ischemic encephalopathy after cardiopulmonary arrest and successful resuscitation. Conscious patients with moderate neuropsychiatric deficits had no significant computed tomography (CT) scan changes and normal values of regional cerebral blood flow and oxygen consumption, while patients in vegetative state had definite cerebral atrophy on CT scan and a severe and widespread decrease of regional cerebral blood flow and oxygen consumption. This decrease was even more pronounced in vegetative patients with the worst neurological score and with CT scans demonstrating additional diffuse white matter lucencies and hypodensities in the basal ganglia. In this group of patients increased regional oxygen extraction rates mainly in the white matter indicated the occurrence of delayed ischemic changes. The positron emission tomography and CT findings correlated well with the degree of posthypoxic-ischemic damage and the clinical status of the studied subjects.


Isolated prolonged retrograde amnesia.

Isolated prolonged retrograde amnesia. We describe a patient who had isolated retrograde amnesia of 1-year duration without anterograde amnesia after recovery from encephalitis. Single photon emission computed tomography using 123I-IMP revealed that left temporal lobe abnormality. We postulate that the learning ability for new information and recalling ability for old information involve different neural structures, and there is a possible relationship between isolated retrograde amnesia and left temporal dysfunction.


Comparative multiple-dose pharmacokinetics of controlled-release levodopa products. The multiple-dose (200 mg levodopa t.i.d.) pharmacokinetic profile of two controlled-release products of levodopa (Madopar HBS and Sinemet CR) was compared to conventional Madopar capsules in 18 healthy volunteers in a cross-over, randomized design. A pronounced controlled-release profile of the Madopar HBS and Sinemet CR product was demonstrated compared to conventional Madopar capsules with a significant (p < 0.001) decrease (-40 and -55%) in Cmax and a significant (p < 0.001) increase (+237 and +256%) in morning Cmin for the 200 mg t.i.d. dosage schedule. Almost equivalent bioavailability (85-90%) of levodopa was demonstrated for the controlled-release formulations relative to that of conventional Madopar capsules. The Madopar HBS formulation was bioequivalent with Sinemet CR with respect to levodopa, but it exhibited a moderately higher fluctuation index compared to Sinemet CR as a result of somewhat higher Cmax and lower Cmin values for the Madopar HBS formulation. 3-OMD (a metabolite of levodopa) levels were significantly (p < 0.05) higher for Madopar HBS and Madopar compared to Sinemet CR. The higher 3-OMD levels for the levodopa/benserazide combinations are consistent with a more potent decarboxylase inhibitory activity of benserazide as compared to carbidopa. The number of adverse events was highest for conventional Madopar (n = 18) compared to the controlled-release formulations (n = 12 for Sinemet CR and only 2 for Madopar HBS). A more efficient inhibition of dopamine formation from levodopa (resulting in higher 3-OMD levels) by Madopar HBS was consistent with the superior tolerability (especially for initial nausea) observed for the Madopar HBS formulation as compared to Sinemet CR.


Orthostatic tremor associated with voice tremor. We report a 67-year-old female with orthostatic and voice tremor. Her orthostatic tremor mainly affected her lower extremities, alternating between antagonist muscle groups at a frequency of 4.4-4.8 Hz. The voice tremor ranged between 4.8 and 8.8 Hz. In this case, the frequency of voice tremor was same as that of orthostatic tremor, suggesting a common origin from a tremor-generating mechanism. These tremors were diagnosed as 'forme fruste' of the essential tremor, not the incipient stage of Parkinson's disease. Medications including clonazepam, perphenazine, Dopa and trihexyphenidyl hydrochloride had no effect on both the orthostatic and voice tremors, but propranolol was somewhat beneficial on voice tremor.


Value of random mucosal biopsies in the management of superficial bladder cancer. 115 newly diagnosed patients with Ta-T1, G1-G2 superficial transitional cell carcinoma of the bladder underwent four quadrant biopsies of normal-looking bladder mucosa, in addition to the endoscopic treatment of the primary tumour or tumours. In 88 (77%) patients all the biopsies were normal; in the other 27 (23%) at least one biopsy revealed dysplasia or carcinoma in situ or G1-G2 carcinoma. 88 patients presented with a single tumour, of which 14 (16%) had abnormal biopsies compared to 13 (48%) of the 27 presenting with multiple tumours. The difference between the 2 groups was statistically significant (p < 0.01). The incidence of freedom from new tumours at 5 years was 68% in patients with normal biopsies compared to 33% in patients with abnormal biopsies (p = 0.002). In patients presenting with multiple tumours and in those with single tumours and abnormal biopsies, the incidence of freedom from new tumours was significantly lower than in those presenting with single tumours and normal mucosal biopsies (p = 0.002). The study shows that the exercise of performing random mucosal biopsies is particularly useful in patients presenting with single tumours, in order to identify those who are more likely to develop new tumours over the longer term. Such patients could be offered early prophylactic intravesical chemotherapy. The study did not substantiate tumour implantation as a factor for new tumour development in superficial bladder cancer.


Successful hyperbaric oxygenation for radiation cystitis due to excessive irradiation to uterus cancer. Six female patients with radiation cystitis, induced by previous pelvic radiation to uterus cancer, were treated with hyperbaric oxygenation (30-35% of oxygen concentration at 2 atmospheric absolute pressures for 90-120 min daily from 20 to 61 days with the average of 45 +/- 7 days, mean +/- standard error). Except in 1 patient symptoms and cystoscopic findings were improved. No side effects were found. Recurrence of radiation cystitis never occurred during the follow-up period (1.0 +/- 0.1 years). Hyperbaric oxygenation treatment in this pressure environment appears to have a beneficial effect of this disorder.


Three-dimensional computed tomographic imaging of the pelvicaliceal system: analysis of factors influencing image quality. We analyzed 3-dimensional (3D) computed tomographic images of the pelvicaliceal system obtained in 25 patients after opacification of the collecting system by retrograde ureteric or intravenous (IV) infusion of sodium iothalamate. 3D images were reconstructed using the data from nonoverlapping 5-mm sections taken on an Elscint 2400 scanner. Factors contributing to poor image quality were: artifacts caused by contrast in the collecting tubules, underfilling or overdistension of the pelvicaliceal system with contrast, movement of the patient and severe hydronephrosis. Satisfactory 3D images of the pelvicaliceal system can be obtained by retrograde ureteric infusion of 5% w/v sodium iothalamate at 20 cm H2O, or by IV injection of 50 ml of 70% w/v sodium iothalamate. Abdominal compression should be applied 10-15 min after the IV injection of contrast, and the computed tomographic examination should commence 20-30 min after the injection. It is imperative that the patient lie completely still and breathe normally to avoid movement of the kidneys. 3D computed tomographic imaging of the pelvicaliceal system may become a valuable adjunct to the preoperative planning and performance of percutaneous nephrolithotomy.


Nuclear DNA analysis: DNA heterogeneity in the monitoring of patients with locally advanced prostatic carcinoma. Single-cell DNA cytophotometry was employed to analyze the tumors of 271 patients with locally advanced prostatic carcinoma as to DNA ploidy and heterogeneity and the distribution of the phases of the cell cycle before and during therapy, with the intention of establishing prognostic factors apart from those already known (stage, grade). Follow-up periods ranged from 1 to 9 years. 198 (73%) of the 271 patients had carcinoma stage T3 N0 M0, and 73 (27%) of them had carcinoma stage T3/T4 N+M1. The tumors were evaluated cytologically to establish the grades of malignancy. 11.8% were grade I carcinoma, 64.3% were grade II and 23.9% were grade III carcinoma. Single-cell DNA cytophotometry demonstrated aneuploidy rates of up to 73% and diploidy rates of up to 23.8% for the higher grades of malignancy, whereas the diploidy rate established for grade I carcinoma was 71% and the respective aneuploidy rate was 15.2%. These differences are significant (p < 0.001). There was a significant correlation between the results of DNA cytophotometry and the clinical course of the disease. Patients with diploid tumor cell nuclei developed no metastases and no local tumor progression during the follow-up period of 9 years, whereas patients with aneuploid tumor cell nuclei showed metastases and local tumor progression within 8-22 months, despite changes in therapy. These patients died of carcinoma after an average 18 months following primary diagnosis.


DNA content, nuclear grading and early tumor progression in renal cell cancer: a prospective study on frozen specimens. Renal cell carcinoma is a neoplasia with an unpredictable behavior. Nuclear grade and pathologic stage are widely accepted as valuable prognostic factors. More recently DNA content has been proposed as an adjunctive parameter of the clinical course of the disease. In order to substantiate these findings we prospectively analyzed 36 frozen specimens from patients submitted to radical nephrectomy for renal cell carcinoma. The study population had a 2:1 male/female ratio with a median age of 57 years. Six of 33 patients died of tumor progression with a median survival time of 11 months. The tumor DNA index (DI) ranged from 0.86 to 2.06 with a mean coefficient of variation of 4.59. Ten cases (27.8%) had a diploid DNA content, whereas 26 (72.2%) showed a distinct aneuploid population. In 10 cases different DI values were observed in different samples from the same tumor. Aneuploidy was significantly associated with advanced pathologic stages, high nuclear grade, and tumor progression.


DNA flow cytometry and neo-adjuvant chemotherapy/radiotherapy in operable muscle-invasive bladder carcinoma. A preliminary report. Fifty-five patients with muscle-invasive transitional cell carcinoma of the bladder were treated with preoperative cisplatin-based chemotherapy followed by radiotherapy (20 Gy within 1 week) and cystectomy. DNA flow cytometry (FCM) was performed in paraffin-embedded tissue obtained by transurethral resection immediately before therapy. Together with the T-category and histological grade, DNA ploidy and S-phase fraction (SPF) were evaluated for the ability to predict the response to chemotherapy/radiotherapy and survival: a low T-category, but neither DNA ploidy nor SPF, was predictive for the response to neo-adjuvant treatment. The T-category was not related to the patients' survival. In the Cox regression analysis, SPF was an independent prognostic parameter together with response to the precystectomy therapy. We concluded that, in spite of remaining technical problems, paraffin-embedded tissue from bladder carcinoma is suitable for DNA FCM. Contrary to the situation in superficial bladder cancer, DNA ploidy is not related to the clinical outcome in muscle-invasive bladder carcinoma treated by neo-adjuvant chemo-/radiotherapy and cystectomy. SPF seems to be a clinically worthwhile parameter with significance that has to be further studied in larger series.


Ectopia of the vas deferens into the ureter. Case report and review of the literature. Ectopia of the vas deferens into the ureter is a rare occurrence, frequently associated with anorectal anomalies. To date, 20 cases have been reported, accounting for a total of 26 vasoureteral communications, 6 of which are bilateral. Embryologically, ureteral ectopia of the vas deferens may be explained by an underlying defect in the proximal mesonephric duct or an abnormally cranial origin of the ureteric bud. We add the case of a newborn with an ectopic vas terminating into the ureter of a multicystic kidney.


Simultaneous bilateral adrenal metastases from renal cell carcinoma. Surgical implications and review of the literature. We report a case of left-side renal cell carcinoma with contemporary bilateral adrenal involvement discovered preoperatively with computerized tomography and other imaging techniques. Surgical treatment consisted of radical nephrectomy with a nearly total contralateral adrenalectomy and the unroofing of a lower pole renal cyst. Postoperative cortisone acetate replacement was instituted. The surgical implications of renal cell carcinoma with metastasis are also discussed.


Blue nevus of the prostate: report of two new cases with immunohistochemical and electron-microscopic studies. Two new cases of prostatic blue nevus are studied with routine histological, immunohistochemical and ultrastructural methods. Both cases showed a chronic lower urinary tract obstruction due to a benign prostatic hyperplasia with spindle-shaped stromal cells loaded with melanin pigment. These cells were positive for S-100 and negative for HMB-45 antibodies, being, to the best of our knowledge, the first time that this antibody has been tested in prostatic pigmented lesions. The electron-microscopy study was performed in the first case, confirming the nature of these pigmented cells as melanocytes derived from the neural crest showing melanosomes in all the stages of differentiation and without complete basal cell membrane. The histogenesis of pigmented lesions of the prostate and the differences between blue nevus and melanosis are discussed, and the literature is reviewed.


Serotonin-induced dilation of small arterioles is not mediated via endothelium-derived relaxing factor in skeletal muscle. Serotonin (5-HT) dilates precapillary arterioles in skeletal muscle. The purpose of this study was to determine if 5-HT releases endothelium-derived relaxing factor (EDRF) in this tissue. Diameters of third-order arterioles (A3) in the cremaster muscle of pentobarbital-anesthetized rats were measured via videomicroscopy. Concentration-response curves for acetylcholine, nitroprusside and 5-HT were obtained before and after the application of either hydroquinone (5 x 10(-4) M) or NG-nitro-L-arginine (10(-4) M). The involvement of prostaglandins was eliminated by ibuprofen (10(-4) M). In one group, 5-HT (20 micrograms/kg) and NG-nitro-L-arginine were given i.v. (30 mg/kg). The non-EDRF-dependent vasodilator papaverine (10(-5) M) was applied at the end of the protocol to determine the maximal resting diameter. When applied topically, both hydroquinone and NG-nitro-L-arginine significantly inhibited the dilation induced by acetylcholine, but neither agent affected the dilation to nitroprusside or 5-HT. NG-Nitro-L-arginine (i.v.) attenuated acetylcholine-induced dilation but not the dilation to intravenous 5-HT. These data suggest that 5-HT-induced dilation of small arterioles in skeletal muscle is EDRF-independent.


Subclasses of purinoceptors in feline bladder. Purines have been shown to inhibit and excite feline detrusor smooth muscle through P1 and P2 receptor activation. Several recent studies have demonstrated differences in agonist potency orders for subclasses of purinoceptors, including P2Y and nucleotide, or P2U receptors. The current studies were performed to determine the presence of such receptor subtypes in feline detrusor smooth muscle. Cats were surgically prepared for monitoring detrusor smooth muscle contractions as increases in intravesical pressure. Contractions were induced by pelvic nerves stimulation (PNS), ATP, and ATP analogs, such as beta, gamma-methylene ATP (APPCP), 5' adenylimido diphosphate (AMP-PNP) and 2-methylthio ATP (2-MeSATP), ATP gamma S, UTP, CTP and GTP. These agents all produced contractions and had an agonist potency order of AMP-PNP = APPCP > ATP gamma S = 2-MeSATP >> ATP > UTP = CTP = GTP. The agonist potency order for inhibition of PNS nerve-evoked bladder contractions was APPCP = AMP-PNP = ATP gamma S > 2-MeSATP = ATP > UTP = CTP = GTP. Reactive Blue 2 and Coomassie's Brilliant Blue G, two putative P2Y receptor antagonists, antagonized purine-induced actions. This antagonism and the agonist potency orders suggest the possible presence of novel receptors in detrusor smooth muscle and/or the presence of multiple receptors in detrusor smooth muscle.


Bradykinin-induced airway responses in guinea pig: effects of inhibition of cyclooxygenase and thromboxane synthetase. We studied the effects of indomethacin (10 mg/kg i.v.), a cyclooxygenase inhibitor, and OKY-046 (1, 10 and 30 mg/kg i.v.), a selective thromboxane synthetase inhibitor, on airflow obstruction and airway plasma exudation induced by bradykinin (150 nmol) instilled by the airway route to anesthetized guinea pigs. To do this, we studied changes in lung resistance (RL) and extravasation of Evans Blue dye respectively. Instilled bradykinin produced an immediate and marked increase in RL which peaked at approximately 30 s. We also observed a delayed increase in RL, reaching a second peak at approximately 3 min. Bradykinin produced airway plasma exudation at all airway levels, measured as extravasation of Evans Blue dye. Indomethacin significantly inhibited both the immediate and the delayed increase in RL after bradykinin. OKY-046 had a similar significant and dose-dependent inhibitory effect on these responses. In addition, both drugs inhibited bradykinin-induced Evans blue dye extravasation in intrapulmonary airways. Bradykinin instilled by the airway route significantly decreased systemic blood pressure but this effect was not altered in animals pretreated with either indomethacin or OKY-046. We conclude that the bronchoconstrictor response and airway plasma exudation induced by instilled-bradykinin may be mediated in part via thromboxane A2 generation.


Effect of endothelin-3 on cytosolic calcium level in vascular endothelium and on smooth muscle contraction. In isolated rat aorta, endothelin (ET)-3 increased cytosolic Ca2+ ([Ca2+]i) in the endothelium at a concentration (100 nM) which had little effect on muscle resting tone. In the absence of external Ca2+, ET-3 still transiently increased endothelial [Ca2+]i. Verapamil (10 microM) did not change the effects of ET-3. In aortas stimulated with 100 nM norepinephrine, 100 nM ET-3 relaxed the muscle with an increase in endothelial [Ca2+]i. An inhibitor of nitric oxide synthase, 100 microM NG-monomethyl-L-arginine, inhibited the relaxant effect of ET-3 but not the increase in endothelial [Ca2+]i. In the absence of the endothelium or in the presence of an antagonist of ETB receptors, 3 microM IRL 1038, the ET-3-induced increase in endothelial [Ca2+]i and relaxation of norepinephrine-induced contraction were inhibited. Under these conditions, ET-3 increased smooth muscle [Ca2+]i and induced contraction, both of which were inhibited by an inhibitor of ETA receptors, 3 microM BQ123. These results suggest that ET-3 acts on ETB receptors in the vascular endothelium to increase [Ca2+]i by releasing Ca2+ from storage sites and by opening non-L type Ca2+ channels, activates nitric oxide synthase, releases nitric oxide and relaxes vascular smooth muscle. Although ET-3 also activates ETA receptors in smooth muscle to induce contraction, this effect is overcome by the relaxant effect mediated by ETB receptors.


Alterations in vasoactive intestinal polypeptide-related peptides after pentylenetetrazole-induced seizures in rat brain. The possible involvement of vasoactive intestinal polypeptide-related peptides in pentylenetetrazol (PTZ)-induced seizures in rats was investigated. The chemoconvulsant PTZ was administered (45 mg/kg i.p.) either acutely or chronically for three days. The detailed time course of changes in VIP-(1-28) and VIP-(22-28) was examined in several rat brain areas 5 and 20 min and 24 h after acute treatment and after three days chronic treatment. Ir-VIP levels dramatically decreased in all areas 5 min after PTZ injection, remained low after 20 min and progressively increased back to control values after 24 h and after three days of repeated treatment (except for the cortex). Chromatographic analysis of extracts prepared from PTZ-treated rats revealed a concomitant decrease in VIP-(1-28) and increase in VIP-(22-28). Thus VIP-(22-28) might be a product of the internal cleavage of the precursor VIP-(1-28) after its neuronal release; alternatively, VIP-(22-28) might be generated by post-transcriptional processing of VIP-(1-28), and thus be an 'independent' neuropeptide. The results suggest that VIP-(1-28)/VIP-(22-28)-containing neurons might be involved in PTZ-induced seizures in rat brain, and that VIP-(22-28) might play a role in these experimental seizures.


Nitric oxide in gastroprotection by aluminium-containing antacids. Pretreatment with aluminium-containing antacids at their original pH or after acidification is known to protect the gastric mucosa against the damaging action of strong irritants and this protection is accompanied by an increase in gastric blood flow (GBF) but the mechanisms underlying these effects have not been elucidated. We investigated the role of endogenous nitric oxide (NO) and prostaglandins (PS) in the prevention of ethanol-induced gastric damage and the alteration of GBF by Maalox and its active component Al(OH)3. Maalox and Al(OH)3 at their original and acidic pH induced dose-dependent gastroprotection accompanied by attenuation of the reduction in GBF caused by 100% ethanol; similar protective and hyperemic effects were recorded after treatment with nocloprost, a locally active PGE2 analog, and nitroglycerin, a donor of NO. Pretreatment with indomethacin that suppressed mucosal PGE2 by about 90%, failed to affect the protective influence of Maalox or Al(OH)3 at their original or acidic pH. On the contrary, pretreatment with NG-nitro-L-arginine (L-NNA), a potent selective inhibitor of NO synthase, reversed the gastroprotective and hyperemic effects of Maalox or Al(OH)3 at original and acidic pH and this reversal was significantly antagonized by L-arginine but not D-arginine. The gastroprotective and hyperemic effects of nocloprost were not influenced by the pretreatment with L-NNA. We conclude that aluminium-containing antacids activate the NO system, which may contribute to the gastroprotective activity of these drugs through an increase in mucosal microcirculation.


Caffeine inhibits depolarization-activated outward currents in rat ventricular myocytes. The effects of caffeine (10 mM) on depolarization-activated, calcium-independent outward K+ currents were investigated in isolated rat ventricular myocytes, using whole-cell clamping. The external solution contained CoCl2 2 mM and the internal solution contained ethylene glycol-bis(-aminoethyl ether) N,N,N',N'-tetraacetic acid 10 mM. Caffeine decreased the peak amplitude of the total current and the sustained plateau current. Caffeine did not modify the steady state inactivation curve, which was fitted by two Boltzmann functions. Caffeine blocked the tetraethylammonium-sensitive slowly activating and inactivating outward current by 32% and the 4-aminopyridine-sensitive rapidly activating and inactivating transient outward current by 19%. Caffeine did not modify the inactivation rate or the time course of the recovery from inactivation of the transient current. Ryanodine 10 microM did not modify any of the current components and the effect of caffeine was not modified by ryanodine pretreatment. The phosphodiesterase inhibitor, 3-isobutyl-1-methylxanthine 100 microM, did not modify the depolarization-activated calcium-independent outward currents.


The thromboxane receptors of rat and guinea-pig lung. The thromboxane (TXA2) receptors on rat and guinea-pig lung strips were compared using TXA2 agonists and TXA2 receptor antagonists. On rat lung strip several TXA2 mimetics were full agonists whilst the primary prostanoids lacked agonist activity. On guinea-pig lung strip the same agonists displayed markedly different efficacies. Both preparations contained homogeneous populations of TXA2 receptors as evidenced by BAY u3405 giving comparable pA2 values against four TXA2 mimetics. However, the observed pA2's of nine different TXA2 receptor antagonists, determined against U46619, did not correlate between the two preparations. These results point to the existence of TXA2 receptor subtypes.


Ro 40-5967, a novel calcium channel antagonist, protects against ventricular fibrillation. Ro 40-5967 is a new calcium channel antagonist that binds at the same membrane sites as verapamil, yet has minimal negative inotropic effects. The effects of Ro 40-5967 on the susceptibility to ventricular fibrillation were investigated and compared to diltiazem. Ventricular fibrillation (VF) was induced in 40 mongrel dogs with healed myocardial infarctions by a 2-min coronary occlusion during exercise. Twenty-four animals were found to be susceptible to VF and were given the treatments described below. Pretreatment with Ro 40-5967 (n = 17, 1000 micrograms/kg i.v.) significantly (P < 0.001) reduced the incidence of VF (13 of 17 protected) during the exercise plus ischemia test. Diltiazem (n = 8, 1000 micrograms/kg) completely suppressed VF. Lower doses of diltiazem and Ro 40-5967 did not prevent VF. The hemodynamic effects of Ro 40-5967 were also compared to diltiazem and verapamil. Diltiazem and verapamil, but not Ro 40-5967, increased P-R interval in a dose-dependent manner. Even when reflex tachycardia was controlled by beta-adrenoceptor blockade, Ro 40-5967 still exerted only minimal effects on P-R interval. Verapamil, but neither Ro 40-5967 nor diltiazem, provoked a dose-dependent negative inotropic response. All three drugs elicited large increases in coronary blood flow. These data support the hypothesis that calcium entry may play a critical role in the development of malignant arrhythmias during ischemia. Further, Ro 40-5967 can protect against ventricular fibrillation without significant negative inotropic or dromotropic effects.


Blockade of endothelium-derived relaxing factor synthesis with NG-nitro-L-arginine methyl ester leads to enhanced venous reactivity in vivo. This study was performed to examine whether endothelium-derived relaxing factor (EDRF) influences venous tone and reactivity in vivo. The inferior vena cava and abdominal aorta were studied simultaneously under continuous haemodynamic monitoring in anaesthetised rabbits. In addition, a 20-MHz intravascular ultrasound catheter was placed in the vena cava for on-line two-dimensional imaging of vessel cross-sectional area and calculation of wall stress (T(ension) = P(mean) * r(adius)/2). This approach enabled simultaneous visualisation of both venous (CA(ven)) and aortic (CA(art)) cross-sectional area with continuous recording of vessel dimensions. Measurements were made before and after administration of NG-nitro-l-arginine methyl ester (L-NAME; 10 mg.kg i.v.), a specific inhibitor of EDRF biosynthesis. After L-NAME there was a significant increase in central venous pressure and a decrease in CA(ven). On the arterial side, L-NAME caused a significant increase in mean pressure and CA(art), resulting in a significantly augmented arterial wall stress. The venodilatation elicited by increasing doses of glyceryltrinitrate was markedly enhanced after L-NAME. Norepinephrine caused a parallel shift of the dose-response curve for CA(ven) in the presence of a lower baseline value. These results suggest that EDRF contributes substantially to the control of large capacitance veins in vivo and that L-NAME increases venous reactivity to both norepinephrine and glyceryltrinitrate.


Mechanism of blockade by flunarizine of bovine adrenal catecholamine release. How flunarizine, a class IV Ca2+ antagonist, affects the secretion of catecholamines in response to nicotinic receptor activation (10-s pulses with 100 microM dimethylphenylpiperazinium, DMPP) or direct depolarization of chromaffin cells (10-s pulses with 100 mM K+ and 2.5 mM Ca2+, 100 K+/2.5 Ca2+) was studied in bovine adrenal glands perfused with an oxygenated Krebs-Tris solution at 37 degrees C at a rate of 20 ml/min. Experimental protocols aimed to test voltage and time dependence of the flunarizine blocking effects on secretion are described. The DMPP pulses released an average of 217 micrograms catecholamines and the K+ pulses, an average of 117 micrograms. These responses were blocked by flunarizine concentration dependently; IC50s were 3.7 microM for DMPP and 1.1 microM for K+. Under polarizing conditions (60-s perfusion with a solution containing 5.9 mM K+ and nominally zero Ca2+), a 10-s pulse with 100 K+/2.5 Ca2+ released 117 +/- 26 micrograms of catecholamines (n = 12). Under depolarizing conditions (60-s perfusion with 118 K+/0 Ca2+ prior to the Ca2+ pulse), the pulse with 118 K+/2.5 Ca2+ released 307 +/- 36 micrograms of catecholamines (n = 14). Flunarizine blocked these secretory responses equally and concentration dependently with an IC50 of 3.4 microM under polarizing conditions and of 3.8 microM under depolarizing conditions. Thus, blockade by flunarizine of secretion was apparently not voltage-dependent. The blockade was, however, clearly dependent on the time of exposure of the adrenal medullary tissue to flunarizine.(ABSTRACT TRUNCATED AT 250 WORDS)


Difference in the effects of verapamil on Ca(2+)-activated K+ channels of smooth myocytes of aorta and taenia coli. In freshly dispersed taenia coli myocytes of guinea pig, verapamil decreased the whole-cell outward current during depolarization. In aortic myocytes it has the opposite effect. In cell-attached patches, verapamil increased the frequency of opening of the maxi-K+ channel of both taenia coli and aortic myocytes at the expense of the mean open time. In taenia coli myocytes, the greater frequency did not fully compensate for the reduced open time, and the overall open probability of the channel was reduced. In aortic myocytes, the increase in open frequency overwhelmed the effect of the decrease in mean open time. None of the effects could be reproduced with nifedipine or diltiazem in either cell type.


Acute effects of gamma-vinyl GABA on the GABAergic system in rats as studied by microdialysis. The acute effects of the irreversible gamma-aminobutyric acid (GABA) transaminase inhibitor, gamma-vinyl GABA (Vigabatrin), were studied in the central nervous system of the rat. GABA concentrations were monitored in the hippocampus by implantation of microdialysis probes. Two doses of gamma-vinyl GABA (1.6 and 8.0 mM) were administered via the probes and were found to cause a transient increase in the basal GABA outflow (10-fold) during the period of drug administration. In addition, gamma-vinyl GABA pretreatment (1.6 mM) seemed to decrease K(+)-evoked GABA release (P < 0.05). The immediate increase of GABA outflow after gamma-vinyl GABA administration may be the result of direct blockade of GABA uptake sites, a finding which further indicates that the action of GABA transaminase inhibitors may be mediated partly through GABA uptake inhibition.


Involvement of endogenous nitric oxide in the regulation of rat intestinal motility in vivo. The effect of the nitric oxide (NO) synthase inhibitor, NG-nitro-L-arginine methyl ester (L-NAME) on the motility of the small intestine in an acute model in the anaesthetised rat was determined by changes in jejunal intraluminal pressure. L-NAME (0.5-10 mg kg-1 i.v.) caused a dose-dependent increase in intraluminal pressure and initiated phasic intestinal contractions. These responses were inhibited by concurrent administration of L-arginine (200 mg kg-1 i.v.) but not by D-arginine (200 mg kg-1). The increase in jejunal motility induced by L-NAME was attenuated by atropine (4 mg kg-1), although even high doses of atropine (16 mg kg-1) did not abolish these responses. This indicates that although there are interactions between NO and muscarinic cholinergic mechanisms, other processes are also involved in these contractile events following administration of L-NAME. These observations in the rat suggest that endogenous NO plays a role in the modulation of intestinal motility in vivo.


Does the continuous use of bronchodilators mask the progression of asthma or chronic bronchitis? Recently, we published data of a 2 year randomized controlled study in which the effects of continuous versus symptomatic bronchodilator treatment in patients with moderate asthma or chronic bronchitis were investigated. The results showed that FEV1 decline in the continuously treated group was significantly larger than in the symptomatically treated group (72 versus 20 ml/year, P < 0.05). We reanalysed these data in order to investigate the hypothesis that the continuous use of bronchodilators may mask a rapid decline in lung function. Lung function decline was assessed by regression analysis of seven FEV1 measurements. Respiratory symptoms were assessed by means of the MRC questionnaire every 12 months, and they were also recorded by the patients in a weekly report. Of the participating patients 144 completed the study. Increased lung function decline in the continuously treated group was not reflected in a significant deterioration of the symptoms. Moreover, the decline in FEV1 showed no correlation at all with changes in respiratory symptoms in continuously treated patients (r = -0.03, P = 0.80), whereas in the symptomatically treated group, there was a better relation (r = -0.32, P = 0.003) to changes in respiratory symptoms. These results show that continuous bronchodilation may indeed mask the worsening of the disease. This lack of awareness of deterioration of the disease is probably caused by the continuous symptom relief of bronchodilators. It may be misleading to both patients and physicians.


New insights into irritable bowel syndrome. A literature study. 439 papers on the irritable bowel syndrome (IBS) were listed in the Index Medicus and FAMLI in the period from the beginning of 1985 to the end of 1990. From these 439 papers 58 research reports were selected for a literature study into new insights into the aetiology, diagnostics and therapy of IBS. After these research reports had been evaluated according to eight criteria, the relevance of the research results for general practice was assessed. Many studies had methodological flaws. Often no hypotheses had been formulated. Only one-third of the research reports addressed the question of the validity and reliability of the measuring instruments used. Most of the investigations involved a strongly selected research population. The aetiology of IBS remains obscure. The general practitioner can make the diagnosis of IBS himself using straightforward diagnostic methods. No specific form of therapy is effective in the case of IBS. The policy of physicians concerning patients with IBS will have to be directed towards helping them cope with chronic complaints for which there is no adequate explanation.


The diagnostic value of symptoms for the identification of patients with an increased risk of colorectal disease. A criteria-based analysis. In most textbooks of gastroenterology, diseases with their symptoms are discussed. The exact diagnostic value of these symptoms, however, regarding the differentiation between organic and functional disease, is not mentioned. A criteria-based meta-analysis of the few existing studies in this field was done. From the 14 identified studies, there were two that did not find any significant symptoms. In the other studies the diagnostic value of colonic symptoms showed great variability. Methodological deficiencies in these studies are probably responsible for the latter. The generalization of these results into general practice is not straightforward and needs research in general practice patients.


Testing for cervical Chlamydia trachomatis infection in an inner city practice. The aims of the study were to find the prevalence of cervical Chlamydia trachomatis infection in women attending for a speculum examination, to examine possible risk factors, and to see if we could develop a rational policy for testing for chlamydia in our deprived inner London practice. During 18 months 409 women aged 17-45 (mean 28) who attended for a cervical smear or vaginal examination were tested for chlamydia using the direct immunofluorescent test. They were assessed for possible risk factors: age less than 25, more than one sexual partner in the previous 3 months, sexual contact with men with urethritis, past history of chlamydia infection, purulent vaginal discharge, cervicitis and abnormal cervical cytology. Thirty-six women (8.8%) were chlamydia positive. Chlamydia infection was significantly associated with the presence of purulent vaginal discharge or an inflammatory cervical smear. In view of the prevalence of chlamydial cervicitis, the lack of symptoms and signs, and the potential consequences of untreated infection, ideally all young women in this population should be offered screening when they attend for a speculum examination. If this is not practical, chlamydia testing might be offered to women thought to be in high-risk groups including those with purulent vaginal discharge or an inflammatory cervical smear.


Fever in general practice. II. Reasons for encounter, management and duration of fever conditions. A sample of 80 direct and 36 telephone encounters for fever was established in 1988 as part of a Norwegian study on fever as a clinical problem in general practice. Reasons for encounter (ICPC) and clinical examinations were recorded along with clinical laboratory tests, treatment, management and follow up (IC-Process-PC). The doctors assessed the diagnostic process by means of visual analogue scale. Duration of the fever conditions was estimated through a postal questionnaire. Patients with direct encounters presented a wide range of reasons for the encounters. Fever was the most frequent single presenting complaint (31%). The general practitioners put major emphasis on the clinical examinations. They prescribed drugs in 68% of the direct encounters. Seventy per cent of the prescriptions were general systemic anti-infectives. Penicillin accounted for 58% of antibiotics. Six (8%) patients were hospitalized, and three (4%) were referred to a specialist. The mean time until complete recovery was 15 days for direct and 19 days for telephone encounters. Fever may be a sign even when it is not a presenting complaint. Major emphasis is probably put on the clinical examination of febrile patients because of the complexity of symptoms and the wide range of diagnoses associated with fever.


The family physician's role in caring for the dying patient and family: a comprehensive theoretical model. Care for the dying patient is a difficult task which arouses many emotions in all participants. Many physicians feel inadequately prepared to cope with the many diverse challenges. A three-dimensional model is described which intends to help physicians better define their role in caring for dying patients. The model comprises direct involvement with the dying patients and their families, the physician's own needs and personal development and the co-operation with other care-givers. This model can be implemented at three levels, according to the physician's experience, skills, feelings, and the situation. The model can serve as a basis for extensive research and as a foundation for curricular innovation for students, residents and continuing medical education.


The general practitioner in Lebanon: is he a potential family physician? A cross-sectional exploratory study was conducted on a group of general practitioners in Beirut, Lebanon to assess the level of family medicine practice among them. Data were collected on the age, sex, number of children, marital status, load of patients per day, field of specialization, if any, and place of study of medicine of 43 general practitioners. The level of family medicine practice was assessed through a self-administered questionnaire containing questions related to the various criteria of family medicine practice. Only 2.3% of the general practitioners had an adequate level of family medicine practice, defined as the top 15th percentile of a maximal score. Doctors were most likely to adhere to the 'informality' criterion and less likely to adhere to the 'family approach', 'ensuring maximal compliance' and 'comprehensiveness of care' criteria. They performed poorly on 'the continuity of care' and on 'the art of medical care' criteria. Overall, family medicine was found not to be adequately practised by the general practitioner and is deemed necessary as a specialty in Lebanon. Suggestions and future recommendations are further presented.


General practitioner records on computer--handle with care. This 1 year prospective study involved nine general practitioners in an urban health centre who routinely record all patient contacts on computer. The study determines by comparison with a manual record how accurately doctors record laboratory investigations on computer and compares the effectiveness of three interventions in improving the completeness of computerized recording of presenting symptoms, problems/diagnoses and laboratory investigations. Recording was analysed for 1 month prior to and for two 1 month periods following each intervention. A control group was used. A total of 7983 patient contacts were analysed. Intervention led to an improvement in the recording of presenting symptoms and problems/diagnoses. Recording of investigations on the computer showed no improvement, remaining at one-third of the total in the treatment room book for both study and control doctors. The effectiveness of the different forms of intervention depended on both the aspect of the consultation considered and the familiarity of individual doctors with the method of data collection. Aspects considered less important required greater intervention to bring about a marked improvement, as did doctors relatively new to the practice. It may not be possible to get all aspects of the consultation recorded with the same degree of accuracy. This has implications for the accuracy of retrospective studies dependent on existing computerized data.


Divorce: different experiences of men and women. Demographic variables, the reasons for the divorce, the changes as a consequence of the divorce and the differences between the sexes were studied among 157 Swedish-speaking spouses through interviews and assessments on visual analogue scales. The results showed that various conflicts were the main reason for the divorce in half of the families. Compared to men, women came significantly more often from broken homes, were the initiators of the divorce in most cases, and felt that the marriage had been dissatisfying for a significantly longer time period. Self-employed men were significantly overrepresented. The changes as a consequence of the divorce were significantly different for men and women in several areas, in most cases in favour of the women.


Short-lived effects of a formulary on anti-infective prescribing--the need for continuing peer review? Because of the introduction of indicative drug budgets in the UK and their likely association with prescribing from a drug formulary, we have studied the effect of the introduction without continued reinforcement of a voluntary practice formulary on antimicrobial prescribing in a group practice. Detailed prescribing feedback for two matched periods before and after the launch of the Northern Ireland Faculty of the Royal College of General Practitioners practice formulary was compared. The parameters chosen were adherence to the formulary, generic prescribing and costs. A slight increase in prescriptions dispensed (3.5%) was observed between the two periods but prescribing costs increased by 32%. There was a 5.9% fall in the number of prescriptions for formulary agents following the launch of the formulary and a major increase (60%; P < 0.01) in the use of non-formulary antimicrobials particularly penicillins and tetracyclines. It was concluded that the high level of formulary prescribing prevalent during the production of the formulary was not maintained following its launch probably because of the lack of reinforcement.


Factors linked to the prescribing of benzodiazepines by general practice principals and trainees. Principals and trainees in general practice attending training events were asked to give information about their prescribing of drugs, with a focus on the prescribing of benzodiazepines for psychological problems. High prescribers of benzodiazepines believed that a prescription saved consultation time, tended to be influenced by drug company information and believed that patients expected a prescription. Low prescribers of benzodiazepines did not prescribe for bereavement, wished to have more psychological expertise and offered treatments other than drugs. Doctors classified as empathic from their statements at interview found difficulty in ending consultations and thought that social problems should be part of the general practitioner's work, although there were no differences between empathic and unsympathetic doctors in overall prescribing rates of benzodiazepines. The data suggest that doctors who are emphatic towards their patients would prescribe less if they had training in psychological skills.


Who do people talk to about healthy lifestyles? A South Australian survey. To investigate who people talk to about healthy lifestyle a personal interview of people in a representative sample of South Australians was carried out. The information was collected by interview from all occupants of selected private dwellings who were aged 15 years or older. The interviewer used a prompt card with nine possible responses and the question asked was "which one of these would you be most likely to talk about healthy lifestyle changes?" Forty-four per cent nominated the general practitioner and 22% a family member. People who were either married or in a de facto relationship (30%) significantly chose a general practitioner more than others (14%) (P < 0.05). In the 30-59 age group more men (12%) than women (6%) chose a family member as a healthy lifestyle adviser (P < 0.05). There was no statistically significant difference in interest in healthy lifestyle in people born in Australia and outside Australia, or in the employed or unemployed. It is suggested that further attention needs to be paid to training in preventive medicine at all levels of general practice education and more needs to be known about the role of family members as healthy lifestyle advisers.


The productive use of threat in primary care: behavioural responses to health promotion. The importance of a scientific understanding of the behavioural change processes involved in certain health promotion interventions is stressed. A model for guiding the behavioural dimensions in health promotion in primary care is presented. This distinguishes between information-giving and -providing skills to facilitate behavioural change. The social factors which impinge upon processes of behaviour change are highlighted. It is suggested that health promotion clinics in primary care may produce a situation with which the client has to cope. The manner of their coping will be a critical factor in determining outcome. Some key organizational issues are underlined.


Health checks in general practice: the patient's response. With the advent of the new GP contract, the offering of health checks in general practice is on the increase. This paper assesses the patient's response to this development. Conducted in a single practice and including 872 patients aged between 30 and 41, the study assessed a number of different invitation letters to, and ways of giving feedback to patients at a health check in terms of the uptake of the service, patients' satisfaction ratings, and changes in patients' health beliefs. A number of important findings emerged. First, almost twice as many patients attended a health check when their invitation letter contained an appointment than when it contained an open invitation. Second, patients' satisfaction with their invitation letters and the information received at the health check was high. However, the health check appeared to increase patients' beliefs in the importance of health professionals in maintaining health. Overall though, the results suggested that the patient's response to the health checks was a positive one, and this may be important in promoting future uptake of preventive services and compliance with advice.


Key factors in health counselling in the consultation. To design an effective course in behaviour influence all GPs and general nurses at two health care centres were interviewed concerning procedure and perceived barriers to prevention. The results demonstrated that most doctors and nurses regarded health counselling as important in medical health service. They also maintained that they have time and space for this activity. However, most doctors and nurses were hesitant and/or disappointed concerning their perceived efficacy in affecting people's life habits. The explanation may be that the personnel lack an effective methodology to handle these issues. Few had a more developed educational theory where the starting-point was the patient. Another explanation may be that many doctors and nurses had a non-patient-centred style, which previous studies demonstrate to be less successful in affecting people's behaviour. This was expressed in the notion that the doctor/nurse has to be a model from which the patient can learn the 'right' life habits. It was also expressed in the notion that the reasons why patients do not change behaviour were mostly psychological, but no importance was attached to the role of different values. The results point out the need for education in patient-centred pedagogics.


Smoking habits in early pregnancy and attitudes towards smoking cessation among pregnant women and their partners. One-hundred and eighty-seven general practitioners in western Norway recorded smoking habits among 2379 women, consulting for their first regular medical check-up in pregnancy. Forty-six per cent had been daily smokers the last 3 months before pregnancy. Thirty-nine per cent were still smoking at the time of their first check-up. Sixteen per cent of the daily smokers stopped smoking spontaneously during the first few weeks of pregnancy. Fifty-seven per cent of women younger than 20 and 28% of women 30 years and older, did smoke at the first check-up. Single women smoked more often than women living with a partner (58% versus 38%). Smoking habits were not associated with number of previous pregnancies. At the first check-up, 530 pregnant women, still smoking daily, 18-34 years of age, living with a partner, accepted to participate in a smoking intervention study. They filled in a questionnaire about their smoking habits, the smoking habits of their partners and their attitudes towards smoking cessation. Sixty-five per cent reported a reduction in their use of cigarettes after becoming pregnant. The mean reduction in the number of cigarettes smoked daily was 4.0 (31%). Most of the respondents expressed a strong motivation to quit or reduce their smoking habits during their pregnancy. Seventy-two per cent of the partners were daily smokers. Reduction in the consumption of cigarettes, negative attitudes towards smoking and determination to stop smoking was significantly higher among women who were encouraged by their partners to stop smoking and in those who perceived that their partners were willing to reduce their consumption.


The effectiveness of lifestyle-related health screening: a 2 year follow-up study of doctors and teachers. The effects of screening a group of 98 general practitioners and teachers for fitness, body mass index, serum cholesterol and lifestyle measures--smoking, alcohol consumption, diet and exercise habits were assessed 6 and 24 months later by postal questionnaire (response rate 98%). There was no significant difference for any screened measure between zero months and 6 or 24 months except that subjects found to have a raised cholesterol at 0 months were subsequently more likely to reduce the proportion of fat in their diet. There were no significant differences between screened subjects compared with a control group of non-screened doctors and teachers at 24 months. The number of subjects with abnormal measurements found at the screening session who altered to measurements within the normal range was equal to the number of subjects who changed from normal to abnormal measurements over the 2 year period of study.


ROC curves for the initial assessment of new diagnostic tests. New diagnostic tests are mainly evaluated by determining the sensitivity and specificity of the test. These test characteristics were originally meant to be used in making diagnoses. For evaluative purposes their usefulness is weakened by their susceptibility to selection and their dependence on the cut-off points that are used for test positivity. The plotting of a receiver operating characteristic (ROC) curve might be a solution to these problems. Furthermore, the ROC curve yields a measure for the diagnostic power of the test expressed in one number instead of two, namely the area under the curve (AUC). Finally, the ROC curve and its AUC permit easy comparison of different tests and the performance of different interpreters of one test. The construction and use of ROC curves are described and illustrated with data of a case-referent investigation into the relationship between iron status parameters and the presence of acute myocardial infarction. The AUCs of ferritin and serum iron, 0.61 and 0.68 respectively, are too low to suggest meaningful usefulness in clinical practice.


Selections from current literature: inhaled steroid use in asthma management. Though our understanding of asthma has improved, its incidence, prevalence and associated death rate have been increasing in most industrialized countries. Inadequate treatment of airway inflammation may explain some of this trend. Steroids are the most effective anti-inflammatory agents and are effective and safe in inhaled form. Together with sodium cromolyn, they should be used more frequently in the management of all types of asthmatics, especially those who require chronic or acute administration of oral steroids.


[Ultrasound studies in pregnancy: technical principles and clinical safety]. Ultrasound examinations in pregnancy were carried out worldwide for over 30 years with no proof of adverse effects on either, mother or child. However, to evaluate the clinical significance of the numerous studies dealing with questions of safety of obstetrical sonography, a basic knowledge of its physical and technical aspects is needed. The present paper aims to convey these basics and should provide a review of the major publications concerned with the clinical safety of the method. Below clearly defined intensity levels, ultrasound scanning in pregnancy can still be considered unhazardous for both mother and child. However, it must be borne in mind, that the safety margin of Doppler flow measurements is lower for duplex compared with B-mode equipment. Therefore, for the present, duplex sonography should not be routinely applied in the first trimester of pregnancy.


[Detection of fibronectin for confirming the diagnosis of premature rupture of fetal membranes]. Diagnosis of premature rupture of membranes (PROM) usually leads to severe clinical consequences. Diagnostic tests for confirmation of suspected rupture of membranes are either unreliable or can adversely affect the pregnancy. Foetal fibronectin is synthesised by the foetoplacental membranes especially in the anchoring villus. Its concentration in the amniotic fluid is 5-10 times greater, than in the maternal plasma. An immunoassay has recently been developed, which detects fibronectin in vaginal secretions using monoclonal antibodies, thereby establishing the presence of amniotic fluid in the vagina. Vaginal specimens were collected from 133 pregnancies. 34 of 35 patients with clearly visible amniotic fluid in the vagina had a positive test result (97.1%), whereas the majority of the control group without any signs of ruptured membranes had negative test results (96.5%). 39 of 41 women with positive test results delivered within 48 hours (95%). A positive test result thus helps to confirm the diagnosis of PROM especially in equivocal cases or may indicate forthcoming labour.


[Telemetric cardiotocography--clinical value and limits of the method in routine monitoring]. Cardiotocography by external telemetry and maternal ambulation has been compared to the usual recording in recumbent position. The visual interpretation extended to several items, such as technical quality, CTG scoring, contractions and foetal activity, which were interpreted for single groups of gestational age and diagnosis. A questionnaire of the patients joined with this study, referring to the acceptance of cardiotocography, definitely voted for the telemetrical method. As to the valuation of the cardiotocograms (CTGs), it was necessary to consider a slight restriction of the undulation of the foetal heart rate by telemetry. Referring to the technical quality of the CTGs, the telemetrical method was inferior in all points while recording in recumbent position. Problems appeared to occur especially with adipose gravidas. In patients with toxaemia, we noticed a tendency to increasing systolic blood pressure combined with growing restriction of foetal undulation by telemetrical recording. The use of external telemetry with maternal ambulation at other diagnostical situations should depend only on technical quality and maternal acceptance of telemetry, since there are no differences with respect to information.


[Is diagnosis of toxoplasmosis within the scope of prenatal care meaningful?]. In the course of prenatal care, the sera from 5670 pregnant women were investigated. The average infection rate in the population was 39.22%; 60.39% were seronegative. To minimise the risk involved in toxoplasmosis infection, toxoplasma-antibodies must be definitely determined during prenatal care. This should be carried out simultaneously with the determination of antibodies to the rubella virus.


[Miscarriage in the first trimester--a "non-event"? An empirical study of 40 women and their physicians of experiences and coping]. Explored by structured dialogue, miscarriage meant for 31 women, a psychosocial stress but not a medical stress. They tried to convince themselves of the non-normative event via subjective causal attributions to obtain cognitive control. Social support, especially by the partner, minimising the importance of the miscarriage, and social comparisons were the main modes of coping with their problem. Doctors and nurses significantly undervalued the degree of psychosocial stress, which resulted in negative consequences in the doctor-patient-relationship.


[Results of treatment in vulvar cancer from 1970 to 1990]. From 1970-1990, 159 patients with invasive malignant tumours of the vulva (150 squamous cell carcinomas) underwent surgery at the University Hospitals, department of gynaecology. Heidelberg (1970-1988) and Homburg/Saar (1988-1990). 73% of the patients were more than 60 years old and 3% were less than 40 years old. The mean age was 69 years. 30% of the patients had diabetes mellitus. As a standard therapy, 101 patients had radical vulvectomy with bilateral inguinal node removal in accordance with S. Way. If nodes were found to be positive, the inguinal/pelvic region was irradiated postsurgically with 40-50 Gy. The 5 years survival rate for all patients with vulvar carcinoma was 69%. For early stage carcinomas (pT1, depth of invasion < or = 1 mm) a restricted radical therapy should be considered. 9 patients with early stage carcinomas survived disease-free for a period of 70 months. Significant prognostic differences were noticed if node histology was N- as opposed to N+ (p < 0.001), if depth of invasion was < or = 1 mm as opposed to > 10 mm (p < 0.001), if stage was pT1 as opposed to pT2 to pT4 (p < 0.001) or if lymphangiosis carcinomatosa (p < 0.01) was present or not. Prognostic differences were also noticed, if cytological grading was done in accordance with Broders (p < 0.09). 27 patients had successful reconstructive surgery with local cutaneous or myocutaneous flaps at the time of initial surgery. The median recovery period after radical vulvectomy with bilateral inguinal lymph node excision was 22 days. The median recovery period after radical vulvectomy with bilateral node removal and reconstructive surgery was 25 days. Early recurrence of carcinoma (< or = 6 months after initial therapy) was 5.9%, late recurrence was 12%.


[Cytogenetic subtyping of 139 uterine leiomyoma]. A cytogenetic study of 139 uterine leiomyomas of 70 patients is presented. 26 of the tumours failed to grow, 87 showed an apparently normal karyotype and 26 tumours were characterised by clonal aberrations. In 5 tumours, a numerical change was the only abnormality, including 2 tumours with a trisomy 12. 5 myomas showed an interstitial deletion of the long arm of chromosome 7. The largest group were 9 tumours with an aberration involving chromosome 12 in the band of 14-15. 2 myomas showed a t(12; 14) as the only abnormality, in 4 tumours very complex rearrangements with up to 12 breakpoints were observed. In the last group 7 myomas with other clonal aberrations involving 11 different chromosomes were found.


[Total ablation of uterine mucosa (TUMA)--C*U*R*T* instead of endometrium ablation]. Hysteroscopic ablatio endometrii, a procedure established in gynaecology as a result of the general trend to minimal invasive surgery, is clinically not very satisfactory. A new procedure, namely, transvaginal pelviscopically monitored cervix/cavum uteri fundus punch via C*U*R*T* (Calibrated Uterine Resection Tool) enables removal of the total endothelium from the uterus. TUMM (total uterine mucosa ablation) is a synthesis of pelviscopy, excoriation by conisation, and ablatio. This procedure may be considered as the presently optimal method to avoid hysterectomy in case of special indications.


[Early premature rupture of fetal membranes and risk of lung hypoplasia in the fetus. Case report from the 22d week of pregnancy with delivery in the 30th week of pregnancy]. We report on a case of ruptured foetal membranes in the 22nd week of pregnancy. A possible risk is pulmonary hypoplasia. Although factors exist that predispose to the occurrence of pulmonary hypoplasia, the diagnosis cannot be predicted prenatally. As pulmonary hypoplasia is associated with a high neonatal mortality rate, prenatal detection would be helpful in the clinical management of early premature rupture of the membranes.


[Infected chorionic hematoma as a cause of infection in the 2nd trimester]. Superinfected subchorionic haematomas are a rare septic focus in the 2nd trimenon. Symptoms being unspecific, the diagnosis has to be made by exclusion, in most cases. As the changes of a successful treatment of the manifest infection is poor, antibiotic prophylaxis as well as close laboratory controls and early antibiotic therapy should be discussed after sonographic diagnosis of an intrauterine haematoma. Two of our three patients reported on having suffered a miscarriage; only one pregnancy could be maintained after spontaneous depletion of the infected haemorrhage.


[Prenatal diagnosis of holoprosencephaly with postaxial polydactyly, cardiopathy with normal karyotype]. Holoprosencephaly is a malformation complex, in which the foetal forebrain (prosencephalon) fails to cleave. The aetiology of holoprosencephaly is heterogeneous. In the last years, a new malformation syndrome has been described, including holoprosencephaly, postaxial polydactyly, congenital heart defects and normal karyotype. In this report, a new case of this syndrome, prenatally diagnosed, is discussed, based on ultrasound and foetal blood sampling. The important implications are pointed out in relation to adequate genetic counselling.


[Activation of the processes of lipid peroxidation in the small-intestinal mucosa and liver in peritonitis and possible ways of their correction by a complex infusion-detoxification therapy]. Possibilities of lipid peroxidation (LPO) correction by infusion-detoxication therapy in peritonitis were studied in an experiment on 160 white rats and during clinical treatment of 88 patients with general peritonitis. It was shown that peritonitis development in rats was attended by an increase of LPO products--malonic dialdehyde and diene conjugates, in the hepatic tissue and small intestine mucosa, while the activity of antioxidant defense elements--superoxide dismutase and fat-soluble antioxidants, decreased. It was noted that LPO became normal after intravenous administration of exogenous superoxide dismutase (6 mg/kg) and the blood substitute Mafusol containing Krebs cycle substrate--sodium fumarate (9 ml/kg). Inclusion of Mafusol into the combined therapy of patients with general peritonitis contributed to the reduction of malonic dialdehyde and diene conjugate levels in the blood, normalization of its acid-base state, diminution of medium mass molecule content. Similar normalization of LPO was not recorded when lactosol was used. It has been concluded that blood substitute Mafusol used in the combined therapy of patients with general peritonitis significantly raises the treatment effectiveness.


[Indicators of central hemodynamics and microcirculation in patients with stenocardia for evaluation of the effectiveness of the treatment by plasmosorption]. The myocardial contractile function and microcirculation were studied in 39 patients with angina of effort, III-IV FC before and after plasmosorption course treatment in the presence of drug therapy. A positive clinical effect was recorded in 86% of cases that resulted in disappearance of anginal attacks, reduction of antianginal drug therapy in the presence of improved central hemodynamics and increased myocardial contractility and microcirculation.


[Effect of a synthetic prostacyclin analog on kidney function and the system of regulation of blood coagulation in experimental acute renal failure]. The influence of a stable analogue of prostacyclin on the renal function and parameters of hemostasis was investigated in experiments on animals with the nephrotic form of acute renal insufficiency. Diuresis, glomerular filtration, water and sodium reabsorption in the presence of diminished intravascular coagulation were recovered after two injections of the compound in a dose of 115 micrograms/kg.


[Phagocytic activity of the central macrophage of erythroblastic islet in experimental inhibition and stimulation of erythropoiesis]. Phagocytic activity of the erythroblastic island central macrophage (EICM) was studied under normal conditions and in experimental inhibition and stimulation of erythropoiesis. Specific phagocytic activity (SPA) was estimated by the amount of latex particles absorbed by 1 EICM during 30-min incubation on plastic Petri dishes. SPA of CM in all the animals (no matter what experimental model was chosen) depended on EI affiliation to a certain class, with the maximum activity in EICM of the III class. SPA in EICM of the II-III classes in polycythemia animals was low. Blood loss significantly increased SPA in EICM of the II-IV classes of maturity. EICM of the I class showed a lower SPA that was, probably, due to the involvement of immature monocytes into EI organization.


[Adverse effects of Ferrum Lec (clinico-experimental study)]. Summation of negative effects of hypoxia and lysosome-tropic properties of Ferrum Lec was observed in patients with severe stage of iron-deficiency anemia (IDA), and in rabbits with experimental IDA, during treatment by intravenous injections of Ferrum Lec. These effects were expressed in exageration of the destabilizing action of hypoxia on lysosome membranes, and attended by a significant rise in the lysosomal enzyme levels of blood plasma, by the development of dystrophic processes in hepatocytes, and by a decrease in the number of sinusoidal cells. All these facts should be considered in clinical practice.


[Effective and ineffective erythropoiesis in long-term hemorrhages]. The investigation of effective and ineffective erythropoiesis in long-term hemorrhages has shown that the index of normal erythroblasts maturation is decreased down to 0.7 +/- 0.01 (P < 0.01) that evidences disorders in the process of proliferation and differentiation of the erythron cells. A rise of ineffective erythropoiesis was observed at the level of polychromatophilic normal erythroblasts , the mean number of PAS (positive cells) comprised 22.9 +/- 4.1% (P < 0.05). Erythropoiesis intensity was lowered and erythrocyte life was shortened. The data obtained are important for the evaluation of the erythron system lesion and purposeful therapy.


[Effect of hematopoietic and lymphoid cells on the stromal CFU colony formation in rabbit bone marrow cell cultures]. Guinea pig and rabbit bone marrow and splenic cells with increasing cellular density suppress in vitro formation of fibroblast colonies by rabbit bone marrow clonogenic stromal cells. At the same time guinea pig bone marrow and splenic cells produce a stimulating effect on guinea pig bone marrow CFUf, but they are inhibited by rabbit splenocytes, although to a lesser extent than rabbit bone marrow CFUf. Rabbit blood platelets stimulate the growth of bone marrow CFUf of these animals. However, introduction into the culture of rabbit bone marrow cells combined with platelets eliminates the latter's growth-stimulating effect on stromal clonogenic cells of rabbit bone marrow. The results obtained have evidenced that guinea pig and rabbit bone marrow and lymphoid cell populations contain cells both stimulating and inhibiting CFUf proliferation, and that CFUf of varying animal species have different sensitivity to growth-stimulating and growth-inhibiting effects.


[Indicators of iron metabolism in pregnant women and infants]. Iron metabolism parameters were studied in pregnant women in time course of trimesters depending on the pregnancy character and in newborns and infants in relation to the antenatal period. The dynamic study of serum and erythrocytic ferritins has confirmed the expediency of iron therapy during pregnancy for prevention of iron deficiency in infants. Differences detected in the rate of using iron reserves by infants of the first year of life depending on the antenatal period character have necessitated an individual approach to preventive iron therapy.


Seasonal fluctuations of androgen-binding activity in the testis of the frog, Rana esculenta. An androgen-binding activity has been identified in nuclear extracts of the testis of the frog, Rana esculenta. A single class of high affinity (Kd = 2.5 +/- 0.6 x 10(-9) M), low-capacity binding sites was found. The binding was specific for androgens; 17 beta-estradiol displaced [3H]testosterone with an ID50 of 0.1 microM. Cytosolic binding activity has a low affinity and a high capacity and lacks specificity. The seasonal fluctuations in binding capacity did not correlate with the androgen peaks in plasma and testes between February and June and in September; periods coinciding with the resumption of spermatogenesis and the development of spermatids, respectively. The present data strongly support androgenic control of intratesticular function in vertebrates generally.


[New criteria for differential diagnosis of polycythemia vera and erythrocytosis]. "Laborskel-analyzer" (PSL-1) was used to estimate red blood cell volume for the differential diagnosis in 36 polycythemia vera, 20 erythrocytosis patients and 30 normal subjects. Erythrocyte count of polycythemia vera patients (I, IIA and IIB stages) showed a shift to the left (an increase of microcytic fractions), while erythrocyte count++ of 20 erythrocytosis patients (16 of them with a relative erythrocytosis and 4 with an absolute erythrocytosis) were close to erythrocyte count++ of normal subjects. The counting of the percent content of erythrocytic fractions of varying volumes has proved fraction 5 with the erythrocytic volume from 56 microns 3 to 62 microns 3 to have the highest information content. The percent content of this fraction in polycythemia vera fluctuated from 3.9 to 19.5%, and in erythrocytosis it was from 0.9 to 3.0%, that could serve as a criterion for the differential diagnosis of polycythemia vera and erythrocytosis.