Multicentre randomized clinical trial of inspiratory muscle training versus usual care before surgery for oesophageal cancer.

BACKGROUND: Up to 40 per cent of patients undergoing oesophagectomy develop pneumonia. The aim of this study was to assess whether preoperative inspiratory muscle training (IMT) reduces the rate of pneumonia after oesophagectomy. METHODS: Patients with oesophageal cancer were randomized to a home-based IMT programme before surgery or usual care. IMT included the use of a flow-resistive inspiratory loading device, and patients were instructed to train twice a day at high intensity (more than 60 per cent of maximum inspiratory muscle strength) for 2 weeks or longer until surgery. The primary outcome was postoperative pneumonia; secondary outcomes were inspiratory muscle function, lung function, postoperative complications, duration of mechanical ventilation, length of hospital stay and physical functioning. RESULTS: Postoperative pneumonia was diagnosed in 47 (39·2 per cent) of 120 patients in the IMT group and in 43 (35·5 per cent) of 121 patients in the control group (relative risk 1·10, 95 per cent c.i. 0·79 to 1·53; P = 0·561). There was no statistically significant difference in postoperative outcomes between the groups. Mean(s.d.) maximal inspiratory muscle strength increased from 76·2(26·4) to 89·0(29·4) cmH2 O (P < 0·001) in the intervention group and from 74·0(30·2) to 80·0(30·1) cmH2 O in the control group (P < 0·001). Preoperative inspiratory muscle endurance increased from 4 min 14 s to 7 min 17 s in the intervention group (P < 0·001) and from 4 min 20 s to 5 min 5 s in the control group (P = 0·007). The increases were highest in the intervention group (P < 0·050). CONCLUSION: Despite an increase in preoperative inspiratory muscle function, home-based preoperative IMT did not lead to a decreased rate of pneumonia after oesophagectomy. Registration number: NCT01893008 (https://www.clinicaltrials.gov).

[Attrition and poor performance in general practice training: age, competence and knowledge play a role]. / Uitval en stagnatie in de opleiding tot huisarts. Leeftijd, competenties en kennis spelen een rol.

OBJECTIVE: To investigate which determinants are related to poor performance and forced attrition in the first year residency in general practice (GP). DESIGN: Observational retrospective cohort study. METHOD: We collected data relating to personal characteristics such as age, sex and clinical experience from residents who started the GP training in Utrecht, the Netherlands, in the period March 2005-August 2007. We also collected competence scores from the domains 'medical expertise', 'doctor-patient communication' and 'professionalism', as well as scores on a national GP knowledge test. The outcome measures were 'poor performance' and 'forced attrition'. Multivariate logistic regression was used to analyse correlations between personal characteristics, competence scores on the 3 domains and knowledge scores in the first trimester on the one hand and poor performance or forced attrition on the other. RESULTS: 215 residents started the GP training. In the first trimester a quarter of the residents had an insufficient score in 1 or more of the domains. Competence scores were mutually correlated, but did not correlate with the knowledge score. 18 residents showed poor performance and 3 were forced to stop their training. Poor performance and forced attrition were correlated with age (adjusted odds ratio (OR): 1.1; 95% CI: 1.0-1.3), insufficient knowledge (adjusted OR: 8.9; 3.0-26.3) and medical expertise (adjusted OR: 2.1; 1.1-4.0) at the beginning of the training. CONCLUSION: Age, insufficient knowledge of general practice, and insufficient competence in the domain of 'medical expertise' at the beginning of the training are risk factors for poor performance by residents and attrition from their GP training.

A human monoclonal antibody inhibiting partially factor VIII activity reduces thrombus growth in baboons.

BACKGROUND: The inhibitory activity of an anti-factor VIII (FVIII) antibody can be modulated through glycosylation of the antigen binding site, as has recently been described. This offers the opportunity to develop an optimized anticoagulant agent targeting partial FVIII inhibition. OBJECTIVES: We investigated in non-human primates the antithrombotic activity, pharmacokinetics,and pharmacodynamics of a human monoclonal antibody, Mab-LE2E9Q, inhibiting FVIII activity partially. METHODS: The ability of Mab-LE2E9Q to prevent thrombosis was evaluated in baboons after administration of 1.25 and 5 mg kg(-1) antibody or saline as a single intravenous (i.v.) bolus. Thrombus development was recorded in expansion ('venous') and in Dacron ('arterial') thrombosis chambers incorporated in an extracorporeal arteriovenous shunt implanted between the femoral vessels 1 h, 24 h and 7 days after the administration of Mab-LE2E9Q. RESULTS: Mab-LE2E9Q reduced thrombus growth to a similar extend 1 h, 1 day and 1 week after administration of the antibody. Ex vivo pharmacodynamic analysis indicated that the evaluation of the residual FVIII activity was strongly dependent on the type of FVIII assay and on the phospholipid concentration in the assay. No significant difference in bleedings was observed between animals treated with Mab-LE2E9Q or with saline. CONCLUSIONS: Understanding the role of glycosylation in FVIII inhibition by a human monoclonal antibody allowed selection of an antibody inhibiting only moderately FVIII activity while significantly reducing thrombus development in a baboon extracorporeal model. As that antibody did not increase the bleeding tendency, it may represent a novel type of a long-acting antithrombotic agent with an optimal safety/efficacy profile.

Erectile dysfunction in primary care: prevalence and patient characteristics. The ENIGMA study.

The availability of adequate treatment for erectile dysfunction (ED) triggers studies into the prevalence of ED in the general population. Yet, previous studies showed different prevalence estimates partly due to differences in patient selection, in (unclear) definitions of ED and in assessment. ENIGMA has been designed to study the prevalence of ED in the general population of The Netherlands, using the WHO definition with a description of the way of assessment. In all, 5721 mail surveys were sent to all men, aged 18 y and older in 12 general practices in The Netherlands. A total of 5601 were included in the study and 2117 (38%) were completed. A total of 38% of the men reported to have ever had some kind of erectile problem. The prevalence of ED was 17% (6% mild, 4% moderate and 7% complete). Age, diabetes, cardiovascular diseases, penile disorders, irradiation in the pelvic region, relational problems, fear for failure, surmenage, medication use and regular consumption of alcohol were independently related to ED. Men with ED were less content with their (sexual) life and had less confidence in sexual performance. Presence of ED was negatively related to affected happiness in life. ED is commonly found in men and is related to age, medication, comorbidity and lifestyle factors. Men with ED perceive a lower quality of (sex)life. Doctors should be aware of the presence of ED and its consequences in patients.

Impact of various questionnaires on the prevalence of erectile dysfunction. The ENIGMA-study.

The prevalence estimates of erectile dysfunction (ED) vary considerably across studies. These differences may be attributed to used definitions of ED. Quantitative data on the effect of different definitions of ED on the prevalence are lacking, because precise information on the used definition and questionnaire is often absent. Aim of this study was to quantify the effect of using different questionnaires for ED on the prevalence estimates. In all, 5721 mail surveys on sexual problems and ED were sent to all men (aged >18 y) in 12 general practices in the middle of the Netherlands of which 2117 were completed. The questionnaire contained Enigma (WHO), International Index of Erectile Function (IIEF), Cologne Erectile Inventory (KEED) and one question (Boxmeer, Krimpen). The prevalence of ED based on the various questionnaires and the effect of these questionnaires on risk factor relationships was compared. IIEF gave the highest age specific and overall ED prevalence, KEED the lowest. The difference in prevalence was 16.8%. The agreement (kappa coefficient) between the various ED definitions varied from 0.52 (IIEF & KEED) to 0.95 (Enigma & Boxmeer). The number of risk factor relations were similar for the Dutch studies, reduced for the IIEF and KEED. This study provides evidence that differences in questionnaires to assess ED have a considerable effect on the (age specific) prevalence estimates and little on the risk factor relations. The number of questions of the survey appears not to be responsible for differences in the prevalence of ED and risk factor relations, however they affect the response rate. Uniform use is strongly recommended, since a 'golden standard' for ED assessment (by questionnaire) is lacking. A short questionnaire with one or two questions is recommended for example the one from the Boxmeer-study. These data may be used to adjust (age-specific) prevalence rates comparing ED prevalence in the open population across studies.

Organic contaminants and trace metals in flounder liver and sediment from the Amsterdam and Rotterdam harbours and off the Dutch coast.

Organic contaminants [polychlorinated biphenyls (PCBs), organochlorine pesticides (OCPs), polybrominated diphenylethers (PBDEs), nonylphenols], organotin compounds and trace metals (cadmium, chromium, mercury and zinc) were determined in flounder (Platichthys flesus) liver and sediment from the Amsterdam harbour (North Sea Canal) and Rotterdam harbour (Euromonding) and off the Dutch coast between the Amsterdam and Rotterdam harbour mouths in order to assess the level of contamination in these harbours and to study contamination gradients.

The effect of monoclonal anti-human-platelet antibodies on platelet kinetics in a baboon model: IgG subclass dependency.

We assessed the in vivo effect of six intact anti-human antiplatelet antibodies of two major IgG subclasses on platelet kinetics in baboons. Five of the six antibodies tested caused thrombocytopenia of varying degree when injected at a precalculated threshold value. An agglutinating IgG1 antibody (MA-8L4A12) caused a long-lasting, mild thrombocytopenia with a predominant uptake of radiolabelled platelets in the spleen, while the four IgG2 antibodies tested (MA-13G8E1, MA-2M5A6, MA-21K2E8 and MA-22M10) caused a severe, transient thrombocytopenia with uptake of platelets in the liver. Two of the IgG2 antibodies (MA-13G8E1 and MA-2M5A6) caused platelet activation and aggregation in vitro, whilst the other two did not elicit a platelet aggregation response. The platelet survival time was shortened with all five of the thrombocytopenia-inducing antibodies, while only one antibody (MA-2M5A6) had a significant effect on the bleeding time. This study indicates that the IgG subclasss may be a determining factor in the outcome of platelet sequestration in immune-induced thrombocytopenia.

Correlation among total lymphocyte count, absolute CD4+ count, and CD4+ percentage in a group of HIV-1-infected South African patients.

Depletion of CD4+ T cells is one of the hallmarks of progression of HIV-1 infection. However, measurement of the CD4+ T-cell count is expensive and often unavailable in less developed areas. Previous studies have suggested that the total lymphocyte count (TLC) can be used to predict a low absolute CD4+ T-cell count. To determine the relationship between TLC and CD4+ T-cell count in HIV-1-infected South African patients, 2777 HIV-1-seropositive patients visiting the Immunology clinic at the Pelonomi Hospital in Bloemfontein, South Africa from April 1991 to April 1997 were included in the study. In total, 3237 observations were used to determine sensitivity, specificity, and likelihood ratios, with 95% confidence intervals, of various cutpoints of the TLC to predict an absolute CD4+ T-cell count of <200 cells/mm3, CD4+ percentage <20%, and CD4+ percentage <15%. Spearman rank correlations were calculated between TLC and CD4+ T cells, CD4+ percentage and CD8+ T cells, as well as between CD4+ and CD8+ T cells. Results demonstrated that a TLC of 2 x 10(9)/L or less had a sensitivity of 90.3% to detect patients with a CD4+ T-cell count of <200 cells/mm3, but a specificity of only 53.7%. When the TLC cutoff value was lowered, specificity increased but sensitivity decreased. For the observations as a group, a correlation (r = 0.704) between CD4+ T-cell count and TLC was demonstrated, but if the patients were divided into three groups according to their CD4+ T-cell count, this correlation weakened considerably. Therefore, although TLC shows a correlation with CD4+ T-cell count, it is not a good predictor of the CD4+ T-cell count in this population and should preferably not be used in the clinical care of HIV/AIDS patients.

PIP: Measurement of CD4 T-cell counts to monitor progression of HIV-1 infection is expensive and often unavailable in developing countries. Previous studies have suggested that the total lymphocyte count (TLC) can be used to predict a low absolute CD4 T-cell count. This possibility was explored in a study of 2777 HIV-1-positive patients attending the immunology clinic at the Pelonomi Hospital in Bloemfontein, South Africa, in 1991-97. A total of 3237 paired observations were used to determine the sensitivity, specificity, and likelihood ratios of various TLC cutoff points to predict absolute CD4 T-cell counts. A TLC of 2x109/l or less had a sensitivity of 90.3% to detect patients with a CD4 T-cell count of less than 200 cells/cu. mm, but a specificity of only 53.7%. When the TLC cutoff value was lowered, specificity increased but sensitivity decreased. Overall, there was a correlation between CD4 T-cell count and TLC (r = 0.704); however, this correlation was weakened considerably when patients were stratified into three groups according to their CD4 T-cell count. These findings suggest that use of TLC to predict the CD4 T-cell count should not be used in the clinical care of HIV/AIDS patients. Rather, informed decision making based on the clinical condition and risk factors for developing opportunistic infections is recommended.

Immunoglobulin G sub-class concentrations in South African adults: ethnic differences and reference ranges.

Serum samples from healthy adult volunteers (n = 149) were selected at random from disputed paternity cases, laboratory staff and volunteers attending clinical trials. Total immunoglobulin G (IgG) and IgG sub-class (IgGSc) concentrations were determined by a radial immunodiffusion technique (RID). Standard statistical analyses were used to determine differences between groups. Reference ranges of IgGSc concentrations were calculated on the resultant groups of data. Total IgG and IgGSc concentrations in men and women of the same racial group were similar, except for IgG4 which was slightly higher in white males than in white females (median: 0.36 g/L vs 0.20 g/L respectively). IgGSc concentrations were higher in blacks than in whites (median values: IgG: 17.1 vs 12.1 g/L; IgG1: 11.1 vs 7.6 g/L; IgG2: 4.3 vs 3.2 g/L; IgG3: 1.2 vs 0.90 g/L respectively) with the exception of IgG4 which was similar in both groups (median: 0.29 g/L). It would appear that IgGSc values differ among the ethnic groups. Ethnicity must therefore be considered when calculating reference ranges. The reference ranges for the IgG sub-classes in the two ethnic groups are intended for use in our laboratory and in others in South Africa that use the RID technique.

Magnetic resonance imaging in alcoholic Korsakoff's syndrome: evidence for an association with alcoholic dementia.

A magnetic resonance imaging study of 19 alcoholic Korsakoff patients, 17 non-amnesic alcoholics and 23 non-alcoholic controls was undertaken. Several measures of ventricular size and interhemispheric area were significantly greater in the Korsakoff patients. Interhemispheric fissure size was greater in the non-amnesic alcoholics than the non-alcoholic controls. Cortical grey matter T1 values were essentially the same for the three groups, whereas the deep grey and the white matter T1 values for the Korsakoff patients were significantly greater than the non-alcoholic controls. These results indicate widespread cerebral atrophy in alcoholic Korsakoff patients, which is largely subcortical and does not develop independently of the diencephalic pathology. Alcoholic dementia may be a more severe form of alcoholic Korsakoff syndrome, aetiologically related to the nutritionally-induced diencephalic pathology, rather than the neurotoxic effects of alcohol on the cortex.

Vasopressin secretion and memory impairment in alcoholic Korsakoff's syndrome.

The response of arginine vasopressin (AVP) to an intravenous hypertonic saline infusion was investigated in 19 patients with alcoholic Korsakoff's syndrome, 17 non-amnesic alcoholics and 21 non-alcoholic controls. Compared with non-alcoholic controls the Korsakoff patients had elevated basal AVP levels and showed erratic fluctuation of AVP secretion, not related to changes in serum sodium levels. The non-amnesic alcoholics had a similar, but less severe derangement. Neuropsychological tests revealed significant correlations between basal AVP levels and memory performance in the non-amnesic alcoholics, raising the possibility of a common lesion--most likely in the diencephalon--for memory impairment and AVP dysregulation in chronic alcoholics.

Simulated patients in assessing consultation skills of trainees in general practice vocational training: a validity study.

Although simulated patients are increasingly used in medical education, little research has been carried out on their validity. Validity in this case defines the relationship between performance with a simulated patient and performance with a real patient. One of the objectives of this study was to determine the validity of the use of simulated patients in assessing the consultation skills of trainees in vocational training at the Department of General Practice, University of Utrecht, The Netherlands. A check-list with a rating scale was used to assess the consultation skills of trainees at the department with simulated patients as well as in their training practices with real patients. The simulated and the selected practice cases were patients with complex multi-conditional problems like low back pain, headache and chest pain. The consultation skills were subdivided into four groups: the patient-centered approach, the non-somatic approach, communication skills and interpersonal skills. The measurement of skills, in particular of consultation skills, is very difficult. A description is given of the way the research group solved this problem. The analysis was performed by determining the sensitivity and predictive value of the assessment of a simulated encounter with a routine practice encounter. A difference existed in the assessed level of consultation skills in the simulated encounter compared to the level in the training practice. In simulation the level of consultation skills was higher than in day-to-day practice. This difference can reflect the difference between competence and performance. Competence is defined as what a doctor is capable of doing and performance as what a doctor actually does in day-to-day practice.(ABSTRACT TRUNCATED AT 250 WORDS)

Clinical use of a portable electronic device to measure haematocrit.

A small portable device called the blood electrometer (BEM) was developed to assist clinicians to distinguish patients with extreme blood loss from those with normal packed cell volumes. Blood was collected in 5 ml lithium heparin tubes from 80 normal controls and 24 patients in an intensive care unit. BEM and accurate microcentrifugal techniques were compared. Intraclass correlation coefficients between the techniques of r = 0.96 and r = 0.93 were found in the normal controls and patients respectively. Because the BEM operates on the principle of conductivity, changes in some of the biochemical variables which could influence conductivity were investigated in the patients. Mean plasma total protein and albumin concentrations were lower compared with normal reference ranges. Six of the 24 patients were acidotic and 4 alkalotic. Leucocyte counts obtained randomly from 13 patients were elevated. Changes in measurements which could influence conductivity did not affect the BEM reading. We conclude that the portable BEM could be of great value in circumstances where a fixed power source is not available and rapid haematocrit measurements in a large number of patients are required.

Antithrombotic activity of Bay u3405, a thromboxane A2-antagonist, in patients with Dacron aortic grafts: a random controlled clinical trial.

Twelve patients with Dacron aortic grafts participated in a placebo controlled, crossover trial to investigate the effect of Bay u3405, a thromboxane A2 receptor antagonist, on graft thrombogenicity. During each treatment period (seven days, Bay u3405 or placebo), 111In-platelet survival and platelet deposition on the grafts were measured daily by gamma-camera imaging and blood radioactivity analysis. Bay u3405 substantially reduced the deposition of platelets and the thrombogenic index, while platelet survival remained unchanged. The ex vivo platelet aggregation response to ADP and epinephrine was significantly inhibited. The bleeding time increased slightly but not to any clinically relevant extent, and no adverse side effects were recorded. Bay u3405 seems to be a safe and effective drug for the inhibition of platelet deposition on aortic Dacron grafts. The use of quantitative imaging techniques is also more sensitive than the measurement of platelet survival for the assessment of antiplatelet drug efficacy in patients with aortic grafts.

Factors related to postpartum depression.

PIP: To determine which factors from a range of demographic, perinatal, psychosocial, and hormonal factors were related to postpartum depression, a sample of 81 women between 2 weeks and 6 months postpartum was divided into a depressed group (n = 22) and a nondepressed group (n = 59) by means of the Beck Depression Inventory as the main measure and the Visual Analogue Scale as an additional measure. A demographic questionnaire, a social support questionnaire, and a marital satisfaction questionnaire were completed by each subject. A depression incidence rate of 27.2% was found. There were significant differences between the depressed group and the nondepressed group in the area of social support, marital satisfaction, and premenstrual tension. No significant differences were found in age, parity, previous depressive episodes, cesarean births, or prematurity. It was concluded that psychosocial and hormonal factors played a more important role in postpartum depression than demographic and perinatal factors. (author's)^ieng

Comparison of oxine and tropolone methods for labeling human platelets with indium-111.

The effect of the chelates oxine and tropolone, used to label platelets, on the kinetics of indium-111-(111In) labeled platelets was studied in twelve normal human subjects. Autologous platelets were labeled either in saline with 111In-oxine or in plasma with 111In-tropolone. Mean platelet lifespan was estimated by fitting the disappearance curve of platelets from the circulation to the multiple hit and other mathematical models. The in vivo distribution of platelets was quantitatively imaged with a scintillation camera. The in vivo recovery of 111In-oxine and 111In-tropolone did not differ, and the mean platelet lifespan was also similar (111In-oxine: 230 +/- 29 hr; 111In-tropolone: 226 +/- 13 hr). At equilibrium (90 min after reinjection of labeled platelets) and at the end of platelet lifespan, 111In-oxine and 111In-tropolone radioactivities in the spleen and liver were similar. These results demonstrate that the results of kinetics measured with 111In-oxine or 111In-tropolone do not differ significantly.

Analysis of indium-111 platelet kinetics and imaging in patients with aortic grafts and abdominal aortic aneurysms.

To quantitatively characterize processes of platelet thrombus formation in vivo, the kinetics and incorporation into thrombus of autologous In-111-labeled platelets were compared in six patients with aortic aneurysms and in seven patients with prosthetic aortic grafts. Although platelet survival was comparably shortened in both patient groups (mean, 5.8 days), the maximum radioactivity (percentage of whole body radioactivity) as determined by gamma camera imaging was higher in the aneurysms than in the grafts (3.3% +/- 1.6% vs. 1.6% +/- 1.1%, p = 0.05). Maximum In-111 uptake was also attained more quickly in the aneurysm patients (2.3 +/- 0.8 days vs. 3.5 +/- 1.3 days; p = 0.07). The experimental platelet kinetic and imaging data were subsequently evaluated by compartmental analysis to estimate both normal and disease-related components of platelet destruction. This analysis indicated that deposited platelet radioactivity had a longer residence time on grafts (2.9 +/- 1.7 days vs. 1.4 +/- 0.9 days, p = 0.07) but accumulated at a faster rate in aneurysms (5.0% +/- 3.4% per day vs. 1.4% +/- 0.9% per day, p = 0.02). As determined by imaging, only a proportion of increased platelet destruction was specifically due to the aneurysms (55% +/- 38%) or grafts (17% +/- 11%, p = 0.03). This result indicates additional components of platelet destruction unrelated to graft and aneurysm thrombus formation which, in some graft patients, may reflect a greater severity of vascular disease or other mechanisms causing a preferential shortening of platelet survival. Thus, the analytical approach described may be a useful one for discriminating components of in vivo platelet utilization including platelet removal due to normal hemostatic and senescent mechanisms, localized thrombus formation, and more generalized vascular disease.

The association between peer consultations and three aspects of clinical competence.

The relationship between the clinical competence of general practitioners and the degree of peer consultation about diagnostic and therapeutic problems was studied. Three aspects of clinical competence are discerned: attention paid to somatic aspects, patient-orientation and risk of unnecessary harm of the management. Clinical competence has been measured by a written simulation of patient-doctor encounters using five patients and assessment procedures in a study with a correlational design. For this study 49 subjects were selected from a population of 184 GPs who completed their vocational training in general practice at the University of Utrecht between 1975 and 1980. They were selected from those who consult their colleagues frequently and systematically about a variety of patients' problems and from those who do so little or not at all. The 49 subjects did not differ from the remainder in several relevant aspects such as practice setting, subscription to medical journals, etc. The 49 GPs are relatively consistent in the quality of attention they pay to somatic aspects. The consistency with regard to the two other aspects is rather low, especially regarding the risk of unnecessary harm. Attention paid to somatic aspects is connected with patient orientation. The latter is also connected with risk of unnecessary harm, but the former is not. The three aspects are more or less separate aspects of clinical competence. Peer consultation has a direct relationship with quality of attention paid to somatic aspects; GPs who do not consult among peers anyway display a lower quality of attention to somatic aspects in comparison to those who do so.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of cell donor age on the synthetic properties of fibroblasts obtained from phenytoin-induced gingival hyperplasia.

Diploid fibroblasts obtained from explants of human gingiva and maintained in vitro undergo a several-fold decrease in protein and collagen synthesis as a function of increasing donor age. Using drug-induced gingival hyperplasia as a model, we performed experiments to learn whether fibroblasts derived from hyperplastic tissue behave in a similar manner. Fibroblast strains were established from explants of hyperplastic gingiva obtained from 10 patients chronically ingesting phenytoin and ranging in age from 9 to 45 years. Protein production and degradation were compared to previously reported data similarly obtained from periodontally normal donors ranging in age from 12 to 68 yr. The total quantity of protein and collagen produced by the phenytoin cells was significantly greater than previously reported for cells from normal gingiva. No donor age-related decrease in protein and collagen production nor in the proportion of cell synthetic activity committed to collagen production was observed for cultures of phenytoin cells. The gross pattern of proteins produced, as assessed by 2-dimensional gel electrophoresis, was unrelated to donor age in both normal and phenytoin cells, but three polypeptides ranging in size from about 20 kD to 40 kD that were not found in the cultures of normal cells were produced by five of seven phenytoin cells strains. The observations demonstrate that the phenytoin cells do not undergo the donor age-dependent decrease in synthesis observed for normal cells. This abnormality may account in part for the phenytoin-induced hyperplasia. The phenytoin cells appear to be a unique phenotype.