THERAPEUTIC STUDIES IN OSTEOPETROSIS

Four cases of osteopetrosis, with manifestations within the first months of life, are presented. The first two cases were siblings. One of them received no therapy, the other 12 blood transfusions and antibiotics. Therapy had no influence on the thrombocytopenia and haemolytic process in Case 2, and he developed rachitic-like changes and a decrease in serum calcium during hospitalization. Both these two siblings died at the age of 5 months. The last two cases have been on prednisone therapy for 21 and 14 months, respectively. Case 3 is now doing well on prednisone, 7.5–10 mg every other day. Her mental and stato-motoric development has so far been normal. Optic nerve decompression was performed in March 1968, and the eye on which the operation was performed still retains some vision. Case 4 was started on steroids when he was about 3 months older than Case 3. Splenectomy had to be performed due to high prednisone requirements, and he still needs prednisone, 15 mg every other day. He seems, unfortunately, to be blind and slightly retarded. Heparin seems to be of no practical value in this disorder. Cellulose phosphate therapy resulted in impaired calcium absorption. The resulting hypocalcemia seems, however, to have very little, if any, effect on the underlying disease.     

New Diagnostic Finding to Assess Para-Hisian Pacing Observed in a Patient with a Permanent Form of Junctional Reciprocating Tachycardia

Morphologic Change During Para-Hisian Pacing. Para-Hisian pacing, a useful method to differentiate conduction over an accessory pathway from conduction over the AV node, is assessed essentially by comparing the timing of local atrial electrograms between Hisbundle captured heats and His-bundle noncaptured heats. We describe the case of a patient with a permanent form of junctional reciprocating tachycardia, in whom an atrial double potential was recorded only during the tachycardia at the right posterior septum. During para-Hisian pacing, a morphologic change in the atrial electrogram at the posterior septum was also identified, as well as a change in the retrograde atrial sequence. Since the morphologic change of atrial electrograms during para-Hisian pacing cannot be demonstrated in a patient without an accessory pathway, this new finding could he considered a new additional diagnostic criterion suggesting the presence of an accessory pathway.     

DPP系列型多功能平板式自动包装机

该系列机运用机电一体化技术，将自动运料、加热、吹泡、装药、印字、热封、压痕、打批号、冲切、计数等，创新设计为全自动整机。适用于自动铝塑、塑塑、纸塑泡罩包装各种规格与形状的药品和医疗器械、电子元件、小五金等异形产品。     

症状评分、分度法诊断急性高原反应的应用与体会

本文报告应用症状评分、分度法对部队急进高原人群进行急性高原反应诊断的体会。现场调查结果;第1～3天发病率为18.5～37.9％,比临床症状学方法结果低。评分法具有量化、客观、简便等优点。对定量评价急性高原反应,指导临床与科研工作,使结果更具统一性和可比性,以及客观评价高原医学科研成果,具有理论和实际意义。     

A dissolution rate apparatus for the prediction of initial drug absorption patterns in beagles: Tolbutamide tablets

An apparatus utilizing liquid turbulence to simulate hydrodynamic conditions generated by gastrointestinal peristalsis was designed to estimate drug release from solid oral dosage forms. This turbulence was achieved through special arrangement of a pipetting pump to a dissolution chamber. By adjusting the flow rate of the pump to deliver and withdraw a fixed volume of dissolution medium per minute, a correlation was developed between dissolution rates and absorption patterns in beagles of two commercial tolbutamide tablets, A and B, and a micronized tolbutamide suspension. On the basis of this relationship, it was possible to predict the initial absorption patterns of two misformulated tablets, C and D.     

Effect of atorvastatin upon platelet activation in hypercholesterolemia, evaluated by flow cytometry

Hyperlipidemia is a well established risk factor for cardiovascular disease and atherothrombotic events, in which platelet activation also plays a significant role. However, very few studies have addressed platelet activation in hypercholesterolemia, the potential effect of lipid lowering drugs upon platelet hyperfunction, and the question of whether changes in the latter are correlated to normalization of plasma lipids. This study used whole blood flow cytometry to assess in vivo and in vitro platelet activation in a group of 33 patients with hypercholesterolemia, and also the ex vivo effect of atorvastatin (20 mg/day) upon such activation. A control group of 40 normolipidemic volunteers matched in terms of age, sex and added risk factors to the patient group was used. The results showed that hypercholesterolemic patients had in vivo a significantly greater percentage of GPIIb/IIIa- and phosphatidylserine-positive platelets compared with the control group (4.62+/-3.51% and 2.58+/-1.19% versus 2.73+/-1.08% and 1.54+/-0.68%, respectively). In vitro response of CD62 expression to thrombin was also greater in the patients than in the controls (92.51+/-6.00% versus 89.63+/-10.72%, p<0.05). Atorvastatin therapy normalized platelet hyperfunction in the patients studied and reduced GPIIb/IIIa response to ADP (from 82.65+/-6.43% to 75.84+/-4.89%, p<0.01). A significant correlation can be seen between such normalization and the decrease in plasma levels of total and LDL cholesterol.     

Meeting the Accreditation Council for Graduate Medical Education competencies using established residency training program assessment tools

BACKGROUND: Most existing residency evaluation tools were constructed to evaluate the Accreditation Council for Graduate Medical Education (ACGME) competencies. METHODS: Before ACGME's six competency based assessment requirements for resident performance were developed, we created a residency evaluation tool with 5 domains important to successful surgical resident performance. Reliability was determined after 6 months of use. Factor analysis assessed whether the evaluation tool was a construct-valid measure of the ACGME competencies. RESULTS: Three hundred forty-three evaluations for 36 surgical residents were tested. The original evaluation tool was highly reliable with an overall reliability of 0.97. Factor analysis defined 4 new combinations of questions analogous to 4 of the ACGME competencies: professionalism (reliability 0.95), patient care (reliability 0.93), medical knowledge (reliability 0.92), and communication (reliability 0.92). The new competency clusters were correlated with each other to a moderate degree. CONCLUSIONS: Our locally developed tool demonstrated high reliability and construct validity for 4 of 6 ACGME competencies. The correlation between factors suggests overlap between competencies.     

Use of the short form of King's Health Questionnaire to measure quality of life in patients with an overactive bladder

OBJECTIVE: To develop a short version of the King's Health Questionnaire (KHQ), as there is a practical need to have a shorter version to summarize the eight domain scores into fewer domains. PATIENTS AND METHODS: Data from 293 patients were obtained from a randomized, double-blind, placebo-controlled clinical trial in Japan of oxybutynin and tolterodine in patients with symptoms of an overactive bladder. The KHQ has two single-item and six multiple-item domains. To construct the short form of the KHQ one item was selected from the each of multiple-item domains, based on standardized structural coefficients estimated by confirmatory factor analysis (CFA) in a previous study. These six items include the domains: 'daily activities from role limitation', 'travel from physical limitation', 'social life from social limitation', 'family life from personal relationship', 'depressed from emotion' and 'tired from sleep and energy'. Based on the six selected items a series of psychometric analyses were conducted. RESULTS: Exploratory factor analysis (EFA) with promax rotation identified two factors 'limitation of daily life' (LDL) and mental health. LDL consisted of 'daily activities', 'travel' and 'social life', and mental health included 'family life', 'depressed' and 'tired'. Based on the results from the EFA, the second-order factor structure was tested by CFA. The model fitted the data well for both the male and female model. The KHQ short form showed excellent reliability with Cronbach's alpha coefficients for LDL and mental health for both genders. The domains in the short form were responsive to clinical efficacy variables, and had statistically significant sensitivity to change in the patients' perception of bladder condition in all domains. CONCLUSION: These analyses confirm the psychometric properties and clinical validity of the short-form KHQ, which appears to offer a practical, valid and reliable health-related quality-of-life instrument.     

Effects of enhancing mitochondrial oxidative phosphorylation with reducing equivalents and ubiquinone on 1-methyl-4-phenylpyridinium toxicity and complex I-IV damage in neuroblastoma cells

The effects of increasing mitochondrial oxidative phosphorylation (OXPHOS), by enhancing electron transport chain components, were evaluated on 1-methyl-4-phenylpyridinium (MPP+) toxicity in brain neuroblastoma cells. Although glucose is a direct energy source, ultimately nicotinamide and flavin reducing equivalents fuel ATP produced through OXPHOS. The findings indicate that cell respiration/mitochondrial O(2) consumption (MOC) (in cells not treated with MPP+) is not controlled by the supply of glucose, coenzyme Q(10) (Co-Q(10)), NADH+, NAD or nicotinic acid. In contrast, MOC in whole cells is highly regulated by the supply of flavins: riboflavin, flavin adenine dinucleotide (FAD) and flavin mononucleotide (FMN), where cell respiration reached up to 410% of controls. In isolated mitochondria, FAD and FMN drastically increased complex I rate of reaction (1300%) and (450%), respectively, having no effects on complex II or III. MPP+ reduced MOC in whole cells in a dose-dependent manner. In isolated mitochondria, MPP+ exerted mild inhibition at complex I, negligible effects on complexes II-III, and extensive inhibition of complex IV. Kinetic analysis of complex I revealed that MPP+ was competitive with NADH, and partially reversible by FAD and FMN. Co-Q(10) potentiated complex II ( approximately 200%), but not complex I or III. Despite positive influence of flavins and Co-Q(10) on complexes I-II function, neither protected against MPP+ toxicity, indicating inhibition of complex IV as the predominant target. The nicotinamides and glucose prevented MPP+ toxicity by fueling anaerobic glycolysis, evident by accumulation of lactate in the absence of MOC. The data also define a clear anomaly of neuroblastoma, indicating a preference for anaerobic conditions, and an adverse response to aerobic. An increase in CO(2), CO(2)/O(2) ratio, mitochondrial inhibition or O(2) deprivation was not directly toxic, but activated metabolism through glycolysis prompting depletion of glucose and starvation. In conclusion, the results of this study indicate that the mechanism of action for MPP+, involves the inhibition of complex I and and more specifically complex IV, leading to impaired OXPHOS and MOC. Moreover, flavin dervatives control the rate of complex I/cellular respiration and Co-Q10 augments complex II [corrected].     

One good turn deserves another: an event-related brain potential study of rotated mirror-normal letter discriminations

The time to decide if a letter is normal or backwards (mirror-reversed) increases as the letter is rotated away from the upright. It is widely accepted that this increase in time reflects the mental rotation of the stimulus to the upright orientation in order to determine the mirror-normal status of the stimulus. Although response times tend to be longer for mirrored stimuli than for normal stimuli, the difference is constant across orientation. Little work has been focused on why mirror-image stimuli produce longer response times than normal stimuli. This study examines the question of whether or not mirrored stimuli are rotated in the picture plane at the same time as normal stimuli, and if so, why response times to mirrored stimuli are longer than that for normal stimuli. Both the behavioural and electrophysiological findings suggest that the mirrored stimuli are not only rotated in the picture plane, but that they are subsequently rotated to the normal view. It is this additional rotation that produces, at least in part, the delayed response times for mirror-image stimuli.