Percutaneous internal jugular vein catheterization with double lumen for temporary hemodialysis: experience of 100 cases.

We studied a total of 100 patients (46 men, 54 women) with renal failure requiring hemodialysis therapy by using double lumen catheter for temporary vascular access through the internal jugular vein. Fifteen patients had acute renal failure and 85 patients had end stage renal disease (including 27 cases of DM nephropathy). The mean length of time the catheter was in situ was 18.7 +/- 11.1 days (2-67 days); the mean frequency of the hemodialysis performed through this access was 7.8 +/- 4.6 (1-27). Recirculation rate was 7.19 +/- 2.68% (3.2-10.7%). The blood flow during hemodialysis was 180-200 ml/min. There was no catheter related mortality. The most common complication was catheter related septicemia (4%). Local infection of the catheter entry site occurred in 3 cases. Inadequate blood flow was detected in 3 cases. Two episodes of arrhythmia (atrial premature contractions, short runs of ventricular tachycardia) developed during the first hemodialysis procedure. Hematoma due to accidental puncture of the carotid artery was noted in one case. Neither pneumothorax nor hemothorax was detected. Our experiences revealed that the percutaneous internal jugular vein catheterization with a double lumen catheter is a safe and efficient temporary vascular access for hemodialysis.


Primary myelodysplastic syndrome: an analysis of 56 patients.

A total of 56 patients were diagnosed as primary myelodysplastic syndrome (MDS) at Chang Gung Memorial Hospital, Kaohsiung from April 1986 to December 1991. The median age was 65 years with an equal sex ratio. All patients presented with anemia and 52% with pancytopenia. The overall median survival for the entire group was 7 months, in which the chronic myelomonocytic leukemia (CMMoL) was 7 months, and 4 months for each of the refractory anemia with excess of blasts (RAEB) or the refractory anemia with excess of blasts in transformation (RAEB-T), however, the median survival had not been reached at 27 months for refractory anemia (RA) and at 33 months for refractory anemia with ring sideroblasts (RARS). Low-does arabinosyl cytosine (Ara-C) was administered in 9 patients with RAEB and RAEB-T, but no survival benefit was noted. Infection, especially pneumonia, was the most common cause of death. In 61 febrile episodes with clinically suspected sepsis, 10 (17%) were documented to associate with bacteremia. Twelve patients (7 RAEB, 4 RAEB-T, and 1 CMMoL) evolved to acute myelogenous leukemia (AML), the median interval from diagnosis to evolution was 4.8 months. This series indicates that only two groups of FAB subtypes could be clearly separated in terms of morphological findings and clinical outcome; RA and RARS constitute a good prognostic group, whereas RAEB, CMMoL, and RAEB-T constitute a poor prognostic group.


Postmenopausal tuboovarian abscess.

Twenty postmenopausal women with tuboovarian abscess were surgically managed at CGMH during 1981 to 1991. Fever with lower abdominal pain were the most common symptoms and signs. Laboratory, sonographic & roentgenologic studies helped in detecting and in making a correct preoperative diagnosis of the origin of the inflammatory complex. Half of the patients had postmenopausal bleeding or discharge. Six tuboovarian abscesses were ruptured at the time of surgery and of these had prolonged hospitalization due to complications. Among the six complications, 2 suffered from intraoperative bowel injury, 2 had postoperative wound infection, 1 colonocutaneous fistula and 1 sigmoid stricture. Abdominal total hysterectomy was tried in all the cases but the surgical procedure was changed to subtotal hysterectomy in two and bilateral salpingo-oophorectomy in one. Septic condition and suspicion of ruptured abscess are indications for immediate operation. No major medical complication developed in the post-operative period. However, the early detection and treatment of unruptured tuboovarian abscess had less surgery related complications and had a shorter mean length of hospitalization.


[Analysis of treatment and results of periapical surgery].

The purpose of this investigation was to study the treatment results following periapical surgery at Taipei Chang Gung Memorial Hospital. From August 1984 to November 1990, 101 periapical surgery treatments were performed on 82 patients. A total of 40 patients with 47 teeth were reexamined more than one year after they had received periapical surgery. The observation period varied from 1 to 6 years. According to radiographic and clinical criteria, the treatment results were considered successful in 61.8% of the teeth, doubtful in 19.1%, and unsuccessful in 19.1%. Clinical signs and symptoms were present in 21.3% of the teeth, occurring significantly more after in teeth demonstrating radiographically unsatisfactory healing.


[The comparison of microleakage among three different dentin bonding agents in class V cavities].

The use of the etching technique and an enamel bonding agent may effectively reduce microleakage of the cavity wall. However, the reduction of marginal leakage relating to class V cavities, is still unsatisfactory according to the dental literature. Due to the structural difference between the dentin and the enamel, though many new dentin bonding agents have been developed lately, none of them work perfectly. In this experiment, the "silver staining technique" was used to investigate the degree of microleakage in class V resin restorations which were bonded with 3 different dentin bonding agents (Scotchbond, Scotchbond 2 and Denthesive). The sample consists of 21 caries free human molars which were divided into 3 groups: 1) Scotchbond v. s. Scotchbond 2, 2) Scotchbond v. s. Denthesive, 3) Scotchbond 2 v. s. Denthesive. Both buccal and lingual surfaces were prepared for class V cavities. The cavities were then filled with composite resin Silux, and immersed in 50% silver nitrate solution for 2 hours, and followed by washing with distilled water. After that these teeth were immersed in photodeveloping solution under the fluorescent light for 3 hours. On finishing, they were washed again, sectioned vertically into mesial and distal halves with a Isomet sectioner and put under a microscope and evaluated for the degree of microleakage with Dr. Going's method. On statistical analysis, the results of this study showed that the degree of microleakage was not significantly different among the 3 dentin bonding agents in class V resin restorations, either on the gingival wall or the occlusal wall.


[A complete denture rebasing method in two appointments].

During rebase of the complete dentures, the denture bases are used as the trays for making border molding and final impression. Both open--mouth and closed-mouth impression methods are certainly expected to change the relationship between acrylic teeth and denture base after impression procedures. The upper denture usually shifts forward and downward, as a result, the occlusal relationship and esthetics are both damaged. The purpose of this article was to introduce an effective method for rebasing complete dentures. Through utilizing (1) the interridge distance, (2) the distance between the upper edentulous ridge and the occlusal surface of the lower acrylic teeth, and (3) the interocclusal records obtained immediately after each impression, the displacement of denture base can be corrected accurately. In addition, the original occlusion and esthetics are able to be preserved.


Meconium peritonitis-antenatal diagnosis by ultrasound.

Meconium peritonitis is usually the result of prenatal bowel obstruction with subsequent perforation, then the contents spread into the peritoneal cavity, which results in a sterile inflammatory reaction. The incidence ranges from 1/1500 to 1/2000, if without prenatal diagnosis and planned postnatal treatment, the mortality rate is as high as 62%. We describe three children, two with surgically, one with autoptically confirmed meconium peritonitis. All had abnormally prenatal ultrasonographic examinations. The first fetus showed a large 10 x 11 cm intra-abdominal mass with floating echogenic substances inside and with an echogenic rim. The second showed increased echogenicity with dilated bowel in abdominal cavity in one of the twin, and the third had an intra-abdominal cyst with several echogenic bands inside, fetal ascites was also noted. It is remarkable that the ultrasonographic findings were different in the three children. Two of the three children survived postoperation, one died 3 hours later after induction out at 31 weeks of gestational age due to multiple congenital anomalies.


Carcinosarcoma of esophagus. Report of one case and review of the literature.

Esophageal carcinosarcoma is a rare malignant tumor. The tumor is composed of both carcinomatous and sarcomatous elements. The multiple designations of names such as pseudosarcoma, pseudosarcomatous carcinoma, polypoid carcinoma etc. reflect the controversy on the nature of sarcomatous component of this lesion. We report a case of carcinosarcoma of esophagus occurred in a 67 year old male with progressive dysphagia. Esophageal polypoid tumor was found by endoscopy and was resected by esophagectomy. Carcinosarcoma was proved by demonstrating both carcinomatous and sarcomatous components in the tumor. Immunohistochemical studies revealed positive keratin stain in the sarcomatous area and positive vimentin stain in the sarcomatous area. The tumor was reported to have a better prognosis than that of the squamous cell carcinoma of esophagus in the literatures, especially in the survival rate.


Retrograde jejunogastric intussusception caused by a jejunal polyp.

A 70-year-old male presented with epigastric pain, vomiting and upper gastrointestinal bleeding 11 years after a subtotal gastrectomy. Retrograde jejunogastric intussusception was diagnosed by endoscopy and barium meal study and finally confirmed by laparotomy. After reduction of the intussusception, a small polyp was found at 20 cm distal to the anastoma, which served as the leading point of intussusception. The pathophysiology and clinical manifestations of this disease were reviewed.


Penile fracture. Case report.

A male patient suffered from pain, bleeding and deformity of penis with immediate detumescence during reverse coitus. Early surgical repair of the ruptured corpora cavernosa achieved excellent functional results. We report a case of penile fracture and review the literature.


Measuring psychological outcomes following rehabilitation.

Recent literature leaves little doubt that people with disabilities experience depressive and adjustment disorders at a greater rate that those in the general population. Differences between rates detected in different studies, however, prompt researchers to explore the definition of depression as applied to people with a disability, and to challenge the long-held notions that everyone with a disability undergoes depression at one time or another as part of the process of adjustment to disability. The present study measures the two related, but theoretically distinct, constructs of depression and adjustment to disability in a sample of spinal cord injured adults interviewed at one, four and twelve months post-rehabilitation. On the basis of these data, a two-dimensional measurement model is empirically developed for psychological outcomes, with the two dimensions representing adjustment and depression. The measurement model is supported by data at all three time intervals and by a number of different analyses. These findings underline the importance of distinguishing between depression and adjustment both in clinical applications and in research.


An outcome measure to quantify passive stiffness of the ankle.

The primary aim of this research project was to develop a method to quantify a specific variable of neuromuscular function, passive stiffness of the ankle. It was then used to determine if values for the outcome measure varied with age and sex in a sample of elderly men and women between 55 and 85 years old. Subjects were screened for medical conditions contraindicative to testing, e.g. severe arthritis, other history of bone or muscle disorders, ankle fracture, neural disorder causing spasticity or contracture. A rotatable footplate which recorded position and resistive torque with a potentiometer and strain gauge, respectively, was linked to an electric, computer-controlled torque motor. Passive elastic stiffness, defined as the slope of the passive resistance curve at 10 degrees dorsiflexion (in N.m/degree), was greater in males, (p < .001), and increased with age (p = .002). There was a significant effect of age group on passive range of motion (ROM) values for ankle dorsiflexion (p < .001), but also a significant sex by age interaction (p = .001). Females showed a large drop from a mean of 19.3 degrees +/- 3.2 in the youngest group (55-60 yr) to 12.1 degrees +/- 5.5 in the 81 to 85 yr olds. Corresponding mean values for the middle-aged males were 15.4 degrees +/- 4.3 versus 13.1 degrees +/- 3.5 of dorsiflexion in the group of 81 to 85 yr old men. It was concluded that passive ROM of the ankle into dorsiflexion showed decreases in the elderly, which seemed to reflect less complaint tissue structures.


Clinical measures of shoulder subluxation: their reliability.

The purpose of this report is to describe the reliability of three clinical measures used to evaluate changes in shoulder subluxation. The three methods include measuring the subacromial space in fingers breadth, using calipers, or a plexiglass jig. Thirty-six patients with shoulder subluxation who had experienced a cerebrovascular accident were the subjects. Four occupational therapists with experience in stroke rehabilitation were divided into two teams of two therapists and rated the subjects independently. Each rater repeated her assessments on nine subjects to test intrarater agreement. Inter-rater agreement was assessed both between members of the same team (27 subjects per rater pair) and members of different teams (18 subjects per rater pair). The measure of reliability was the intraclass correlation coefficient (ICC2, 1) as derived from two-way analysis of variance. The highest intra-rater reliability was displayed by the finger breadth method, the second highest by the caliper method and the lowest by the plexiglass jig. The coefficients in the former two cases were always above .8. Using the jig only one rater achieved this level. Agreement between the two members of the same team were above .75 for the fingers and caliper methods, but less than this for the jig. Between members of different teams however, only the finger breadth method attained reliabilities above .7, and the plexiglass jig, in particular, showed very low reliability. These results demonstrate the difficulty of achieving consistent clinical measurement for a condition like shoulder subluxation.(ABSTRACT TRUNCATED AT 250 WORDS)


Balance control in the elderly: implications for clinical assessment and rehabilitation.

Deterioration of balance control system with age results in a higher incidence of falls. To assess the performance of the balance control system we need to select appropriate body posture and/or motion, decide on the type and level of perturbation and study the response using selected measures. The guidelines we should use to determine the task, perturbation and measures is the focus of this article. Our work on the elderly is used to provide support for the various criteria put forward. The tasks evaluated for stability should include specific postures and movements which are part of the normal repertoire and challenge the balance control system. Variety of perturbations are necessary to get insights into the working of the system. The level of perturbation that can be handled should be specified. The response measures should be able to identify deterioration in the system performance, provide diagnostic information and insights into how the system has adapted to the age-related changes. These guidelines are critical if balance tests are to be used for clinical assessment and rehabilitation.


Gross motor performance measure for children with cerebral palsy: study design and preliminary findings.

This project investigated the validity, reliability and responsiveness of the Gross Motor Performance Measure (GMPM). The GMPM was developed as an observational instrument to measure changes in quality of movement in children with cerebral palsy. Physical therapists from 3 children's treatment centres assessed 107 children with CP, 18 children with head injury and 33 non-disabled children. Assessments were conducted on 2 occasions, 4 to 6 months apart. The measurement protocol included assessment with the GMPM and the Gross Motor Function Measure (GMFM). Validity was tested by comparing changes in GMPM scores to parent and therapist independent ratings of the children's motor performance. Also, a sample (n = 30) of paired assessments was videotaped for 'masked' evaluation by therapists. Inter-rater, intra-rater and test-retest reliability studies (n = 30) were conducted. Responsiveness to change was determined through parent and therapist ratings of the importance of observed changes in quality of movement. Data collection for this study has just been completed. Validation hypotheses have been postulated regarding correlations between changes in GMPM scores; GMFM scores; age of children; diagnosis; severity of condition; parent, therapist and 'masked' evaluator judgement of change. Correlation analysis, t-test and analysis of variance results will be presented. Reliability data for the GMPM and parent/therapist rating scales will be presented using intra-class correlation coefficients. Data supporting responsiveness of the GMPM will be presented using an analysis of variance model for 'stable' and 'responsive' groups.


Spasticity measurement in stroke: a pilot study.

The ability to objectively measure spasticity, related to cerebral stroke, is important in the rehabilitation therapies since many therapeutic modalities have been developed over the years to reduce spasticity. The unproven clinical expectation is that function would be improved were spasticity to be reduced. Unfortunately, the ability to measure spasticity to conduct efficacy studies of spasticity-reducing therapies is not possible. This relates to the multi-variable nature of the spastic syndrome with the result that no clinical measurement technique has been proven to be sensitive, valid and reliable. Therefore, it is important to develop a research-oriented spasticity measurement system to meet this need. We describe the current development of such a system. Details of our pilot study of a reflex excitability technique, designed to measure certain components of cerebral spasticity, are presented. The technique combined biomechanical and electrophysiological measures to investigate a homogenous stroke sample (n = 6); it incorporated the H-reflex in soleus, during passive ankle movements, as a measure of faulty neural inhibition. This component significantly (p < .05) differentiated the stroke sample from a matched, healthy control group (n = 6). Evocation of a cutaneous reflex in soleus was a condition that was problematic and it had to be dropped from the protocol. Joint stiffness, which is thought to affect measures of spasticity during passive movement, did not contaminate the measures. Further research in this direction is required to delineate and measure other neural components of spasticity while taking into account related non-neural variables. The final objective in this line of research is to develop a valid, reliable and sensitive spasticity measurement system that could be used to judge the efficacy of physical neurorehabilitation treatments currently employed to reduce spasticity following stroke.


Construction and validation of the Alberta Infant Motor Scale (AIMS).

The Alberta Infant Motor Scale (AIMS), an observational assessment scale, was constructed to measure gross motor maturation in infants from birth through independent walking. Based upon the literature, 58 items were generated and organized into four positions: prone, supine, sitting and standing. Each item describes three aspects of motor performance--weight-bearing, posture and antigravity movements. Content validation of the instrument was accomplished through a mail survey of Canadian pediatric physical therapists and consultation with an international panel of experts. Five hundred and six infants, age-stratified from birth through 18 months, participated in the reliability and validity testing of the AIMS. In addition, 20 infants who were experiencing abnormal motor development and 50 infants at risk for motor disorders were assessed and compared with the results of the full-term sample. Results to be presented include: 1) test-retest and inter-rater reliability estimates; 2) correlations between the AIMS and the Bayley and Peabody motor scores; and 3) scaling of the items along the age continuum for normal motor development.


Incoordination in patients with hemiparesis.

Incoordination is frequently observed in patients following a cerebrovascular accident. Clinical electromyographic studies which have furthered our understanding of this motor impairment are reviewed, and possible underlying mechanisms are discussed. It is suggested that the lack of coordinated voluntary movement observed in hemiparetic patients may be due, in part, to an impaired regulation of spinal neurones. In the rehabilitation sciences, the need to assess the effectiveness of treatment as well as develop new approaches for the treatment of hemiparetic subjects will require the combined efforts of many investigators. A two-fold research approach is supported which aims: 1) to quantify the motor deficit, and 2) to extend our knowledge of the physiological mechanisms underlying the deficit. Such a general research approach could be of value to the study of other sensorimotor deficits.


Validation of prediction of kindergarten-age school-readiness scores of nondisabled survivors of moderate neonatal encephalopathy in term infants.

Outcome studies of nonmalformed term infants with neonatal encephalopathy associated with late fetal and/or early neonatal distress show those in the severe category die or become disabled; 18% in the moderate category become disabled and of the nondisabled, greater than 40% have school-readiness delay. Predictive indices for kindergarten-age learning ability obtained from obstetrical/neonatal and family/social data were developed for 71 nondisabled survivors of moderate neonatal encephalopathy born in 1974-79 (Cohort I). Predicted outcome was compared to actual outcome of a second cohort of neonates with the same diagnosis, born in 1982-86 (Cohort II); comparison groups for both cohorts were tested. School-readiness scores from Cohort II were similar to Cohort I and both were below respective comparison groups. Prediction for the nondelayed was 68% to 95%; for the delayed 7% to 29%, affected by the lower sample size available for this category. Predicted scores were within 0.5 SD of actual scores for 80% of not delayed children. Nondisabled survivors predicted to do very well can be discharged from follow-up; others with moderate or severe neonatal encephalopathy should receive ongoing assessment.


Measuring long-term outcome after traumatic brain injury.

We report the results of the first stage of development of an instrument to measure long-term functional outcome after traumatic brain injury. The instrument focuses on both the person with a disability and the impact on the family caregiver. We illustrate the early stages of instrument development, focusing on one approach to standardized reviewer feedback to evaluate content validity. The results of the pilot testing are discussed in terms of: purpose, instrument construction, and clinical utility. While the complete details of the instrument are not presented, example items are used as illustration. A number of methodological issues in instrument development in rehabilitation are described including the logistics of reviewer feedback, the use of family caregivers in instrument development and the reliability of self-report in brain-injured population.


Measuring balance in the elderly: validation of an instrument.

This study assessed the validity of the Balance Scale by examining: how Scale scores related to clinical judgements and self-perceptions of balance, laboratory measures of postural sway and external criteria reflecting balancing ability; if scores could predict falls in the elderly; and how they related to motor and functional performance in stroke patients. Elderly residents (N = 113) were assessed for functional performance and balance regularly over a nine-month period. Occurrence of falls was monitored for a year. Acute stroke patients (N = 70) were periodically rated for functional independence, motor performance and balance for over three months. Thirty-one elderly subjects were assessed by clinical and laboratory indicators reflecting balancing ability. The Scale correlated moderately with caregiver ratings, self-ratings and laboratory measures of sway. Differences in mean Scale scores were consistent with the use of mobility aids by elderly residents and differentiated stroke patients by location of follow-up. Balance scores predicted the occurrence of multiple falls among elderly residents and were strongly correlated with functional and motor performance in stroke patients.


[Abandonment, therapeutic relentlessness or euthanasia].

Which standards and values should guide our conduct relating to death and palliative care? Who, in the end, has the right to decide whether or not to administer a life extending therapy to terminally-ill patients? Where exactly is the border between an ordinary treatment and an extraordinary or a relentless one? Should euthanasia be legalized or not? These are some of the basic questions caregivers and health professionals who work with the dying are now asking themselves. To delve deeper into these questions and help to find the answers, the author draws a collective typology of the main ideas people have on these problems. The differences between the various trends of thinking regarding death are explained. The author concludes with a plea in favor of the principle where the dying patient becomes the centre of the end of life and agony process. Therefore, it is the caregiver's responsibility to grant the patient the right to be informed, to ask for or refuse therapeutic relentlessness, or to die with dignity and serenity.


[Snow-white in danger. Women, socialization and health. Some messages, by means of allegory].

This is the modern-day allegory of Snow White, the most beautiful woman in the kingdom. Because of her beauty she is banished from the castle. The seven dwarfs who befriend her welcome her into their cottage. Little by little, they begin to impose their demands on her. They try to coerce her into submitting to life's little demands in order to attain beauty, health and happiness. Diet categorizes the foods filled with nasty calories that Snow White must learn to do without. Fitness outlines her spare time exercise regimen to keep her slim and trim. Mr. Clean provides her with specific household cleaning tips. Job tips advise her how to get a job outside the home to maintain her financial autonomy. Pills provide her with a way to assure a smooth transition between work and the household chores. Oh! And we almost forgot Baby. Who will care for Baby? Snow White of course--since she is the only woman in the house. Finally, to assure perfect co-ordination of all these tasks, Excel sends her off to take a time management course. Snow white responds enthusiastically to all the expectations. As anticipated, she loses weight. She then becomes exhausted and collapses and is transformed into Burnt-Out Beauty. She remains in a deep sleep for 100 days and nights. The dwarfs place her in a glass box in a forest clearing where she is discovered by Prince Conscience. He opens the glass box, kisses her lightly on the forehead, and immediately disappears. Snow White awakens and remembers the events preceding her deep sleep.(ABSTRACT TRUNCATED AT 250 WORDS)


Three-dimensional reconstruction of skeletal muscle from MRI.

Three-dimensional (3D) reconstructions of medical images can provide useful information to the radiologist, enabling delineation and spatial correlation of anatomic structures in one image rather than consecutive two-dimensional (2D) images. Magnetic resonance imaging (MRI) is known to be a powerful technique for evaluation of skeletal muscle pathology and physiology. We investigated the role of 3D reconstruction from MRI images of pathological and healthy muscle, using volume rendering. The ability to easily delineate and recognize normal and injured muscle in the 3D images were dependent upon the original contrast between normal and injured muscle, spatial resolution, and anatomic complexity in the original slices, and also on imaging parameters such as volume averaging.


CT appearances in macronodular hepatosplenic tuberculosis: a review with five additional new cases.

Pseudotumoral or macronodular hepatosplenic tuberculosis (HSTB) is rare. Only 31 cases have been documented in imaging literature so far. Presented is the clinico-imaging review with five additional new cases of this uncommon variety. Due to nonspecific wide spectrum of imaging appearances, biopsy is mandatory in almost all cases. Clinical recovery and resolution of lesions on imaging may not be directly proportional.


The preparation of intermediates for the synthesis of 1D-myo-inositol 1,4,5-trisphosphate, a second messenger for signal transduction in cells.

Racemic 1,2,4-tri-O-benzyl-5,6-O-isopropylidene-myo-inositol was prepared by a new route involving crotyl (but-2-enyl) ethers and converted into the (-)-omega-camphanates to give the pure crystalline 1L-diastereoisomer and the chirally impure, syrupy 1D-diastereoisomer. The latter was converted via the 1-O-allyl or 1-O-p-methoxybenzyl ethers into chirally pure 1D-2,3,6-tri-O-benzyl-myo-inositol [required as an intermediate for the synthesis of 1D-myo-inositol 1,4,5-trisphosphate (1,4,5-IP3)], which was also prepared by de-p-methoxybenzylation of 1D-2,3,6-tri-O-benzyl-1,5-di-O-p-methoxybenzyl-myo-inositol. Racemic 2,4-di-O-benzyl-5,6-O-isopropylidene-1-O-p-methoxybenzyl-myo-inositol was prepared in a similar way to the analogous tribenzyl ether (using crotyl ethers) and the omega-camphanate esters behaved similarly, allowing efficient resolution by crystallisation of the (-)- and (+)-omega-camphanates. Racemic 1,2,4-tri-O-allyl-3-O-(but-2-enyl)-myo-inositol was resolved via the (-)-omega-camphanates and was also converted into 1,2,4-tri-O-(cis-prop-1-enyl)-myo-inositol, an alternative intermediate for the synthesis of 1,4,5-IP3.


Combining evidence from multiple imaging modalities: a feature-analysis method.

This study was designed to develop methods to improve radiologists' ability to detect and diagnose breast cancer. We evaluated the ability of a feature-analysis method to help radiologists merge judgements constructively from two rather disparate breast imaging tests. To accomplish these goals, we developed a list of perceptual features and quantitated the importance of each in the diagnosis of patients having both diaphanography (Test 1) and mammography (Test 2). Then, two decision aids were developed: One was a checklist of the critical diagnostic visual features from both tests that also assisted readers in rating these features numerically. The second was a computer-based classifier that assisted readers in merging the assessments of the two tests into one overall diagnostic probability. The value of these aids was assessed by comparing radiologists' accuracy in reading a set of proven cases in their standard fashion with their accuracy when reading in an enhanced mode, utilizing the checklist and computer classifier. When Test 1 was read adjunctively with Test 2, use of the decision aids led to a significant improvement in accuracy (p = .013) over the unenhanced, combined readings. For Test 1 alone, the aids led to a significant improvement over its low level of unenhanced reading (p = .046). For Test 2 alone, the enhancements provided little gain in accuracy over an already high level of performance on the full case set (p = .081), although significant gains were realized on the most difficult ones. We conclude that methods to aid standardization and merging of feature-based judgements can improve radiologists performance on complex diagnostic tasks.


Synthesis and biological properties of 2-substituted myo-inositol 1,4,5-trisphosphate analogues directed toward affinity chromatography and photoaffinity labeling.

A series of myo-inositol 1,4,5-trisphosphate analogues with the 2-acyl substituents p-aminobenzoyl (7), p-azidobenzoyl (8), 4-(5-[2-(benzamido)ethyl]-2-hydroxyphenylazo)benzoyl (9), and cis,trans-4-aminocyclohexylcarbonyl (10) were synthesised and examined for their effects on the 5-phosphatase, the 3-kinase, the tritiated trisphosphate-binding activity, and the Ca(2+)-releasing activity. Each analogue inhibited the hydrolysis of D-[5-32P]Ins(1,4,5)P3 and the phosphorylation of D-[3H]Ins(1,4,5)P3, catalysed by erythrocyte ghosts and brain cytosol, respectively. The analogues acted as full agonists in releasing Ca2+ from permeabilised cells and also inhibited the binding of D-[3H]Ins(1,4,5)P3 to cerebellum microsomes. The analogues 7 and 10 were utilised for immobilisation of the trisphosphate on Sepharose and the subsequent affinity chromatography effected purification of the above proteins. A photoaffinity probe, the appendage of which acted as the photoaffinity probe as well as a non-radioactive molecular marker, was also derived from the analogue 7.


Synthesis of diacylglycerol analogues as potential second-messenger antagonists and inhibitors of protein kinase C.

A series of analogues of diacylglycerol has been prepared and tested as inhibitors of protein kinase C (PKC). The diketone analogues, 10-hydroxymethyl-8,13-eicosanedione (24), 10-acetoxymethyl-8,13-eicosanedione (25), and 10-methoxymethyl-8,13-eicosanedione (26) each inhibited PKC activated by 2-O-acetyl-1-O-oleoylglycerol. Compound 24 was the most effective inhibitor of the growth of MR4 and HT29 cells in culture, and 26 was more effective than 24 against HL60 cells.


Thrombosis of the IVC and azygous continuation of IVC by bronchogenic cancer: CT and MRI appearance.

The authors describe the computed tomography (CT) and magnetic resonance imaging (MRI) findings in a patient with thrombosis of the inferior vena cava (IVC) and azygous continuation of the IVC caused by bronchogenic carcinoma. CT has been touted as the modality of choice for mediastinal evaluation. MRI is presently considered to be the initial modality of choice for mediastinal vessel evaluation. MRI is noninvasive, there is no radiation dose to the patient, multiplanar imaging can be done, and there is no need for iodinated contrast material. The satisfactory evaluation of an individual patient may require the use of MRI and CT in a complementary fashion.


Synthesis of racemic 5-phosphonate analogues of myo-inositol 1,4,5-tris- and 1,3,4,5-tetrakis-phosphate.

(+/-)-2,3,6-Tri-O-benzyl-5-O-p-methoxybenzyl-myo-inositol and (+/-)-2,6-di-O-benzyl-5-O-p-methoxy-benzyl-myo-inositol, accessible readily from (+/-)-3,6-di-O-allyl-1,2-O-cyclohexylidene-myo-inositol, were phosphitylated with dibenzyl N,N-di-isopropylphosphoramidite, and the resulting phosphite triesters were oxidised with tert-butyl hydroperoxide to give the corresponding fully protected myo-inositol 1,4-bis- (12) and 1,3,4-tris-phosphate (13) derivatives. Cleavage of the p-methoxybenzyl group from 12 and 13, phosphonylation with bis[6-(trifluoromethyl)benzotriazol-1-yl] methylphosphonate or (difluoromethyl)phosphonic di(1,2,4-triazolide), followed by treatment in situ with benzyl alcohol, and then hydrogenolysis of the benzyl groups gave the 5-methylphosphonate and 5-[(difluoromethyl)phosphonate] analogues of myo-inositol 1,4,5-tris- and 1,3,4,5-tetrakis-phosphate. The 5-methylphosphonate analogue of myo-inositol 1,4,5-trisphosphate acted as a calcium antagonist in permeabilized human platelets.


Configurational MR characteristics of metastatic brain tumors.

Magnetic resonance (MR) characteristics of metastatic brain tumors (MBTs) were studied using 15 cases (13 males and 2 females whose ages ranged from 32-78 yr, with the mean age of 57.8 yr; 12 adenocarcinomas, 2 squamous-cell carcinomas, 2 large-cell carcinomas). Nine cases showed hypointensities and five showed isointensities on T1-weighted images. Six cases showed markedly hypo- or hypointensities, two showed isointensities, and six showed markedly hyper- or hyperintensities on T2-weighted images. One case was markedly hyperintense on both T1- and T2-weighted images. The decrease of the signal intensity on the T2-weighted image was the main MR characteristic. A hypointense peritumoral rim was seen in four of the six hyperintense tumors on T2-weighted images. There was no correlation between the signal intensity and the histological classification.


New tetherable derivatives of myo-inositol 2,4,5- and 1,3,4-trisphosphates.

(+/-)-myo-Inositol 1-(3-aminopropyl hydrogen phosphate) 3,4-bis(disodium phosphate) (5) and (+/-)-myo-inositol 2-(3-aminopropyl hydrogen phosphate) 4,5-bis(disodium phosphate) (11) have been synthesized by conventional procedures. Each derivative has been immobilized on a polymeric resin in order to give a bioaffinity matrix.


CNS changes in neuro-Behçet's disease: CT, MR, and SPECT findings.

CNS changes in three cases of neuro-Behçet's disease were observed by computed tomography (CT), magnetic resonance (MR) and single photon emission computed tomography (SPECT). The present study illustrates the reversibility of lesions in the brain stem with MR, while CT failed to show any abnormal findings in the region of the disease. We conclude that MR is a quite useful method to detect lesions in the brain stem and to evaluate the effects of treatment in neuro-Behçet's disease. SPECT is also an important method for the evaluation of dementia recognized in neuro-Behçet's disease.


Stereoselective synthesis of glycobiosyl phosphatidylinositol, a part structure of the glycosyl-phosphatidylinositol (GPI) anchor of Trypanosoma brucei.

O-alpha-D-Mannopyranosyl-(1-->4)-O-2-amino-2-deoxy-alpha-D-glucopyranosy l- (1-->6)-1D-myo-inositol 1-(1,2-di-O-myristoyl-sn-glycer-3-yl hydrogen phosphate), a part structure of the glycosyl-phosphatidylinositol (GPI) anchor of Trypanosoma brucei, was synthesised efficiently by the phosphonate approach. The glycobiosylinositol core was prepared in a stereocontrolled manner from 1D-2,3,4,5-tetra-O-benzyl-1-O-(4-methoxybenzyl)-myo-inositol, tert-butyldimethylsilyl 2-azido-3,6-di-O-benzyl-2-deoxy-alpha-D-glucopyranoside, and methyl 3,6-di-O-acetyl-2,6-di-O-benzyl-2-thio-alpha-D-mannopyranoside.


Building blocks for the synthesis of glycosyl-myo-inositols involved in the insulin intracellular signalling process.

Glycosylation of (+/- )-1-O-benzyl-2,3:5,6-di-O-isopropylidene-myo-inositol (4) with 6-O-acetyl-4-O-allyl-2-azido-3-O-benzyl-2-deoxy-beta-D-glucopyranosyl trichloroacetimidate (6) gave the 4-O-(2-amino-2-deoxy-alpha-D-glucopyranosyl)- myo-inositol derivative (9) as a mixture of diastereoisomers which could be resolved by chromatography. Likewise alpha-glycosylation of 4 with 6-O-acetyl-2-azido-3-O-benzoyl-2-deoxy-4-O-(2,3,4,6-tetra-O-acetyl-beta- D- galactopyranosyl)-D-glucopyranosyl trichloroacetimidate (10) gave the corresponding pseudotrisaccharide derivative 16 as a mixture of diastereomers which could be resolved partially by chromatography. alpha-Glycosylation of enantiomerically pure 2,3:5,6- (18) and 2,3:4,5-di-O-isopropylidene-1-O-menthoxycarbonyl-myo-inositol (19) with 3,4,6-tri-O-acetyl-2-azido-2-deoxy-D-glucopyranosyl trichloroacetimidate (20) gave the pseudodisaccharide derivatives 21 and 22, respectively. Likewise, alpha-glycosylation of 18 with 10 afforded a pseudotrisaccharide derivative (23).


Nicardipine in the prevention of migraine headaches.

The subjects, 104 patients who had experienced more than two migraine episodes per month during the previous 6 months, received 60 mg of nicardipine daily for 2 months in an uncontrolled, Phase-IV study. Eighty-nine patients (mean age, 40 years; 16 with and 73 without aura; 60 women) completed the treatment regimen. The patients' blood pressure did not change during treatment. The mean number of migraine attacks was reduced significantly from 6.7 per month during the 3 months before treatment to 4.0 per month during treatment. The number of severe attacks was also reduced significantly. The patients' subjective ratings of the frequency and intensity of the attacks and their need for analgesia were reduced significantly from before to after treatment. Side effects (flushing and shortness of breath) were reported by four patients. It is concluded that nicardipine is safe and effective in the prevention of migraine attacks.


Blood and urinary magnesium kinetics after oral magnesium supplements.

A study was conducted to compare the pharmacokinetic profile of three oral magnesium supplements--magnesium chloride solution, slow-release magnesium chloride tablets, and magnesium gluconate tablets--at 16 mmol/dose. Twelve healthy normomagnesemic subjects were evaluated during an initial baseline study, followed by three magnesium supplementation studies. Supplements were administered in a randomized, crossover fashion at weekly intervals. During each of the four trials, subjects followed the same routines and consumed identical diets. Magnesium concentrations were measured in urine samples collected from 0 to 4, 4 to 8, 8 to 12, and 12 to 24 hours. Intraleukocyte, total serum, and ultrafiltrable magnesium were measured in blood samples drawn at 0, 1, 2, 3, 4, 8, 12, and 24 hours. Compared with baseline, 24-hour urinary magnesium excretion significantly increased (P < 0.05) after the administration of the magnesium chloride solution and also increased after the administration of the other supplements, but the difference was not significant. The 24-hour areas under the curve (AUCs) for total serum, ultrafiltrable, and leukocyte magnesium were greater after the administration of each of the supplements when compared with baseline, although the differences were not statistically significant. Differences in delta AUCs (supplement AUC minus baseline AUC) for total magnesium, ultrafiltrable magnesium, and 24-hour urinary magnesium excretion were statistically different from zero or between supplements. Statistically significant differences (P < 0.05) in total serum, ultrafiltrable, and leukocyte magnesium concentrations were observed at various time points. These results suggest that there were no major differences in the overall effect of these supplements on total serum, ultrafiltrable, and leukocyte magnesium concentrations but do reveal differences in the time-concentration profiles in magnesium levels in blood and urine among the three supplement forms.


In vitro activity of several antimicrobial agents against genital mycoplasmas.

The increasing resistance of genital mycoplasmas to tetracyclines is a serious problem, since this group of antibiotics is one of the few that is effective against virtually all species of mycoplasmas. Tetracyclines are also used to treat many sexually transmitted diseases. In this study, we assessed the susceptibility of Mycoplasma hominis and Ureaplasma urealyticum to macrolides, tetracyclines, spectinomycin, and trospectomycin by the agar dilution method. For M hominis, trospectomycin was the most active agent. Spectinomycin, tetracycline, and doxycycline had comparable mycoplasmatic activity, and the macrolides were ineffective. Against U urealyticum, spectinomycin and trospectomycin were the most active drugs, and were at least twofold more active than the macrolides and tetracyclines.


Third-generation cephalosporins: a review.

Third-generation cephalosporins play a pivotal role in the management of infections because of their potent and broad-spectrum antimicrobial activity, proven clinical efficacy in a wide variety of infections, safety, and potential for cost savings. Selection of third-generation cephalosporins poses a dilemma, however, particularly for clinicians who view the six antibiotics within this class as interchangeable. Choice of drug should be based on antimicrobial spectrum and other factors such as lack of resistance development and cost considerations. This review focuses on the distinguishing features of the parenteral third-generation cephalosporins. Such differences suggest the need for retiring the convenient "generation" classification system for cephalosporins in favor of a system that encourages recognition of clinically important features of each agent in this diverse group of cephalosporin antibiotics.


Deposition of loosely bound and firmly bound fluorides on tooth enamel by an acidic gel containing fluorosilicate and monocalcium phosphate monohydrate.

The amounts of loosely bound fluoride (F) deposited on human enamel by 4-min and 2-hour treatments with either acidulated phosphate fluoride (APF) or a monocalcium phosphate monohydrate and sodium hexafluorosilicate (MCPM-SHFS)-containing gel were measured with the use of a constant-composition F washing method. Enamel biopsies conducted before treatment and after washing were used to determine the firmly bound F uptake. The results showed that the MCPM-SHFS treatments produced significantly more loosely bound F than did the APF treatments. The 4-min treatment with either APF or MCPM-SHFS did not produce significant firmly bound F deposition, but the 2-hour treatments did, with that produced by MCPM-SHFS being significantly greater. The MCPM-SHFS gel, which had the same F content as APF and which may be applied to the proximal tooth surfaces in vivo without the use of a tray, has the potential to be more efficacious than APF because it deposits greater amounts of both loosely bound and firmly bound F.


Comparative effects of simvastatin and lovastatin in patients with hypercholesterolemia. The Simvastatin and Lovastatin Multicenter Study Participants.

The efficacy, safety profile, and tolerability of the HMG-CoA reductase inhibitors simvastatin and lovastatin were compared in a multicenter, randomized, double-blind study in patients with moderate hypercholesterolemia. Commonly prescribed doses of these two drugs were used by 544 men and women, who followed an American Heart Association phase I diet during a 6-week baseline period and for the 24 weeks of active treatment. Simvastatin 10 mg and lovastatin 20 mg produced statistically significant reductions in total and low-density lipoprotein cholesterol (LDL-C). Patients receiving simvastatin 10 mg once daily and lovastatin 20 mg once daily experienced similar reductions in LDL-C and total cholesterol; however, simvastatin 20 mg was statistically superior to lovastatin 40 mg in decreasing these lipid fractions. For all treatment groups, increases in high-density lipoprotein cholesterol were inversely related to baseline levels. Moderate decreases in triglycerides occurred with all doses. Lipoprotein(a) levels, measured in a subset of patients, were similar before and after treatment. Both drugs were well tolerated.


Issues in drug-related performance impairment.

Performance impairment associated with alcohol, drugs, and medical disorders is of increasing concern to clinicians. Understanding and assessing performance impairment associated with a particular drug or condition is complex and requires careful, critical evaluation of the literature. Awareness of the issues involved enhances the ability of the clinician to assess risks for a given patient and of a given medical therapy. Important study variables are described that should be considered when evaluating the literature pertaining to performance impairment. The clinical relevance of the results of performance studies is also discussed.


Fluoride concentrations in unerupted fluorotic human enamel.

Unerupted fluorotic human enamel was obtained from teeth surgically removed from patients with dental fluorosis. Fluoride was measured in samples produced by serial acid etching from the surface to the interior of blocks of buccal and lingual enamel. The severity of fluorosis, according to the TF index, was determined from the macroscopic and microradiographic appearance of the specimens. The shape of the fluoride profiles was not affected by the degree of severity of fluorosis, but the fluoride concentrations increased with increasing severity of lesions. Fluoride concentrations were similar to those previously recorded in erupted fluorotic enamel and were not related to the length of time the teeth had been present in the jaws. It was concluded that the fluoride content of erupted fluorotic enamel represents fluoride acquired during tooth formation and that further uptake prior to eruption may be negligible.


Therapy for pharyngitis and tonsillitis caused by group A beta-hemolytic streptococci: a meta-analysis comparing the efficacy and safety of cefadroxil monohydrate versus oral penicillin V.

A meta-analysis was conducted to compare the efficacy and safety of oral cefadroxil monohydrate (30 mg/kg QD or 15 mg/kg BID) with that of oral penicillin V (8, 10, or 15 mg/kg BID, TID, or QID) in the treatment of group A beta-hemolytic streptococcal (GABHS) pharyngitis and tonsillitis treated for 10 days. A simple random effects model was used for combining the efficacy and safety results of nine comparative trials performed in the United States. A total of 1646 patients aged < or = 19 years were considered evaluable; 1406 patients were evaluable using revised bacteriologic criteria, and 1499 patients were considered fully evaluable for safety. The results demonstrate significantly better response rates (P < 0.05) with cefadroxil monohydrate than with penicillin V for overall cure (91.8% versus 81.3%), bacteriologic cure (92.6% versus 81.4%), and bacteriologic recurrence (4.2% versus 10.5%); clinical cure rates were statistically similar (90.5% versus 90.2%). Revised bacteriologic criteria analysis revealed bacteriologic cure rates of 95.8% versus 88.7% (P < 0.05) and bacteriologic recurrence rates of 4.9% versus 7.1% (P = NS) for cefadroxil monohydrate and penicillin V, respectively. Adverse events related to drug administration occurred infrequently and did not differ significantly between treatment groups (P > 0.05). Compliance with cefadroxil monohydrate was at least as good as with penicillin V. Penicillin is currently the drug of choice in the treatment of GABHS pharyngitis and tonsillitis. Based on the information described in this large meta-analysis, cefadroxil monohydrate is an excellent alternative to oral penicillin V in the treatment of GABHS pharyngitis and tonsillitis.


Combined effects of laser irradiation and chemical inhibitors on the dissolution of dental enamel.

It has previously been shown that the susceptibility of human teeth to acid dissolution can be reduced by the presence of various chemical agents in the dissolution medium or by pretreatment of the teeth with laser irradiation. Now synergism between these two approaches to improving acid resistance has been demonstrated. Extracted human teeth were irradiated with a continuous-wave carbon dioxide laser at a wavelength of 10.6 microns. Energy doses of either 65 or 130 J/cm2 given over periods of 2 or 4 s, respectively, were applied and the teeth subjected to a severe acid challenge (0.1 M acetate buffer, pH 4.5, no calcium or phosphate common ion present) for 24 h. Mineral loss was assessed by measurement of mineral density profiles with quantitative microradiography. Experiments were carried out in the presence or absence of three chemical inhibitors with distinctly different mechanisms of action: ethane-1-hydroxy-1, 1-diphosphonic acid, fluoride, and dodecylamine HCl. Laser irradiation alone was found to lead to increased resistance of the teeth to acid challenge, with the higher energy dose being more effective than the lower dose. Each of the chemical inhibitors was effective on both lased and unlased teeth, with the percent reduction of dissolution greater when the inhibitors were applied to teeth lased with an energy dose of 130 J/cm2 which were already more resistant to acid challenge than were unlased teeth or teeth lased with a dose of 65 J/cm2.(ABSTRACT TRUNCATED AT 250 WORDS)


Enamel and plaque fluoride following glass ionomer application in vivo.

Glass ionomer fillings have been suggested to act as a fluoride-releasing system in the mouth. The aim of the present study was to evaluate whether a glass ionomer slab applied on the enamel can increase the fluoride content of the enamel and plaque of adjacent teeth in real-life conditions with frequent exposure to fluoride from other sources. Twenty-five adults living in a town with fluoridated drinking water participated in the study. The initial enamel fluoride content on the buccal surface of the contralateral premolars was determined using the acid etch biopsy technique. A round glass ionomer slab was placed buccally on the first molar on a randomly chosen side of the mouth (test side). After 2 weeks, the enamel fluoride content of premolars on the test and control sides was again determined whilst avoiding the site of the first biopsy. In addition, one biopsy was made on a previously etched area. After 2 and 4 weeks, plaque was collected from three approximal surfaces both on the test and control side, and the total fluoride content of the plaque was analysed. There were no significant differences in the fluoride content of sound or etched enamel before and after placement of glass ionomer. The fluoride content of approximal plaque of teeth close to glass ionomer was not higher than that of the control teeth, either after 2 or 4 weeks. Using the present method, no increase in the fluoride level of teeth adjacent to glass ionomer could be demonstrated. This may be due to the masking effect of fluoride from other sources.


Effects of citicholine in subcortical dementia associated with Parkinson's disease assessed by quantified electroencephalography.

Two groups of patients with idiopathic Parkinson's disease underwent quantified electroencephalography (EEGq) using fast Fourier transfer to assess the effects of treatment with citicholine. Evidence of cortical cognitive impairment was seen in one group but not in the other. Certain parameters were established which enabled the two groups to be distinguished by examining specific EEGq indices. Specifically, differences were found in the overall potentials of the delta and alpha bands, in the alpha/theta index, in posterior activity, in the anteriorization index of the delta and alpha rhythms, and in the spatialization index of the alpha rhythm. The implications of these differences in the potential involvement of the frontal lobes in subcortical dementia in Parkinson's disease are discussed.


Fluoride release from three glass ionomer materials and the effects of varnishing with or without finishing.

The release rates of fluoride from discs made from three glass ionomer products, Miracle Mix (MM), Ketac-Silver (KS) and Ketac-Bond (KB), into artificial saliva for 3 weeks were determined. The discs were either not varnished, varnished or varnished and finished. The release rates were not proportional to the fluoride concentrations of the products and were ordered: MM > KB > KS. The rates declined sharply as a function of time regardless of the product or treatment. Varnishing the discs caused a reduction of 61-76% depending on the product. Finishing the varnished discs produced a significant increase in the fluoride release from MM but had no effect on the release from KS or KB. In a separate study with MM, it was determined that the release rate of fluoride was inversely proportional to the powder: liquid ratio used to prepare the discs.


Secondary caries in situ around fluoride-releasing light-curing composites: a quantitative model investigation on four materials with a fluoride content between 0 and 26 vol%.

In the literature, secondary caries around composite restorations is reported often. Fluoridated composites are therefore interesting materials because they might reduce or inhibit secondary caries. In this article an in situ model investigation is presented in which the effect of F-releasing composites on enamel demineralisation around an artificial gap of 200 microns width was quantified after 1 month. The fluoride content of the composites varied between 0 and 26 vol%. The beneficial effect of the fluoride released was larger in the gap than at the outer enamel surface. In the gap, all fluoridated composites reduced the enamel demineralisation statistically significantly with respect to the non-fluoridated control. Microradiography showed a reduction of lesion depth values of 27-45%, and a reduction of mineral loss values of 25-56%. At the outer enamel surface next to the artificial gap, a beneficial fluoridation effect was measurable only near the most fluoridated composite. The results indicate that fluoridated composites may play a role in the future prevention of secondary caries.


Noncariogenicity of erythritol as a substrate.

Erythritol is a sugar alcohol produced by Aureobasidium sp. from glucose. It is 75-80% as sweet as sucrose and is also nonhygroscopic. The aim of this study was to evaluate this sugar substitute from a cariological point of view. Erythritol was neither utilized as a substrate for the lactic acid production nor for plaque formation of mutans streptococci (serotypes a-h) and certain oral microorganisms. It was not utilized for water-insoluble glucan synthesis or cellular adherence by glucosyltransferase from Streptococcus mutans PS-14 (c) and Streptococcus sobrinus 6715 (g). Finally, a significantly lower caries score (3.1 +/- 0.5; mean +/- SEM) was observed in specific pathogen-free rats infected with S. sobrinus 6715 and fed with a diet containing 26% erythritol, as compared to control rats fed with a diet containing 26% sucrose (60.5 +/- 2.0). Also, rats provided a diet containing 56% erythritol chocolate (23.8% erythritol) and challenged with S. mutans PS-14 exhibited a significantly lower caries score (6.7 +/- 0.8) compared to the sucrose chocolate group (82.8 +/- 2.8). The main conclusion from this study is therefore that erythritol is a promising sugar substitute from a cariological point of view.


Pharmaceutical research and development.

Some aspects of pharmaceutical research and development (R&D) are reviewed. The viability of major pharmaceutical manufacturers depends on their research and thus they commit substantial resources to R&D programs. Major pharmaceutical manufacturers in the United States employ about 40,000 R&D personnel, and worldwide pharmaceutical R&D expenditures reached $24 billion in 1990. The pharmaceutical industry is one of the most profitable; however, increasing prices of their products are often associated with increasing R&D costs, ignoring the many positive attributes of R&D. The Council on Competitiveness has recently proposed reforms in the approval process for new drugs, including accelerated approval, external review, and international cooperation. These reforms would help to preserve an R&D capability and a relatively unregulated pharmaceutical industry. Pharmaceutical R&D has made many important contributions, including increased life expectancy, the internationally competitive position of the US industry, and a positive balance of trade. However, a misunderstanding of the role of R&D could encourage development of policies and legislation detrimental to pharmaceutical R&D.


Urinary fluoride excretion in children using potassium fluoride containing salt or sodium fluoride supplements.

With the introduction of fluoridated domestic salt in France in 1986, questions have arisen with respect to its efficacy in caries prevention. It has been of interest to compare the urinary excretion of fluoride in children who consume fluoridated salt to that in children who take fluoride tablets. Ninety-three schoolchildren, 10-14 years of age, participated in the study and were divided into four groups: group I consumed fluoridated salt with every meal; group II ate at a school restaurant once a day and consequently consumed fluoridated salt at only their evening meal, as fluoridated salt is not authorized for use in collective restaurants; group III consisted of children taking fluoride tablets (1.0 mg F/day) exclusively, and group IV did not receive any systemic administration of fluoride for prevention and constituted a low-fluoride control group. Total 24-hour urine samples were collected from all subjects. The average daily urinary flow rates varied from 0.51 to 0.68 ml/min, but showed no statistically significant differences among the groups. The average urinary fluoride concentrations were 0.60, 0.30, 0.99, and 0.28 mg/l, respectively, for groups I-IV. The mean 24-hour urinary fluoride concentrations and excretion rates for children who consumed fluoridated salt at all meals (group I) were not statistically different from those using tables (group III). There were also no statistically significant differences between groups II and IV. The differences between urinary fluoride concentrations and excretion rates of groups I and III, as compared with group IV, were statistically significant.


Evaluation of the cariogenic potential of the intense natural sweeteners stevioside and rebaudioside A.

Stevioside and rebaudioside A, two intense natural sweeteners, that are constituents of the South American plant Stevia rebaudiana, were tested for cariogenicity in albino Sprague-Dawley rats. Sixty rat pups colonized with Streptococcus sobrinus were divided into four groups and fed stevioside, rebaudioside A or sucrose added to basal diet 2000 as follows: group 1, 30% sucrose; group 2, 0.5% stevioside; group 3, 0.5% rebaudioside A, and group 4, no addition. All four groups were sacrificed after 5 weeks. S. sobrinus counts were made and caries was evaluated according to Keyes' technique. There were no differences in food and water intake and weight gains between the four groups. There were significant differences in sulcal caries scores (p < 0.02) and S. sobrinus counts (p < 0.05) between group 1 and the other three groups. There were no significant differences between the stevioside, rebaudioside A and no-addition groups. It was concluded that neither stevioside nor rebaudioside A is cariogenic under the conditions of this study.


Exposure to low levels of fluoride and dental caries in deciduous molars of Tanzanian children.

In general, the prevalence of caries in African children may be classified as low to very low. In order to reduce this level even further, methods including the practice of good oral hygiene and administration of fluoride, e.g. water fluoridation, have been suggested. In 1984, 1986 and 1988, a mixed-longitudinal study amongst schoolchildren was carried out in a rural and urban area of Tanzania. In the rural area, shallow wells had been constructed at different periods in time in eight villages since the late 1970s. The drinking water in three of the villages contained fluoride in the range of 0.5-0.8 ppm (fluoridated) and contained less than 0.4 ppm fluoride in the remaining five villages (non-fluoridated). These fluoride levels were disclosed to the authors only during the course of the study. Thus the data were reanalysed to investigate the effects of fluoride and length of fluoride exposure on caries experience in the deciduous dentition. The study was carried out amongst 522 7- and 8-year-olds. Fluoride tablets were not used and toothpaste was virtually unavailable. Three periods of fluoride exposure were identified, i.e. 3, 5 and 7 years. The outcome variable was the mean dmft score in deciduous molars whereas the explanatory variables were age, length of fluoride exposure and year of investigation. Nutrition was considered a co-variate. Analysis of co-variance revealed a fluoride effect (p = 0.0004). Regression analysis did not show significant relationships between the mean dmft score and the three periods of fluoride exposure.(ABSTRACT TRUNCATED AT 250 WORDS)


Location of dental erosion in a referred population.

The aim of the study reported here was to determine locations of dental erosion and whether or not it is possible to decide the cause of erosion from the location. One hundred and six patients with dental erosion, 54 men and 52 women, mean age of 33.6 years, were studied. Erosion was classified as one of three grades on buccal, lingual or occlusal/incisal surfaces. Dietary and gastric causes of erosion were identified by means of a questionnaire. Erosion was observed on all teeth, but was commonest on the upper incisors, canines and premolars, and severest on palatal surfaces. In both groups, in which erosion had gastric and dietary causes, there were cases of buccal, lingual and occlusal erosion, but the risk of lingual erosion was 1.9 times greater in the group in which erosion had a gastric cause than in the group in which erosion had a dietary cause. Our findings indicate, however, that the cause of dental erosion cannot reliably be identified by location of the lesion.


Caries incidence, mutans streptococci and lactobacilli in irradiated patients during a 12-month preventive programme using chlorhexidine and fluoride.

Radiotherapy (RT) near salivary glands results in changes in the oral flora in favour of cariogenic organisms and an increased susceptibility to caries. The aim of this study was to assess the effect of a 12-month preventive programme on caries incidence and on the levels of mutans streptococci (ms) and lactobacilli in tongue loop samples taken from patients before, during and after RT. The regime consisted of 2 x daily rinsing with 10 ml 0.2% chlorhexidine, diluted 1:1 with water, for 1 week before RT, during RT and for 4 weeks after RT. This was then substituted with a 0.05% NaF rinse daily. A saliva substitute containing 2 ppm F was used as required. Scaling was carried out before RT and dietary advice and oral hygiene instruction given. Appropriate radiographs were taken at baseline and after 6 and 12 months. Tongue loop samples for microbiology were taken in the middle and end of RT and subsequently at 6, 8, 12, 24, 40 and 52 weeks. Whenever levels of ms exceeded 2 x 10(5) cfu/ml sample, 1% chlorhexidine gel in custom-made applicator trays was applied by the subject for 5 min daily for 14 days. In 25 subjects completing the programme, there was a total of 3 new caries lesions after 12 months. Thirteen pre-existing enamel lesions were arrested. There were significant reductions (p < 0.005) in ms levels from baseline values during RT and 4 weeks after RT. There were no significant increases in ms levels throughout the study.(ABSTRACT TRUNCATED AT 250 WORDS)


Prevalence of clinically undetected and untreated molar occlusal dentine caries in adolescents on the Isle of Wight.

The prevalence of clinically undetected occlusal dentine caries was determined in a group of adolescents living on the Isle of Wight by comparing data from clinical and radiographic examinations carried out in 1987. 6.3% of maxillary molars and 12.9% of mandibular molars which had been designated as clinically sound showed dentine caries on radiographs. Comparison of the radiographic data from 1975 and 1987 showed that there were more sound and fewer filled occlusal surfaces in 1987, but more primary occlusal caries. Approximately 50% of subjects examined in both 1975 and 1987 had at least one molar tooth with primary and/or secondary caries in dentine on radiograph.


Models for coronal caries and root fragments in an elderly population.

A random sample of 809 dentate, home-dwelling people 65 years of age or older participated in a study to determine the prevalence of dental diseases in the elderly. Part of the study investigated the determinants of coronal caries and root fragments in these older adults. Using a wide array of potentially explanatory variables available, logistic regression models were developed to identify relationships between these variables and coronal caries and root fragments. The variables with the most explanatory power in the coronal caries model were the presence of decayed root surfaces, lower salivary flow rate, lack of regular dental care and an interaction variable including race and a perception of financial well-being. When a subsequent model was created that did not include decayed root surfaces or root fragments as potential explanatory variables, an additional variable relating to self-perception of mouth appearance emerged. The strongest variables in the model for root fragments were episodic (vs. regular) dental visits, presence of root caries, lack of replacement for lost teeth, high levels of Streptococcus mutans and number of teeth present in the mouth.


The effect of protease inhibitors, leupeptin and E64d, on differentiation of C2C12 myoblasts in tissue culture.

Intracellular calcium levels play an important role in myofibril disintegration and regeneration of muscle fibers. Earlier studies have shown that the calcium activated protease, calpain, is involved in the removal of Z-discs from myofibrils of striated muscle and the tripeptide-aldehyde, leupeptin, which is an inhibitor of calpain, inhibits this activity. In the present communication, we demonstrate that leupeptin and another calpain inhibitor, E64d, inhibit the fusion of mouse skeletal muscle C2C12 myoblasts to form multinucleated myotubes in tissue culture.


The levels of vascular smooth as well as skeletal muscle actin mRNAS differ substantially among both myoblast and fibroblast lines with different skeletal myogenic potentials.

Little is known about the factors which regulate vascular smooth muscle (vsm) actin gene expression during skeletal myogenesis in culture. We have therefore looked for differences in the levels of accumulation of vsm actin mRNA among six mouse cell lines differing in apparent myogenic potential or in the complement of myogenesis determination genes which they express: NIH 3T3 and 10T1/2 non-myogenic fibroblasts and four myogenic lines--3T3-MyoD1 and 10EMc11s, MyoD/myogenin expressing sublines of the fibroblast lines, derived by transfer into the parent lines of a MyoD cDNA expression construct; C2C12, which expresses all four known myogenesis determination genes; and BC3H1, which expresses myf-5, myogenin, little herculin, and no MyoD. In differentiated cells of all four myogenic lines, vsm actin mRNA was expressed at levels dramatically higher than in growth-arrested NIH 3T3 cells, consistent with expression of vsm actin mRNA as an intrinsic part of the skeletal myogenic program somehow directed by myogenesis determination gene products. Interestingly, however, the level of vsm actin mRNA in growth arrested C3H10T1/2 fibroblasts was also dramatically higher than that in NIH 3T3. In view of these findings, and of the relative ease with which 10T1/2 as opposed to NIH 3T3 cells can be converted to myogenic lines, we hypothesize that factors which can act to regulate vsm actin gene expression in the absence of myogenesis determination gene expression may also influence the skeletal myogenic potential of the cells in which they are found. Among the myogenic lines, the ratio of vsm to skm actin mRNA was highest in BC3H1 cells, raising the possibility that were these cells forced to express MyoD and/or more herculin, as do the other myogenic lines, the ratio would decrease. Thus both fibroblast and myogenic lines will be useful for investigating the mechanisms controlling skeletal myogenesis and vsm and skm actin gene expression during myogenesis.


Cassia alata and the preclinical search for therapeutic agents for the treatment of opportunistic infections in AIDS patients.

In our search for therapeutic agents from natural sources with potential for the treatment of opportunistic infections in patients afflicted with acquired immunodeficiency syndrome (AIDS), we investigated antibacterial and antifungal activities of water extracts of Cassia alata (C. alata). The extracts are traditionally used in Ivory Coast, West Africa to treat bacterial infections caused by Escherichia coli (E. coli), and fungal infections caused by Candida albicans (C. albicans) and dermatophytes. Our working hypothesis was that the extract contains active ingredient(s) which can be isolated, identified and developed into useful antimicrobial/antifungal agents for the treatment of opportunistic infections in patients with AIDS. We used the broth dilution and agar dilution methods. Specifically, we focused on E. coli and C. albicans and the effectiveness of the extracts was evaluated relative to those of standard antibacterial agent chloramphenicol and antifungal agent amphotericin B. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) for the water extract of C. alata against E. coli were 1.6 mg/ml and 60 mg/ml respectively; corresponding data for chloramphenicol were 2 ug/ml. Similarly, the MIC and minimum fungicidal concentration (MFC) for the extract against C. albicans were 0.39 mg/ml and 60 mg/ml in contrast to 0.58 ug/ml and 0.98 ug/ml for amphotericin B. From the dose-response curve plots, the extract had an IC50 of 31 mg/ml for E. coli and 28 mg/ml for C. albicans. The data suggest that C. alata extracts contain agent(s) which have therapeutic potential and might be useful if isolated and developed for the treatment of opportunistic infections of AIDS patients.


High level expression and purification of peptide methionine sulfoxide reductase in Escherichia coli.

The enzyme peptide methionine sulfoxide reductase catalyzes the conversion of methionine sulfoxide residues in proteins to methionine. The 636 nucleotide coding region of the peptide methionine sulfoxide reductase gene has been amplified from a genomic clone using the polymerase chain reaction and the product was subcloned into plasmid pGEX-2T downstream of the glutathione S-transferase gene under control of the tac promoter. Escherichia coli XL1-Blue cells transformed with this plasmid and induced with isopropylthio-beta-galactoside expressed high levels of the fusion protein. The protein was soluble and was purified to homogeneity by affinity binding to a glutathione-agarose resin followed by cleavage of the fusion protein with thrombin. Both the fusion protein and the purified peptide methionine sulfoxide reductase protein showed high peptide methionine sulfoxide reductase activity.


Invertebrate and vertebrate neuroimmune and autoimmunoregulatory commonalties involving opioid peptides.

1. Evidence for bidirectional interrelationships between the nervous system and immune systems of vertebrates and invertebrates involving opioid peptides is briefly discussed. 2. The involvement of opioid peptides in autoimmunoregulatory communication also is discussed. 3. The presence of mammalian interleukin-like (1 & 6) and tumor necrosis factor-like molecules in invertebrates is reviewed as well as an apparent cascading system for these signal molecules. 4. The significance of ACTH and MSH in cellular immunosuppression and autoimmunoregulation is discussed in the context of a potential role in schistosomiasis and human immunodeficiency virus actions. 5. The review concludes with the hypothesis that the mammalian immune system has its origin in the invertebrate immune/defense system given the many similarities noted in the review based on new knowledge about the more "primitive" system.


Reduction of the acetylcholine-induced K+ current in identified Aplysia neurons by human interleukin-1 and interleukin-2.

1. Effects of bath-applied recombinant human interleukin-1 (rhIL-1) and interleukin-2 (rhIL-2) on the acetylcholine (ACh)-induced K+ current recorded from identified neurons (R9 and R10) of Aplysia kurodai were investigated with voltage-clamp and pressure ejection techniques. 2. Bath-applied rhIL-1 and rhIL-2 (10-40 U/ml) reduced the ACh-induced current in the neurons without affecting the resting membrane conductance and holding current. 3. The suppressing effects of these cytokines on the current were completely reversible. 4. Heat-inactivated rhIL-1 and rhIL-2 were without effect. 5. These results suggest that the immunomodulators, IL-1 and IL-2, can modulate the ACh-induced response in the nervous system.


Thymocytes express a mRNA that is identical to hypothalamic luteinizing hormone-releasing hormone mRNA.

1. A luteinizing hormone-releasing hormone (LHRH)-like molecule produced by thymocytes is similar to hypothalamic LHRH in both bioactivity and antigenicity. 2. We determined whether this thymic LHRH is identical to or only homologous with hypothalamic LHRH by synthesizing and sequencing the cDNA of rat thymus LHRH. 3. The thymocyte and hypothalamic LHRH cDNAs are identical, indicating, that the amino acid sequences of LHRH produced in the hypothalamus and the immune system are also identical. 4. This is the first report showing conclusively that cell of the immune system transcribe the authentic mRNA for a hypothalamic releasing factor, LHRH.


Glial localization of interleukin-1 alpha in invertebrate ganglia.

1. Mytilus pedal ganglion contains a small population of glial cells that are immunopositive for interleukin-1 alpha. Positively stained fibers can also be seen in the neuropil of these sections. 2. The marine worm Nereis diversicolor also exhibits positive neural immunostaining for interleukin-1 alpha. 3. Both organisms contain hemocytes that contain immunoactivity for interleukin-1 alpha. The study suggests interleukin-1 alpha to be an ancient cytokine given its presence in organisms that evolved significantly earlier than mammals.


The macrophage-activating properties of growth hormone.

1. We compared the ability of growth hormone (GH) and a well-characterized macrophage-activating factor, interferon-gamma (IFN-gamma) to activate highly purified populations of alveolar macrophages. Both GH and IFN-gamma primed macrophages triggered with opsonized zymosan to secrete superoxide anion (O2-) in vitro, but IFN-gamma was effective at a 40-fold lower concentration. Antibody blocking studies demonstrated that the priming activity of GH was independent of IFN-gamma, and the activity of IFN-gamma was distinct from that of GH. 2. Both IFN-gamma and GH increased the capability of macrophages to kill Pasteurella multocida in vitro. 3. Hypophysectomized rats challenged with Salmonella typhimurium were significantly protected by injections of either GH or recombinant rat IFN-gamma in vivo compared to vehicle-treated controls, and the protective effect of GH was increased by incorporation into liposomes. 4. Insulin-like growth factor-I (IGF-I) also primed alveolar macrophages in vitro, which is consistent with the idea that the protective effects of GH in vivo might be mediated by augmenting the synthesis of IGF-I. These data support the concept of reciprocal systems of communication between the neuroendocrine and immune systems.


Evidence that basal secretion of relaxin by individual cultured large luteal cells is influenced by mobilization of intracellular calcium: analysis by a reverse hemolytic plaque assay.

Ca2+ redistribution from an intracellular site(s) is a key biochemical event associated with relaxin (RLX) secretion by large luteal cells (LLCs) of porcine origin. However, the functional significance of internal stores of Ca2+ to basal rates of RLX secretion is not well understood. In addition, the identity of the intracellular storage site(s) for Ca2+ within LLCs is not known, nor is it clear if all RLX-releasing LLCs are equally dependent on this pool. In the present study, release of RLX from 24 h cultured luteal cells derived from early pregnant swine was monitored by a reverse hemolytic plaque assay (RHPA). Incubation of cultures in the presence of graded concentrations of thapsigargin (1 nM-1 microM), a plant sesquiterpene lactone that inhibits endoplasmic reticulum Ca(2+)-ATPase and thereby increases cytosolic Ca2+ concentrations, resulted in a dose-related increase in basal RLX secretion. The stimulatory effect of thapsigargin on RLX production was not abrogated by culture in Ca(2+)-free medium. Suppression of Ca2+ release from the endoplasmic reticulum of LLCs, achieved by incubating monolayers in medium containing dantrolene (1-100 microM), resulted in dose-related inhibition of basal RLX release. Taken together, these results suggest that the endoplasmic reticulum serves as a major storage site for Ca2+ redistribution within LLCs and, furthermore, that mobilization from this site is functionally coupled to basal secretion of RLX.


Evidence for the presence of 7-hydroperoxycholest-5-en-3 beta-ol in oxidized human LDL.

Low density lipoprotein (LDL) cholesterol is known to be oxidized both in vitro and in vivo giving rise to oxygenated sterols. Conflicting results, however, have been reported concerning both the nature and the relative concentrations of these compounds in oxidized human LDL. We examined the extracts obtained from Cu(2+)-oxidized LDL. Thin layer chromatography analysis showed that the sterol mixture became more complex with reaction time. Analysis of the components by thin layer chromatography and mass spectrometry allowed to establish that 7 alpha- and 7 beta-hydroperoxycholest-5-en-3 beta-ol (7 alpha OOH and beta OOH) are largely prevalent among the oxysterols at early times of oxidation. These hydroperoxy derivatives have not been previously identified in oxidized LDL. The concentration of 7-hydroperoxycholest-5-en-3 beta-ol decreased with oxidation time with a concomitant increase of cholest-5-en-3 beta, 7 alpha-diol (7 alpha OH), cholest-5-en-3 beta, 7 beta-diol (7 beta OH), cholesta-3,5-dien-7-one (CD) and cholest-5-en-3 beta-ol-7-one (7CO). After 24 h of oxidation a minor component of the LDL sterols was cholestan-3 beta-ol-5,6-oxide (EP).


1,2-Dioleoylglycerol promotes calcium-induced fusion in phospholipid vesicles.

The effect of 1,2-dioleoyglycerol (1,2-DOG) on the promotion of Ca(2+)-induced fusion of phosphatidylserine/phosphatidylcholine (PS/PC) vesicles was studied. 1,2-DOG is able to induce the mixing of membrane lipids at concentrations of 10 mol% without mixing of vesicular contents. At concentrations of 20 mol% or higher, 1,2-DOG promotes fusion, lipid and content mixing, of LUV composed of an equimolar mixture of PS and PC, which otherwise are unable to fuse in the presence of Ca2+. Fusion was demonstrated by fluorescence assays monitoring mixing of aqueous vesicular contents and mixing of membrane lipids. Studies by Fourier transform infrared spectroscopy provided evidence for a fusion mechanism different to that of Ca(2+)-induced fusion of pure PS vesicles. Final equilibrium structures were characterized by 31P-NMR and freeze-fracture electron microscopy. Ca(2+)-induced fusion of 1,2-DOG containing vesicles is accompanied by the formation of isotropic structures which are shown to correspond to structures with lipidic particle morphology. The possible fusion mechanisms and implications are discussed.


Photoelectrochemistry of dyes in phospholipid liposome.

The systems consisting of phenosafranin or thionine dye in the presence of phospholipid liposome in aqueous solution generate photovoltage when studied in a photoelectrochemical cell. A possible mechanism of photovoltage generation suggests the photoinduced electron transfer from phospholipid to dye in liposome through charge-transfer (CT) interaction. In these dye-phospholipid systems, a good correlation between the photovoltage (Voc) determined by photoelectrochemical studies and the equilibrium constant (Kc) determined by spectrophotometric studies, confirms the mechanism.


On the mechanism of cholesterol interaction with apolipoproteins A-I and E.

It is shown that cholesterol may interact with some substances containing the guanidine group (guanidine itself, arginine, metformin and dodecylguanidine bromide) and with arginine-rich proteins--apoproteins A-I and E. In the latter case the interaction produces the formation of cholesterol-apoprotein complexes. Analysis of such complexes has shown that one apo A-I molecule binds 17-22 and one apo E molecule binds 30-35 sterol molecules, which approximately corresponds to the amount of arginine residues in these proteins. Formation of cholesterol-apoprotein complexes has been suggested to occur due to: (1) formation of hydrogen bond and/or ion-dipole interaction between cholesterol hydroxyl and guanidine groups of the apoprotein arginine residues and (2) hydrophobic interaction of the cholesterol aliphatic chain with nonpolar side chains of the amino acids occupying the third position from arginine in the protein molecule.


Influence of Ca2+ and ethanol on the aggregation and thermal phase behaviour of L-dihexadecylphosphatidylcholine liposomes.

The influence of Ca2+ and ethanol on vesicle aggregation and thermal phase behaviour of the diether lipid 1,2-dihexadecylphosphatidylcholine (DHPC) was studied by light absorbance and DSC. At temperatures below the pretransition the ethanol-injected vesicles of L-DHPC were rapidly aggregated by Ca2+. Upon raising the cation concentration a biphasic increase in aggregation saturating at an approximate [Ca2+]/[lipid] ratio of 1.5:1 was observed. Further increase in [Ca2+] up to [Ca2+]/[lipid] stoichiometries exceeding 2.5:1 led to the loss of aggregation. Removal of ethanol by dialysis abolished Ca(2+)-induced aggregation. Ethanol-injected vesicles of the ester-linked L-dipalmitoylphosphatidylcholine (L-DPPC) or the racemic DL-DHPC were not aggregated by Ca2+ thus indicating the importance of the absence of ester carbonyls as well as the stereochemical configuration of the lipid in determining the mode of interaction of DHPC with Ca2+. Differential scanning calorimetry of multilamellar liposomes of L-DHPC showed an increase by 8 degrees in the pretransition temperature Tp in the presence of 250 mM ethanol. Both with and without ethanol, increasing concentrations of Ca2+ corresponding to [Ca2+]/[lipid] ratios of 1:1 to 20:1 caused a gradual decrease in Tp and finally the disappearance of the pretransition. Concomitantly a slight elevation in Tm occurred. No principal differences were observed in the thermal phase behaviour of the L-isomer and racemic DL-DHPC.


A facile synthesis of 1-O-alkyl-2-(R)-hydroxypropane-3-phosphonocholine (lyso-phosphono-platelet activating factor).

The synthesis of 1-O-alkyl-2-(R)-hydroxypropane-3-phosphonocholine is described. An efficient alkylation procedure using (NaH/DMSO) catalysis is also described and applied to the synthetic scheme. The key intermediate 1-O-alkyl-2-(R)-O-benzyl-3-bromopropane was phosphonylated using tris(methylsilyl)phosphite; the resulting phosphonic acid was coupled to choline using trichloroacetonitrile/pyridine or triisopropylbenzenesulfonyl chloride/pyridine followed by catalytic hydrogenation to yield 1-O-alkyl-2(R)-hydroxypropane-3-phosphonocholine.


Detection of protein mediated glycosphingolipid clustering by the use of resonance energy transfer between fluorescent labelled lipids. A method established by applying the system ganglioside GM1 and cholera toxin B subunit.

Glycosphingolipids labelled in the ceramide moiety with 3-(p-(6-phenyl)-1,3,5-hexatrienyl)phenylpropionic acid (DPH) or 6-(4-nitrobenz-2-oxa-1,3-diazole-7-yl)aminohexanoic acid (NBD) were incorporated into small unilamellar lecithin liposomes. They were used in resonance energy transfer (RET) experiments between the donor fluorophore DPH and the acceptor NBD to study glycosphingolipid distribution. In pure lecithin liposomes the fluorescent derivatives of GM1, GA1, galactosylceramide and sulfatide behaved almost identically and Ca2+ ions (5 microM or 150 mM) did not influence their transfer efficiencies. But cholera toxin B subunit (CTB) specifically clustered GM1 and enhanced the transfer efficiency. This RET-based method facilitated determination of binding specificity, complex stoichiometry (CTB/GM1 = 1:5), halftime of complex formation (5 s), cooperativity in binding and had a maximal sensitivity at a liposome dotation rate of just 0.25 mol%. In contrast to this, anisotrophy of the fluorophores and the excimer to monomer ratio of pyrene-GM1 were not affected by CTB. This demonstrates the advantage of the presented technique in detection of protein mediated glycosphingolipid clustering.


Effect of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and its toxic metabolites on the physicochemical property of the liposomal membrane in relation to their cytochrome P-450 inhibition.

The effects of the neurotoxin MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) and its toxic metabolites MPDP+ (1-methyl-4-phenyl-2,3-dihydropyridinium) and MPP+ (1-methyl-4-phenylpyridinium) on liposomal membrane were assessed using fluorescence-polarization and carboxyfluorescein leakage studies as well as in biological membrane preparations. Of the three compounds, MPTP was found to cause the greatest perturbation of membrane followed by MPDP+ and then MPP+. The ability of the three toxins to inhibit cytochrome P-450 enzyme activity (a microsomal membrane-bound enzyme system) was also studied and their relative potency was again found to be MPTP > MPDP+ > MPP+. The changes in the physicochemical property of the liposomal membrane can be related to the ability of the neurotoxin's ability to inhibit cytochrome P-450 activity.


Aortic valve replacement in young patients: long-term follow-up.

Thirty-four young patients (28 male and 6 female) underwent aortic valve replacement between 1972 and 1988. Ages ranged from 11 to 20 years (mean 17.7 years). Including reimplantation in the follow-up period, 40 valves were implanted, among which were 17 (43%) St. Jude, 7 (16%) Bjork-Shiley, and 4 (10%) Carpentier-Edwards. Seven patients (18%) had tissue valve prostheses (4 Carpentier-Edwards, 3 Hancock valves). There was one hospital death (2.9%). Follow-up was obtained in 30 of the 33 hospital survivors, with a mean follow-up of 80 months. In the follow-up period, one patient (3%) had a major thromboembolic event and one patient (3%) had prosthetic valve endocarditis. Six patients (18%) required replacement of the implanted valve; three of these had received Hancock tissue valve prostheses. There were three late deaths, yielding 96% survival at 5 years and 84% at 10 years. Twenty-three of 30 survivors are currently New York Heart Association class I. Aortic valve replacement in young patients can be performed with low mortality and morbidity, and with excellent long-term results.


Transient osteoporosis of the hip: clinical and imaging features.

Transient osteoporosis of the hip is a form of reflex sympathetic dystrophy characterized by pain, limping, limitation of hip joint motion, and delayed radiographic patchy osteoporosis of the proximal femur. Spontaneous resolution is usually paralleled by radiographic recovery, usually within a few months. We present clinical and imaging features in seven cases of unilateral transient osteoporosis of the hip. In the appropriate clinical setting, conventional radiography will support the diagnosis. The role of more sensitive imaging techniques such as bone scintigraphy and magnetic resonance imaging in the early diagnosis of this disease has yet to be defined.


Mastectomy with immediate reconstruction: issues and answers.

Immediate breast reconstruction at the time of mastectomy, whether it involves prosthetic implantation or a myocutaneous flap procedure, has become a standard option for the care of breast cancer patients. The advantages of breast reconstruction are well understood: it helps to eliminate many of the psychological burdens with which mastectomy patients must contend and allows patients to participate in a normal lifestyle. Immediate breast reconstruction eases much of the initial psychological trauma of mastectomy. For patients who require postoperative radiation, reconstruction is often far less complex if done immediately than if delayed, even though radiation increases the chances of capsular contracture. The knowledge that immediate breast reconstruction is available may reduce patient's reluctance to seek medical advice when they find a breast lump.


Lipid and lipoprotein abnormalities in lower-extremity arteriosclerosis obliterans.

The prevalence of abnormal lipid and lipoprotein values was determined in 125 consecutive patients with lower-extremity arteriosclerosis obliterans, and the lipid and lipoprotein abnormalities in these patients were characterized. Only 13% of the patients had normal lipid/lipoprotein profiles. Forty-eight percent of patients had low levels of high-density lipoprotein cholesterol. High-density lipoprotein cholesterol values were lower in patients with concomitant coronary heart disease compared with those without heart disease. High-density lipoprotein cholesterol values were inversely related to weight, to triglyceride values, and to diabetes mellitus. Twenty-eight percent of patients had "desirable" total cholesterol levels (< 200 mg/dL), and 32% had low-density lipoprotein cholesterol values less than 130 mg/dL. Following National Cholesterol Education Program guidelines may be misleading in patients with documented lower-extremity atherosclerosis; therefore, complete lipid/lipoprotein profiles should be performed in these patients.


Uses of hyperbaric oxygen therapy in the 1990s.

Hyperbaric oxygen can produce a variety of effects in addition to reducing air and gas embolism. It increases the killing ability of leukocytes and is lethal to certain anaerobic bacteria. It inhibits toxin formation by certain anaerobes, increases the flexibility of red cells, reduces tissue edema, preserves intracellular adenosine triphosphate, maintains tissue oxygenation in the absence of hemoglobin. In addition, it stimulates fibroblast growth, increases collagen formation, promotes more rapid growth of capillaries, and terminates lipid peroxidation. These actions of hyperbaric oxygen are useful in treating anaerobic infections that result in gas gangrene, as well as severe aerobic infections such as necrotizing fasciitis, malignant external otitis, and chronic refractory osteomyelitis. Hyperbaric oxygen can help preserve ischemic tissues and facilitates the rapid spread and arborization of new capillaries. It promotes healing in certain problem wounds. Adjunctive hyperbaric oxygen treatment is a new approach to the management of radionecrosis. Hyperbaric oxygen treatment reduces morbidity and mortality resulting from carbon monoxide poisoning. Protocols for hyperbaric oxygen therapy are at present mostly empirical; much additional research is needed to better define therapeutic indications.


The role of citrate complexes in preventing urolithiasis.

There is considerable clinical evidence that the oral administration of potassium citrate significantly reduces the incidence of calcium oxalate stone formation in the urinary tract. The effectiveness of citrate ions in preventing stone formation could be due to the reduction in the concentrations of calcium and oxalate ions caused by complex ion formation with the citrate ions and/or due to the inhibition of the crystallisation of calcium oxalate. This paper reports an experimental study aimed at elucidating the role of citrate complexes in preventing urolithiasis. An experimental method is described which allows the identification of two hitherto unknown complexes CaOx cit3- and (Ca cit2)4-. The stability constants of these complexes have been determined, respectively, as log K = 4.54 +/- 0.08 and beta 2 cit = 5.15 +/- 0.14 (25 degrees C, I = 0.16). The inclusion of these complexes in ion-equilibrium calculations led to the conclusion that the effectiveness of the citrate ion in preventing calcium oxalate stone formation is due to its inhibition of agglomeration or growth of calcium oxalate crystals rather than any significant reduction in the degree of supersaturation of urine.


Immunochemiluminometric assays (ICMA) specific for growth hormone releasing hormone 1-44 NH2 and 1-40 OH.

We describe specific two-site immunochemiluminometric assays able to directly measure human growth hormone-releasing hormone 1-44 NH2 and 1-40 OH concentrations in unextracted plasma. A common N-terminal antibody was purified from polyclonal rabbit antisera to growth hormone-releasing hormone 1-44 NH2 on a growth hormone-releasing hormone 1-29 NH2 linked affinity column and labelled with chemiluminescent acridinium ester. C-terminal specific monoclonal antibodies to growth hormone-releasing hormone 1-44 NH2 and 1-40 OH were raised in Balb/C mice and used as solid phase antibodies. Assay of fasting specimens from normal individuals gave medians (and ranges) of 23 pg/ml (2-200) and 30 pg/ml (3-134) for growth hormone-releasing hormone 1-44 NH2 and 1-40 OH, respectively. Samples from a series of acromegalics showed that most have values in the normal range though median values were higher, 56 pg/ml for growth hormone-releasing hormone 1-44 NH2 (P < 0.001) and 52 pg/ml for 1-40 OH (P < 0.001). Using these assays it will be possible for the first time to directly study the physiology and pathophysiology of these two peptides.


Empyema necessitatis: review of the manifestations of thoracic actinomycosis.

Actinomycosis is a relatively uncommon infectious process involving the chest. A case of thoracic actinomycosis mimicking an inflammatory breast carcinoma in an elderly woman is presented with a review of the literature. The authors suggest that considering this disease in the differential diagnosis of indolent pulmonary parenchymal and pleural lesions is essential if appropriate diagnostic tests are to be obtained and proper therapy initiated, thus avoiding unnecessary invasive procedures.