Implementing clinical guidelines: a quality management approach to reminder systems. "Reminders" (timely notices about specific clinical events to physicians or patients) are useful strategies for implementing clinical guidelines. These systems can vary widely in content, design, and purpose. This variability makes it difficult to compare systems or predict a reminder's efficacy in a particular setting. In this article, the authors suggest that too much attention has been paid to proving the efficacy of reminder systems as a general strategy or a comprehensive solution. Rather, the usefulness and effectiveness of reminder systems will be better appreciated when quality management principles are applied to designing, implementing, and maintaining them. Physicians must participate in finding the best solutions for clinical process problems, and reminder systems--when implemented as the "best solution"--must be monitored and improved continually on an ongoing basis to continue to meet physicians' needs.


The use of continuous quality improvement methods in the development and dissemination of medical practice guidelines. The federal government is currently supporting the development and dissemination of clinical practice guidelines. Physicians fear that payers who promote guidelines are more interested in reducing variation to control their behavior and contain health care spending than in improving quality of care. There is also apprehension that guidelines will shift the responsibility for quality to parties external to the physician-patient relationship and the local professional community. Continuous quality improvement (CQI) methods provide an avenue for physician responsibility and participation in guideline development which can alleviate these concerns. This article describes the efforts of one health maintenance organization (HMO) to use CQI techniques to mobilize plan physicians to develop, disseminate, and implement practice guidelines in a manner that satisfies the needs of physicians, patients, and the HMO.


Using the analytic hierarchy process (AHP) to develop and disseminate guidelines. To be effective, practice guidelines must accommodate the unique circumstances of individual patients. This article describes how the analytic hierarchy process (AHP), a decision-making technique, could be used to create flexible guidelines by linking guideline developers and clinical decision makers as coworkers in a common decision-making process. The advantages of using this approach for guideline dissemination are discussed and compared with other methods for disseminating and implementing guidelines. The clinical feasibility of the AHP approach is also reviewed.


The case for intensive dissemination: adoption of practice guidelines in the coronary care unit. Medical practice guidelines are being embraced enthusiastically by subspecialty and government organizations, but although hundreds have been developed at great public and private expense, there are few examples of how they have improved the quality of care or reduced health care costs. This article reports documented experience in changing physician behavior after implementing medical practice guidelines in the coronary care unit without altering physician incentives or imposing the threat of sanctions. Guideline adoption did require significant attention to the implementation process, including endorsement of guidelines by local "opinion leaders," validation by local data, and an intensive and concurrent implementation strategy.


Implementing practice guidelines through a utilization management strategy: the potential and the challenges. Although there is currently much enthusiasm for practice guidelines, far more energy and resources have been expended on their development than on their implementation. A prospective interventional trial was performed using a previously validated explicit practice guideline (decision aid) to decrease the hospital length of stay for selected "low-risk" patients with chest pain. Utilization management (UM) coordinators (RNs) and physicians were chosen to implement the guideline since these resource people are available in most hospitals, allowing for generalization of the experience. With explicit review criteria used for 624 patients, it was found that when the guideline was applied by UM coordinators, it had a sensitivity of 0.85, a specificity of 0.90, a positive predictive value of 0.76, and a negative predictive value of 0.94. The attending physicians failed to override falsely classified low-risk patient recommendations 51% of the time. Implicit review judged that outcome might have theoretically been worsened in two of these patients. Follow-up at 30 days after admission, however, revealed no untoward sequelae in falsely categorized patients discharged according to the guideline. Utilization management appears to be a promising mechanism for guideline implementation that is available in most institutions. However, the accuracy with which UM coordinators implement guidelines should be assessed rigorously. Guidelines should be implemented in an environment of checks and balances in which physicians have the ultimate responsibility for their patients' care.


Presentation of drug prescribing guidelines and physician response. Most Medicaid Drug Use Review (DUR) Programs disseminate prescribing practice guidelines by providing written reviews to physicians about specific prescribing practices that do not follow established criteria and inviting their comment. This study reviewed physicians' written responses to explore relationships between DUR communications and the degree to which these communications affect awareness of prescribing issues, increase knowledge, change erroneous beliefs, and generate intentions to apply the information appropriately. The form, content, and effective tone for all responses received in 1990 regarding five different drug therapy issues (N = 240) was recorded. Response rates, comprehension, counterarguments, and prescribing intentions varied by drug therapy issue. Attention to the communication process could improve the dissemination of prescribing practice guidelines by DUR Programs.


The impact of status asthmaticus practice guidelines on patient outcome and physician behavior. This study assesses the effects of a status asthmaticus guideline on patient outcome and pediatrician behavior in a staff model health maintenance organization (HMO). The guidelines were drafted by an asthma specialist in the HMO and then discussed with key clinical personnel. A preprinted protocol order form was developed to help implement the guideline into clinical practice. The medical records of pediatric patients admitted to the hospital with status asthmaticus before (N = 67) and after (N = 59) guideline development and implementation were reviewed. This study demonstrates that locally developed, treatment-specific guidelines based on scientific evidence and combined with a staff consensus process and a user-friendly protocol form can influence physician behavior and patient outcome positively.


A cross-sectional study of the relationship between age and current health status for persons with spinal cord injuries. As life expectancies of persons with spinal cord injuries increase, this population is aging rapidly. This trend requires that increasing attention be given to the healthcare needs of older persons with spinal cord injury. Follow up data on 11,117 persons injured since 1973 were analyzed by current age at 15-year intervals. Mean time postinjury was 4.7 years. Several trends were observed when comparing persons currently in the 16-30 year age group with persons in the oldest age group (age 76+). The percentage of persons independent in selfcare decreased from 61.9% to 29.1%. Ventilator use increased from 1.7% to 4.3%. Nursing home residence increased from 1.4% to 22.2%. The percentage of persons rehospitalized during the most recent year increased from 26.5% to 33.7%. Age was an important predictor of health status, but time postinjury was less important, perhaps due to the study's short postinjury time frame. While few differences in health status were observed in individuals between 16 and 60 years of age, persons in the oldest two age groups demonstrated lower levels of health status than younger individuals.


Young spinal cord injured patients in nursing homes: rehospitalization issues and outcomes. Most spinal cord injured (SCI) patients are discharged to their homes and families after they complete their initial rehabilitation program. Nursing homes, however, were the discharge destinations for 3.9% of all SCI patients nationally. When a nursing home is the only discharge option for a young SCI adult, certain economic, medical and psychosocial incongruencies make this placement potentially stressful for both the nursing home staff and the young patient. This study of the rehospitalization of 12 SCI patients under the age of 50 who were discharged to nursing homes explores the issues of cost, care and outcome during their first year following nursing home admission. Nine of the 12 patients were rehospitalized a total of 21 times, mainly for urinary tract infections and decubiti. Charges for 18 of these 21 rehospitalizations amounted to over $423,110 for 599 days of care. Four of these 9 patients died before the end of the first year. Although this is a retrospective study of the medical records and follow up data for a small key group of SCI patients, it calls attention to the need for continued investigation into the outcomes of a minimally visible population that lacks advocacy for change.


New estimates of the direct costs of traumatic spinal cord injuries: results of a nationwide survey. New estimates of the direct costs of traumatic spinal cord injuries (SCI) are obtained from a comprehensive survey of the US SCI population. These direct costs, defined as the value (in 1988 dollars) of resources used specifically to treat or to adapt to the SCI condition, represent the average experience of the US SCI population. Responses to a detailed questionnaire administered to a sample of traumatic SCI persons in the United States provide the primary source of data for this study. Analysis of this survey data indicates that more recently injured SCI persons (ie those injured since 1970) spent an average of 171 days in a hospital over the first 2 years post injury. Initial hospital expenses will average $95,203. Home modification costs in excess of $8,000 can also be expected. After recovery and rehabilitation, a SCI person will pay, on average, $2,958 per year in hospital expenses and $4,908 per year for other medical services, supplies and adaptive equipment. Personal assistance costs and costs of institutional care will average $6,269 per year. These cost estimates represent the incremental costs of SCI, ie they exclude any costs that would have been incurred in the absence of SCI.


Correlation of bacteriological flora of the urethra, glans and perineum with organisms causing urinary tract infection in the spinal injured male patient. Positive urine cultures are common and often asymptomatic in the male spinal injured patient performing self clean intermittent catheterisation. It is possible that the positive urine cultures result from contamination from the colonised urethra at the time of catheterisation. This contamination could result in true infection of the bladder urine or yield false positive results, explaining the frequently seen asymptomatic cases. In a prospective study positive urine cultures were found on 58 occasions (74%) in 10 asymptomatic patients studied. In 19% of screenings, with positive urine cultures, an identical organism was cultured from the catheter specimen of urine, the perineum and the urethra. The flora of the anterior urethra is strongly correlated to that of the perineum (37.1%), as well as that of the bladder (52.6%). In 4 patients a correlation also existed between the urethra and fingers, and the perineum and fingers. This was associated with an increased incidence of positive urine culture in these patients. Suprapubic aspirates of urine before and after catheterisation cultured the same organisms. However, quantitative culture revealed colony counts that approached a 10-fold increase following catheterisation in one patient. This suggests that catheterisation is at least partially responsible for ascending infection in this group of patients. Catheter specimens were found to be a good representation of the bladder urine, with an 87.5% correlation.


N-nitrosamine generation by urinary tract infections in spine injured patients. Urine was collected from 33 patients resident at the Welsh Spinal Injuries Unit and analysed for volatile N-nitrosamines by gas chromatography. N-nitrosodime-thylamine, N-nitrosopiperidine or N-nitrosopyrrolidine was detected in 32 of the samples. Thirty-one of the samples were infected by one or more microbial species. Nitrate and N-nitrosamines were not found in the sterile urines of a group of 10 control individuals exposed to the same dietary and environmental influences as the spinal patients. Although N-nitrosamines were found in some of the catheter drainage system products, they did not elute into urine on 24-h exposure. In addition, 6 of the nitrosamine-containing urines had no contact with drainage systems as they were collected from spinal patients who were capable of independent voiding. It was concluded that the nitrosamines detected in the urines arose from the bacterial nitrosation of urinary amines. These results support the hypothesis that chronic urinary tract infection may have a role in the aetiology of bladder cancer in spine injured patients.


Event-related brain potentials during orienting to auditory and visual stimulation in spinal cord injured humans. In intact humans, deprivation of somatosensory and kinesthetic sensations result in significant alterations in perception and information processing. There have been very few studies to discover if the loss of sensation with spinal cord injury (SCI) in humans affects perceptual operations. We hypothesized that the SCI participant would either exhibit arousal, perceptual, and information processing alterations similar to experimentally sensory deprived subjects (who provide the closest human analogue), or that the somatosensory cortex would show reorganization for the processing of other modalities of stimulation. The subjects consisted of 16 paraplegic, 13 quadriplegic, and 22 non SCI controls. Subjects received an auditory orienting task consisting of a 500 Hz tone presented 20 times each at 66, 75, 88, and 101 db and a visual orienting task incorporating light flashes of 115, 123, 131, and 140 lux presented 20 times each. EEG information processing data were recorded from C3 and C4 for 100 msec prior to and 500 msec post stimulation. Information processing variables, analyzed as event-related potentials, indicated that the somatosensory cortex of SCI groups had a flattened response to auditory stimulation. The control group had a significantly larger P2 component. We concluded that these data signified that the somatosensory cortex did not reorganize function in response to chronic deafferentation nor was the SCI subject hyperresponsive to stimulation.


Enhanced carotid-cardiac baroreflex response and elimination of orthostatic hypotension 24 hours after acute exercise in paraplegics. To test the hypothesis that an acute bout of maximal exercise can ameliorate orthostatic hypotension consequent to prolonged wheelchair confinement, we evaluated heart rate (HR), systolic (SBP) and diastolic (DBP) blood pressure responses during 15 minutes of 70 degrees head-up tilt (HUT) in 10 paraplegic subjects 24 hours after arm crank exercise designed to elicit maximal effort, and during a control (no exercise) conditions. Additionally, the carotid baroreceptor stimulus-cardiac response relationship was determined by measurement of R-R interval during external application of graded pressures to the carotid sinuses. One week separated the treatment conditions. The maximum slope of the carotid-cardiac baroreflex response was increased (p = 0.049) by exercise (6.2 +/- 1.7 msec/mmHg) compared to control (3.3 +/- 0.6). During control HUT, HR increased from 61 +/- 1 to 90 +/- 7 bpm (p = 0.001) while SBP decreased from 118 +/- 5 to 106 +/- 9 mmHg (p = 0.025). During HUT 24 hours after exercise, HR increased from 60 +/- 2 to 90 +/- 4 bpm (p = 0.001), but the reduction in SBP was essentially eliminated (116 +/- 5 to 113 +/- 5 mmHg). The reduction in SBP during control HUT (-12.0 +/- 4.6 mmHg) was four-fold larger (p = 0.017) than during HUT following exercise (-3.1 +/- 3.9 mmHg). DBP during HUT was not altered in either condition. A single bout of intense, dynamic arm crank exercise eliminated orthostatic hypotension in paraplegics. Equal HR response with smaller reduction in SBP during HUT after exercise was consistent with a measured increased sensitivity of the carotid-cardiac baroreflex.(ABSTRACT TRUNCATED AT 250 WORDS)


An examination of dietary intakes and nutritional status of chronic healthy spinal cord injured individuals. To examine the nutritional composition of the dietary intake of chronic healthy spinal cord injured (SCI) individuals, 33 subjects affiliated with 3 SCI rehabilitation centers logged their food consumption for 7 days. Prior to record keeping, subjects were trained by a registered dietitian on the accurate recording of their standard food choices and portion size, and were provided with scales to weigh food accurately. Dietary macro and micronutrients were analyzed with a computer software package, with nutritional analysis compared to the recommended daily allowances (RDA) of the Food and Nutrition Board of the National Academy of Sciences. Analysis showed caloric intake to be 75% of that recommended for able bodies persons, with a high reliance on fat for calories. Fat intake accounted for 37.9% of calories, well above the recommended level of 30%, but typical of the American diet. The ratio of polyunsaturated to saturated fat was approximately one half the recommended level, with carbohydrate calories averaging 16.5% below optimal RDA. Protein consumption was within normal range, but average dietary fiber was only 25% of recommended levels. Micronutrient analysis showed deficiencies in both water and fat-soluble vitamins, with suboptimal intake of multiple minerals. Given the apparent reliance on a high-fat and low-carbohydrate diet, this research shows that nutritional intervention and education of SCI persons are needed, and that a registered dietitian should be included in the SCI health care team.


Pregnancy, labor and delivery post spinal cord injury. There are approximately 3,000 women of childbearing age who become spinal cord injured each year in the United States. There are few reports in the literature that address pregnancy, labor and delivery in this patient population. We are reporting on 22 women post spinal cord injury who had 33 pregnancies. There were equal numbers of paraplegic and quadriplegic women. Three pregnancies aborted, one spontaneously. The babies were near normal or normal weight with one exception. The mothers waited 5 years on average to become pregnant. Cesarean section was performed on 43% of pregnancies. Abnormal presentations occurred in over 10% of pregnancies. Indications for cesarean section included 5 that were repeats; the remainder were necessary due to bleeding (1), breech presentation (1), transverse presentation (2), lack of progress (2), onset of labor 1 day post spinal fusion, and a mother's request to have tubal ligation. Epidural anesthesia was selected for 9 deliveries; 6 of these patients had controlled autonomic hyperreflexia. Five general and 4 local anesthetics were used, and 12 patients received no anesthesia. Diagnostic ultrasound and amniocentesis were used selectively. Complications included autonomic hyperreflexia (9), frequent urinary tract infections, infected pressure sores (3, 2 resulting in below-knee amputations), seizures during and after delivery, pneumonia, bladder stones (2), episiotomy dehiscence (1), and breakdown of spinal fusion. The newborns were healthy, although one double footing breech vaginal delivery had an APGAR of 1 at 1 min, 7 at 5 min and 9 at 10 min. One premature baby, who weighed only 1600 g, was a precipitate birth at home unattended. Implications for the care of pregnant SCI women are discussed.


Oesophageal trauma in patients with spinal cord injury. Oesophageal perforations associated with cervical fractures occur from a variety of injuries. Fractures of the cervical spine, blunt trauma and penetrating injuries such as gunshot wounds, knives and missiles, perforate the cervical oesophagus. This retrospective study consists of 24 patients with an oesophageal perforation and cervical fracture. Motor vehicle accidents were responsible for 54% of the oesophageal perforations. The other oesophageal injuries were related to anterior spine surgery, gunshot wounds and sports-related activities. The clinical features related to these injuries included the obvious signs of an oesophageal perforation as well as fever of unknown origin, leukocytosis and unexplained persistent tachycardia. A variety of techniques was used to establish the diagnosis. All the patients had treatment for the cervical fracture and 20 patients required surgical repair of the oesophagus. The most common oesophageal complications were stricture of the oesophagus (54%) and oesophageal diverticulum (10%). The other complications were atelectasis, pneumonia, tracheobronchitis, pulmonary embolism, cervical osteomyelitis, cervical abscess, mediastinitis, septicemia and cervical fistulae. These patients have a serious life-threatening illness that may be difficult to diagnose and treat.


Morphometric evaluation of myofibrillar mitochondria in experimental administration of ethylene glycol. The authors carried out morphometric analysis of the surface, area, circumference and shape of myofibrillar mitochondria in rats submitted for acute experimental intoxication with ethylene glycol. The measurements were taken at 12 and 24 hours after intoxication and compared with those in the control group. A significant increase in mitochondrial circumference and surface area was seen as early as 12 hours with their shape being more rounded than elongated. At 24 hours of the experiment the parameters further increased. The use of computer image analysis permitted an objective and measurable confirmation of changes in electronograms and revealed the presence of disorders in the phase in which traditional methods were useless.


Ultrastructural signs of myocardial damage due to acute experimental intoxication with ethylene glycol. The authors carried out ultrastructural studies of the myocardial sections from inbred Wistar rats in the course of acute experimental poisoning with ethylene glycol. It was shown that slight mitochondrial swelling with clearing of the matrix, myofibrillar edema with decreased electron density of the sarcoplasma and widening of channels of the smooth intraplasmatic reticulum were visible as early as at 12 hours after intoxication with no changes in light microscopy. The changes were located mainly in the subendocardial layer of the ventricles and papillary muscles. At later stages of the experimental ultrastructural changes markedly progressed. Mitochondrial swelling enhanced with destruction of mitochondrial crests, myelin-like figures formed, myofibrillar necrosis and contraction bands developed and segmental or complete dissection of the intercalated disk edges appeared. The chages were scattered all over the myocardium predominating in the subendocardial layer and papillary muscles.


Relation between cardiovascular pathologic conditions and malignant tumours as seen by pathologist. I. Frequency of malignant neoplasms in the population with myocardial hypertrophy as seen by pathologist. Relatively low co-existence of malignant neoplasms and chronic cardiovascular disease was documented in this work the emphasis being put on the conditions running with myocardial hypertrophy. The percentage of malignancy in the total autopsy material of 5821 men and 6849 women was 27.8 and 23.0 resp., and in the subgroup with heart weight 300-400 g, 36.8 and 31.0 resp. This percentage was significantly lower in separated subgroups of: a. arterial hypertension, 6.6 and 10.2, b. cardio-pulmonary syndrome, 23.0 and 18.5, c. healed myocardial infarct accompanied by myocardial hypertrophy, 13.3 and 11.7, d. acquired valvar deformity, 15.3 and 10.1. The subgroup of heart weight 150-250 g showed 57.2% and 46.6% of cases with malignancy while that of cardiac weight over 600 g-7.4% and 5.7%. In the subgroup of normal right-(2-3 mm) and left-ventricular (10-12 mm) wall thickness corresponding percentage equalled 29.4 and 30.1, in the subgroup of right-ventricular wall thickness over 6 mm--14.4 and 8.8, and in that of left-ventricular wall thickness over 18 mm--12.5 and 9.4. Scanty available information suggests some antimitotic activity of catecholamines believed to condition that of chalones. Catecholamines are also attributed with the stimulation of myocardial hypertrophy. The correlation of our findings with assumptions mentioned above seem to justify a hypothesis, or only a possibility, that compensatory mechanisms active in the cardiovascular diseases create an unfavourable background for the development of neoplasm.


Fibrinoidal leucodystrophy (Alexander's disease) at 13 months girl. A case report. The case of Alexander's fibrinoidal leucodystrophy that was presented below is an exemplar of extremely rare degenerative disease of the CNS. On the grounds of the clinical course of the disease it seems that our case can be reckoned as an early childhood form of Alexander's disease. An interesting difference that pays attention is the marked hydrocephalus. In the most cases of Alexander's disease the volume of ventricular system is normal however most of authors expresses that it sometimes can be slightly and insignificantly enlarged.


Molecular genetics of neuronal ceroid lipofuscinoses. This overview describes recent advances in molecular biology of neuronal ceroid lipofuscinoses (CLN). Despite intensive research during last 20 years, the basic defects of these autosomal recessive-progressive encephalopathies of childhood remain unknown. Consequently, no specific cure is available. Methods of positional cloning (reverse genetics) starting from random linkage approach have been applied to search for gene defects in the infantile and juvenile forms of the disease. The results of this random search for disease loci have for the first time revealed molecular heterogeneity of CLN diseases. The gene defect causing the infantile form has been assigned to 1p32 in the Finnish family material, whereas the disease locus of the juvenile form has been localized to 16p12 in European and Canadian families. Finally, the gene defect causing the late infantile form has been excluded from both 1p32 and 16p12 chromosomal regions, referring to a third, still unknown locus causing CLN disease. Consequently, reliable prenatal and carrier diagnostics have now become possible in families with the infantile and juvenile forms of the disease, and DNA-based prenatal diagnostics have been successfully applied in the infantile form. Most importantly, the assignment of gene loci has brought these fatal brain diseases within the reach of molecular cloning strategies that eventually will result in revealing both the infantile and juvenile CLN genes and in identifying corresponding gene products.


Differential developmental expression of the rat kininogen genes. The rat liver expresses two low molecular weight kininogens (T-KG and K-KG). Although they share 90% of the nucleotide sequence in their 5' flanking regions, T- and K-KG genes are differentially regulated. The T-KG gene is inducible, and its protein is a potent thiol-protease inhibitor. In contrast, K-KG gene is expressed constitutively and encodes the precursor of the vasoactive nonapeptide bradykinin. To further elucidate the differential regulation of T- and K-KG genes, we examined their developmental expression in the Sprague-Dawley rat. Northern blots of total liver RNA were probed with oligonucleotides complementary to T and K-KG mRNA under high-stringency conditions. A single T-KG mRNA (1.8 kb) and two K-KG mRNA species (1.6 and 2.3 kb) were consistently detected at all ages studied. Steady state T-KG mRNA levels increased 3.5-fold at birth and remained high during the 1st week of postnatal life only to decline thereafter. T-KG immunoreactivity in the liver and plasma determined by Western blot analysis paralleled T-KG mRNA expression. In marked contrast, K-KG mRNA expression was not altered during the transition from fetal to neonatal life, nor was it affected by postnatal maturation. The results demonstrate that the fetal rat liver synthesizes kininogens and that T- and K-KG genes are differentially regulated during development. Up-regulation of T-KG synthesis after birth may serve a protective function in the newborn via its antiprotease activity.(ABSTRACT TRUNCATED AT 250 WORDS)


Developmental cellular electrophysiologic effects of propafenone on the rabbit atrioventricular node. Transmembrane recordings and surface electrograms were used to evaluate the influence of propafenone on the cellular electrophysiology of isolated neonatal and adult rabbit atrioventricular node (AVN) preparations. An automatic interval of 863 +/- 82 ms (mean +/- SEM, n = 14) in neonates was found to be significantly shorter than the 1510- +/- 205-ms (n = 12) automatic interval observed in adults. Propafenone in a concentration of 5 x 10(-6) M significantly increased the automatic interval of neonatal pacemakers but not that of the adult preparations. These changes in automaticity produced by propafenone were not dependent on the adrenergic receptor-blocking action of the drug. The pacemaker escape time after overdrive pacing was also shorter in the neonate than in the adult. Propafenone prolonged the escape time of the neonatal tissues but not those of the adult. AVN refractory period, A-H interval, and antegrade Wenckebach rate were comparably increased in a concentration-dependent manner in both age groups. The maximum diastolic potential was decreased by propafenone in the neonatal atrionodal tissue but not in other regions of the AVN and not in any region of the adult AVN. Action-potential duration was increased in all regions of the AVN in both age groups. Action-potential amplitude and maximum upstroke velocity were decreased by propafenone in both age groups. Unlike other excitable tissues of the heart, the action-potential duration of AVN nodal cells increased with decreasing pacing intervals as the pacing interval approached the Wenckebach interval.(ABSTRACT TRUNCATED AT 250 WORDS)


In situ morphology of the foramen ovale in the fetal and neonatal rat. In situ cross-sectional morphology of the foramen ovale was studied after rapid whole-body freezing of the fetal and neonatal rat. In the fetus, the foramen ovale was open widely toward the left atrium with a thin, short primum septum. The opening area of the foramen ovale was 40% of the cross-section of the thoracic inferior vena cava, and the ratio of the long diameter to the short diameter was 2 to 1. After birth, the primum septum became longer, thicker, and straighter, with less leftward bowing. The opening of the foramen ovale diminished in the first 2 d and closed completely 3 d after birth. Postnatal thickening of the primum septum was very remarkable, increasing by 400% in the first 2d, while only minimal change was noticed in the right and the left atrial walls. The length of the primum septum was short and was only 90% of the diameter of the fossa ovalis in the fetus. It increased and reached 97% and 111% of the diameter of the fossa ovalis 1 and 2 d after birth, respectively. The septum secundum also grew rapidly after birth, and its length and width increased by 40% and 29% after 1 and 2 d, respectively. These observations indicate a sudden, explosive growth of the atrial septum in the early neonatal period in the rat.


Plasma thyroid hormones and prolactin in premature infants and their mothers after prenatal treatment with thyrotropin-releasing hormone. We assayed TSH, triiodothyronine, free thyroxine, and prolactin (PRL) in plasma of women and infants participating in a trial of prenatal thyrotropin-releasing hormone (TRH) treatment for prevention of newborn lung disease. Women in labor at 26-34 wk of gestation received 400 micrograms of TRH i.v. every 8 h (one to four doses) plus 12 mg betamethasone (one or two doses); controls received saline plus betamethasone. Mean cord concentrations in control infants were TSH 9.7 mU/L, triiodothyronine 0.6 nmol/L (40.2 ng/dL), free thyroxine 14.4 pmol/L (1.13 ng/dL), and PRL 67.6 micrograms/L. TRH increased maternal plasma TSH by 100% at 2-4 h after treatment and decreased levels by 28-34% at 5-36 h. In cord blood of treated infants delivered at 2-6 h, TSH, triiodothyronine, and PRL were all increased about 2-fold versus control, and free thyroxine was increased 19%; the response was similar after one, two, three, or four doses of TRH. In treated infants delivered at 13-36 h, cord TSH and triiodothyronine levels were decreased 62 and 54%, respectively, and all thyroid hormones were lower after birth at 2 h of age versus control. We conclude that prenatal TRH administration increases thyroid hormones and PRL in preterm fetuses to levels similar to those normally occurring at term. Pituitary-thyroid function is transiently suppressed after treatment to a greater extent in fetus than mother, and infants born during the early phase of suppression do not have the normal postnatal surge in thyroid hormones.


Alae nasi activation in preterm infants during oral feeding. Preterm infants may demonstrate impaired ventilation during oral feeding with resultant hypoxemia and hypercarbia. This study was designed to determine whether infants activate a representative upper airway muscle, the ala nasi, in response to these ventilatory changes. Ten preterm infants (postconceptional age at study 35 +/- 4 wk, weight 2.2 +/- 0.1 kg) were studied during a control period, continuous feeding, subsequent intermittent feeding, and a period of nonnutritive sucking. Nasal airflow was measured with a pneumotachometer to quantify minute ventilation. The alae nasi electromyogram (EMGAN) was recorded with surface electrodes, and sucking pressure was detected by a catheter in the feeding nipple. End-tidal CO2 and O2 saturation were also recorded during each period. The percentage of breaths associated with EMGAN activity increased from 41 +/- 13% during the control period to 95 +/- 5% and 93 +/- 7% during continuous and intermittent sucking, respectively (p < 0.05). Eighty-seven +/- 5% of EMGAN activity occurred during inspiration. During continuous and intermittent sucking, the amplitude of EMGAN activity also increased (6.8 +/- 5.2 and 6.7 +/- 4.0 arbitrary units/breath, respectively) compared with the control period (2.4 +/- 2.8 units/breath, p < 0.05). In association with the increase in EMGAN activity, O2 saturation fell from 98 +/- 1% in the control period to 95 +/- 1% during both continuous and intermittent feeding (p < 0.05), and minute ventilation fell from 274 +/- 80 mL/min/kg during the control period to 190 +/- 81 and 208 +/- 57 mL/min/kg during continuous and intermittent feeding, respectively (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)


Docosahexaenoic acid status of term infants fed breast milk or infant formula containing soy oil or corn oil. The objective of this study was to compare circulating lipid docosahexaenoic acid [22:6(n-3), DHA] levels in term infants fed a powdered (CORN oil) or liquid (SOY oil) infant formula or human milk (HM). Infants whose mothers chose not to breast feed were randomly assigned to the CORN or SOY formula group. The formula fat differed in linolenic acid [18:3(n-3)] content: it was 0.8% for the CORN and 4.8% for the SOY. Linoleic acid [18:2(n-6)] was 31.5 and 34.2% fatty acids in the CORN and SOY formula, respectively. The formulas or HM were fed from birth through 8 wk of age, and growth and the plasma and red blood cell (RBC) phospholipid fatty acid composition was determined at 3 d, 4 wk, and 8 wk of age. Growth did not differ among groups. The plasma phospholipid and RBC phosphatidylethanolamine DHA was similar in the CORN and SOY formula groups at all ages. Plasma and RBC phosphatidylethanolamine levels of DHA were significantly lower in infants fed the CORN or SOY formula than in infants fed HM during wk 4 and 8. Plasma and RBC 22:5(n-6) was not increased in the formula groups at any age. The formula content of linolenic acid had no effect on the RBC or plasma DHA levels of the infants. The biologic or functional significance of the lower plasma and RBC DHA in infants fed formula rather than HM is unknown. The need for a dietary source of DHA and specificity of plasma or RBC phospholipid DHA as a measure of desaturation and elongation of linolenic acid in developing organs remains uncertain.


Effects of a protein-rich diet during convalescence from shigellosis on catch-up growth, serum proteins, and insulin-like growth factor-I. Shigellosis in children can cause growth retardation, worsening of malnutrition, and hypoproteinemia. To assess the effects of ingestion of a protein-rich diet during convalescence, 22 children aged 2 to 4 y with culture-proven shigellosis were randomly assigned after 5 d of antibiotic treatment to 21-d feeding regimens of either a 150 kcal/kg/d high-protein diet with 15% of calories as protein or an isocaloric control diet with 6% of calories as protein. At the start and end of dietary treatment, weight, height, mid-arm circumference, skinfold thickness, serum protein concentrations, and serum IGF-I were measured. Means of weight gain and increases in mid-arm circumference were greater in children fed high-protein diets than those fed control diets (1.23 versus 0.76 kg; 1.40 versus 0.96 cm; p < 0.05). Mean increase in height in children fed high-protein diets (0.83 cm) was not significantly greater than with control diets (0.74 cm). Mean increases in serum concentrations of total protein, prealbumin, and retinol-binding protein were greater in the high-protein group than in controls (p < 0.05). Mean serum concentrations of IGF-I were low in both groups before treatment [4.2 +/- 2.6 nmol/L (31.9 +/- 19.6 ng/mL) in controls; 3.1 +/- 3.4 nmol/L (24.0 +/- 26.3 ng/mL) in the high-protein group] but increased more in the high-protein group [39.0 +/- 16.2 nmol/L (298 +/- 124 ng/mL)] than in the control group [16.7 +/- 9.2 nmol/L (128 +/- 70 ng/mL), p < 0.01].(ABSTRACT TRUNCATED AT 250 WORDS)


Energy expenditure, lipolysis, and glucose production in preterm infants treated with theophylline. Theophylline is administered to preterm infants with pulmonary disease to improve pulmonary function and reduce apneic episodes. Because it potentially mediates both alpha- and beta-receptor-effector mechanisms, we tested the hypothesis that it increases lipolysis, gluconeogenesis from glycerol, and energy expenditure in 16 preterm infants, eight of whom were treated therapeutically with theophylline for apnea of prematurity (T) and eight of whom were controls (C). Mean +/- SD postnatal ages were 4.8 +/- 1.9 wk (T) and 2.4 +/- 0.9 wk (C) (p < 0.01). Corrected gestational ages were 35 +/- 1.6 wk (T) and 34 +/- 0.5 wk (C) (p = NS). Body weights were 1.69 +/- 0.13 kg (T) and 1.70 +/- 0.23 kg (C) (p = NS). All infants were clinically stable, breathing room air, fed enterally, and receiving no diuretics, steroids, or antibiotics. Lipolysis, hepatic glucose production, and gluconeogenesis from glycerol were measured using [2-13C]glycerol and [6,6-3H2] glucose tracers. Body water and energy expenditure were measured by the 2H2(18)O method. Body water volumes were 68.5 +/- 3.4% body weight (T) and 70.2 +/- 3.4% (C) (p = NS), suggesting fat was 10-13% of body weight in both groups. Mean daily energy expenditure was 65 +/- 22 kcal/kg body weight/d (T) versus 59 +/- 5 kcal/kg body weight/d (C) (p = NS). Between 4 and 6 h after a feeding, glucose production rates were 40.5 +/- 4.3 mumol/kg/min (T) and 37.6 +/- 4.8 mumol/kg/min (C) (p = NS).(ABSTRACT TRUNCATED AT 250 WORDS)


Effects of an early weaning on phosphate transport maturation in the rat kidney: influence of the phosphate content of the diet. The renal phosphate (Pi) transport system matures during the 3rd postnatal wk in the rat by an increase in the carrier affinity for sodium-cotransported phosphate. This study examines the ability of pups to adapt their renal Pi transport to the dietary phosphorus content during this period of carrier affinity maturation, corresponding to the weaning period in the rat. Clearance experiments and brush border membrane studies were performed on 21-d-old rats weaned early on d 16 onto a low phosphate diet (LPD, 0.19 g/100 g), a normal phosphate diet (control, 0.78 g/100 g), or a high phosphate diet (HPD, 1.5 g/100 g). In LPD rats, the Pi fractional excretion (0.3 +/- 0.1%) was lower than in controls (18 +/- 3%, p < 0.001). It remained very low (0.21 +/- 0.05% in LPD rats versus 40.5 +/- 6.3% in controls, p < 0.001) after Pi perfusion (1.5 mumol.min-1.100 g-1) and the reabsorbed Pi per min, corrected for the glomerular filtration rate, was higher than in the two other groups. The calcium fractional excretion (12.6 +/- 1.02%) in the LPD rats was much higher than in the controls (0.42 +/- 0.2%, p < 0.001). In contrast, HPD rats had an elevated Pi fractional excretion (41 +/- 4%, p < 0.001), whereas reabsorbed phosphate per min corrected for the glomerular filtration rate was not increased by a Pi load.(ABSTRACT TRUNCATED AT 250 WORDS)


Glycogenesis in the cultured fetal and adult rat hepatocyte is differently regulated by medium glucose. We examined the glycogenic response to glucose in cultured fetal and adult rat hepatocytes. After a 48-h culture in Dulbecco's modified Eagle's medium, 1 mM glucose, insulin, and cortisol, cells were cultured for 4 h in serum-free medium containing glucose (1-30 mM) and U-14C-glucose. Incorporation of 14C-glucose into glycogen was greater in fetal hepatocytes compared with adult hepatocytes at all glucose concentrations (p < 0.001). Net glycogenic rate in fetal cells was greatest between 1 and 8.3 mM (7.7- +/- 1.1-fold increase) compared with a 3.8- +/- 0.6-fold increase in adult cells. In contrast, there was a 19.4- +/- 2.7-fold increase in glycogen accumulated between 8.3 and 30 mM glucose in the adult and a 1.6 +/- 0.1-fold increase in the fetus. Total glycogen synthetase activity was higher in fetal than adult hepatocytes (p < 0.001), but the active a form was similar in fetal and adult hepatocytes. Glycogen synthase a/+b was stimulated at 8.3 mM or greater glucose in fetal hepatocytes, and 5.7 mM or greater in adult hepatocytes (p < 0.05). Total phosphorylase did not change with medium glucose, but glycogen phosphorylase a/a4+b decreased in adult hepatocytes incubated in 5.7 mM glucose or greater (p < 0.05). Fetal phosphorylase a/a+b was increased at 8.3 mM or greater glucose (p < 0.05). In contrast, both adult and fetal phosphorylase were activated by glycogen. A glucose-induced increase in active phosphorylase may induce the decrease in net glycogenic rate at high glucose in fetal hepatocytes.(ABSTRACT TRUNCATED AT 250 WORDS)


Mitochondrial ATP-synthase deficiency in a child with 3-methylglutaconic aciduria. We report the finding of mitochondrial ATP-synthase deficiency in a child with persistent 3-methylglutaconic aciduria. The child presented in the neonatal period with severe lactic acidosis, which was controlled by Na-HCO3 and glucose infusions. During the 1st y of life, there were several episodes of lactic acidosis precipitated by infections or prolonged intervals between meals. The excretion of lactate in urine was variable, but there was a persistent high excretion of 3-methylglutaconic acid. The activity of 3-methylglutaconyl-CoA hydratase in fibroblasts was normal. The child had a hypertrophic cardiomyopathy and magnetic resonance images revealed hypoplasia of corpus callosum. The gross motor and mental development was retarded, but there were no other neurologic signs. Investigation of muscle mitochondrial function at 1 y of age revealed a severe mitochondrial ATP-synthase deficiency (oligomycin-sensitive, dinitrophenol-stimulated Mg2+ ATPase activity: 27 nmol x min-1 x (mg protein)-1, control range 223-673 nmol x min-1 x (mg protein)-1. The mitochondrial respiratory rate was low and tightly coupled. The respiratory rate was normalized by the addition of an uncoupler. Low Mg2+ ATPase activity was also demonstrated by histochemical methods. Morphologic examination revealed ultrastructural abnormalities of mitochondria. There was no deletion of mitochondrial DNA. The sequences of the ATP synthase subunit genes of mitochondrial DNA were in accordance with published normal sequences.


A study of perceptual development for musical tuning. Musical tuning perception in infancy and adulthood was explored in three experiments. In Experiment 1, Western adults were tested in detection of randomly located mistunings in a melody based on musical interval patterns from native and nonnative musical scales. Subjects performed better in a Western major scale context than in either a Western augmented or a Javanese pelog scale context. Because the major scale is used frequently in Western music and, therefore, is more perceptually familiar than either the augmented scale or the pelog scale are, the adults' pattern of performance is suggestive of musical acculturation. Experiments 2 and 3 were designed to explore the onset of culturally specific perceptual reorganization for music in the age period that has been found to be important in linguistically specific perceptual reorganization for speech. In Experiment 2, 1-year-olds had a pattern of performance similar to that of the adults, but 6-month-olds could not detect mistunings reliably better than chance. In Experiment 3, another group of 6-month-olds was tested, and a larger degree of mistuning was used so that floor effects might be avoided. These 6-month-olds performed better in the major and augmented scale contexts than in the pelog context, without a reliable performance difference between the major and augmented contexts. Comparison of the results obtained with 6-month-olds and 1-year-olds suggests that culturally specific perceptual reorganization for musical tuning begins to affect perception between these ages, but the 6-month-olds' pattern of results considered alone is not as clear. The 6-month-olds' better performance on the major and augmented interval patterns than on the pelog interval pattern is potentially attributable to either the 6-month-olds' lesser perceptual acculturation than that of the 1-year-olds or perhaps to an innate predisposition for processing of music based on a single fundamental interval, in this case the semitone.


Prime time: fatigue and set effects in the perception of reversible figures. Subjects viewed unambiguous versions of both stationary and rotating Necker cube illusions for varying durations prior to the presentation of the standard ambiguous figure. In each case, the subjects were more likely to report the ambiguous figure to be (1) in the same configuration as that of the preceding prime following brief preexposure periods and (2) in the opposite configuration from that of the preceding prime following long preexposure periods. In addition, the number of reversals of the figure during the test period was also strongly related to the duration of the preexposure period, with progressively fewer reversals reported following longer preexposure periods. The results are interpreted as revealing the concurrent roles of "set" effects in the brief preexposure conditions and neural fatigue effects in the long preexposure conditions. Furthermore, the ability of the proposed two-process model to integrate the myriad of empirical effects in the reversible-figure literature is emphasized.


Eigenvectors of the inertia tensor and perceiving the orientation of a hand-held object by dynamic touch. Subjects wielded an object, hidden from view, and reported the orientation in which the object was positioned in the hand. The object consisted of a stem with two branches forming a V attached perpendicularly to the stem's distal end. The branches were differentially weighted so that the same spatial orientation of the object was associated with different orientations of its principal (symmetry) axes or eigenvectors. Perceived orientation was found to be dependent on the eigenvectors of the object's inertia tensor, computed about the point of rotation in the wrist, rather than on its spatial orientation. The results underscore the significance of the inertia tensor to understanding the perception of spatial properties by dynamic touch.


Haptic perception of object distance in a single-strand vibratory web. Can humans, like other animals, perceive distance by mechanical vibrations transmitted in a solid medium? In seven experiments, subjects perceived the distances from the hand of occluded metal disks attached to a taut nylon strand. Mechanical waves were initiated at the hand by the subject or at the disk by the experimenter. The results of Experiments 1 and 2 showed that perceived distance was linearly dependent on object distance with or without practice. The results of Experiments 3 and 4 revealed an inverse dependency of perceived distance on strand tension. In Experiment 5, a constant difference in perceived distance between vertical and horizontal strand manipulations was found. The results of Experiments 6 and 7 showed that distance was perceptible when the mechanical wave was not initiated by the subject. The informational basis for this haptic spatial ability was sought in the dynamics expressed by the one-dimensional wave equation, specifically, in the constants relating strand forces to strand motions.


Binocular unmasking with unequal interocular contrast: the case for multiple Cyclopean eyes. Under certain conditions, the detection threshold for a sinusoidal grating embedded in a noisy background may be an order of magnitude lower when binocular cues are available than when monocular cues only are present. Such binocular unmasking occurs only when the degree of interocular disparity for the target differs from that of the background. Two classes of models have been advanced to account for such unmasking. The first assumes that orientation-specific, spatial frequency channels in each eye encode the amplitude and phase of the spatial frequency component of the pattern the channel is tuned to detect. Thus, a difference in interocular disparity between target and background could result in interocular amplitude and/or phase differences in left- and right-eye spatial frequency channels. When, however, there are no disparity differences between target and background, there will be no interocular differences in amplitude and phase in the left- and right-eye channels. In this model, then, binocular unmasking reflects the binocular system's ability to respond to interocular amplitude and/or phase differences in the patterns presented to the two eyes. In the second class of models, it is assumed that the left- and right-eye patterns are first summed to form a "Cyclopean" eye. In these models, detection depends on the effect this summation process has on the power spectrum of the summated patterns. To decide between these two classes of models, we observed the occurrence of binocular unmasking when (1) the contrast of masker and signal was varied identically in both eyes and (2) the contrast of masker and signal was varied in one eye only. Consistent with our previous research, we found that the results can be accounted for in terms of a linear summation model of binocular unmasking; the alternative interocular phase detection model was disproved. The implications of these findings for binocular contrast summation in the absence of visual noise are discussed.


Stages of manual exploration in haptic object identification. In a yes/no identification task using touch alone, subjects indicated whether an object belonged to a named category. Previously, we found that subjects explored in two stages--first grasping and lifting the object, then executing further exploratory procedures (Lederman & Klatzky, 1990b). We proposed that Stage 1 (grasp/lift) was sufficient to extract coarse information about multiple object properties, whereas Stage 2 was directed toward precise information about particularly diagnostic properties. In the current study, subjects were initially constrained to grasping and lifting, after which they could explore further. Accuracy was above chance after Stage 1, confirming our assumption that the grasp/lift combination was broadly useful. Stage 2 increased accuracy and confidence. It primarily elicited exploratory procedures associated with object geometry, but exploration was also influenced by diagnostic object properties.


The perception of shrinking in apparent motion. Apparent motion was produced using two triangular patterns of different sizes, each exposed for 100 msec, with a 50-msec interstimulus interval and 200-msec recycle interval. The triangles were aligned either on center or on the midpoints of the bases. In Experiment 1, filled, outline, and three-dot triangles were viewed over four backgrounds: a blank illuminated field, and texture gradients constructed from horizontal lines, perspective lines, or a combination of these (full texture). In Experiment 2, outline and dot triangles were presented in one of three orientations: base down, base right, and base up over a blank background. Subjects made two forced-choice responses: apparent size was categorized as shrinking or not shrinking, and apparent motion was categorized as motion in depth or motion in a fixed frontal plane. The type of alignment was the major determiner of responses. When the midpoints of the base were aligned, the predominant response described a shrinking object in a fixed position in depth. When the centers were aligned, the predominant response described an object of constant size moving in depth.


The perceived strength of illusory contours. Illusory contours are not well understood, partially because a lack of physical substance complicates their specification via physical standards. One solution is to gauge illusory contours with respect to luminance-defined contours, which are easily quantified physically. Accordingly, we chose a metric (perceived contrast) that expresses illusory contour strength in terms of the physical contrast of luminance-defined contours. Using this metric, adult observers adjusted the contrast of a luminance-defined contour until it matched the perceived contrast of an illusory contour. Illusory contour length, inducer size, and inducer contrast all influenced illusory contour strength. The results are adequately explained via low-level visual processes. It appears that matching paradigms can be beneficial in quantitative studies of illusory contours.


Psychophysical features of the transition from pure heat perception to heat pain perception. The psychophysical features of the transition from the pure heat to the heat pain range were studied in 25 healthy subjects (mean age 28.8 years). Thirty short heat stimuli from -1.6 degrees C to +1.6 degrees C relative to the pain threshold were applied to the thenar of the left hand with an apparatus containing a Peltier thermode (nine different temperatures at 0.4 degrees C intervals). The subjects rated the sensation intensity on a visual analogue scale. The resulting stimulus/sensation intensity relations could be explained equally well (same goodness of fit) by a model with a power function (PF) and by a model with two linear regression lines (TLR), one for stimulus intensities below and one for those above the pain threshold and intersecting at the pain threshold. The slopes of the TLR model were significantly larger above the pain threshold than below it. The PF model produced exponents between 1.8 and 1.9. We conclude that to describe the transition area, it is sufficient to use simple linear models for both the pure heat and the heat pain ranges.


Cooperative tapping: time control under different feedback conditions. The same isochronous tone sequence was presented simultaneously to two mutually isolated subjects. In half the trials, accentuation in this sequence was accomplished by doubling the duration of the first and then of every fourth tone; in the other half, by doubling the frequency of those tones. The subjects' task was to follow the rhythm of the resulting four-tone patterns by finger tapping to tone onsets. There were four auditory feedback (FB) conditions: (1) no FB; (2) FB from the subject's own motor responses; (3) "alien" FB from the motor responses of the other pair member who, in turn, was listening to FB from his/her own tapping; (4) mutually "crossed" FB, where each pair member listened to FB from the tapping of the other. Tap onsets regularly preceded stimulus onsets. The observed order of the amount of this anticipation (from least to greatest) was: (1) own FB, (2) no FB, (3) alien FB, and (4) crossed FB. No mutual dynamic influence between simultaneously performing subjects was detected. Anticipation was more pronounced for sequences that were accentuated by frequency rather than by duration changes. The type of accent also influenced timing of intertap intervals in the rhythmic patterns. For the frequency accent, regular timing was produced, whereas for the durational accent, shortening of the second and lengthening of the fourth (the last) intertap interval were observed. The presence and source of feedback as well as the character of accentuation are therefore relevant factors in the timing of auditorally controlled rhythmic motor behavior.


The interaction of perceived distance with the perceived direction of visual motion during movements of the eyes and the head. A horizontally moving target was followed by rotation of the eyes alone or by a lateral movement of the head. These movements resulted in the retinal displacement of a vertically moving target from its perceived path, the amplitude of which was determined by the phase and amplitude of the object motion and of the eye or head movements. In two experiments, we tested the prediction from our model of spatial motion (Swanston, Wade, & Day, 1987) that perceived distance interacts with compensation for head movements, but not with compensation for eye movements with respect to a stationary head. In both experiments, when the vertically moving target was seen at a distance different from its physical distance, its perceived path was displaced relative to that seen when there was no error in perceived distance, or when it was pursued by eye movements alone. In a third experiment, simultaneous measurements of eye and head position during lateral head movements showed that errors in fixation were not sufficient to require modification of the retinal paths determined by the geometry of the observation conditions in Experiments 1 and 2.


Marginal leakage of impregnated Class 2 composites in primary molars: an in vivo study. In vivo impregnation of the cervical margin was used in an attempt to prevent leakage of class 2 composite restorations in primary molars. Examination after 18 months demonstrated clinical success of the restorations. However, the exfoliated teeth presented extensive dye penetration at the approximal margins of the restorations, suggesting that impregnation did not prevent marginal leakage.


The retention of amalgam and composite resin by a smooth, reverse-tapered pin. In this study, the retention of composite resin and amalgam by a smooth, reverse-tapered pin was compared to that of threaded pins. The smooth pin was significantly lower in retention than the threaded pins for each material, and caused a greater frequency of failure of the restorative material than the threaded pins. The newer smooth pin is probably not an improvement over the conventional threaded design.


Surface roughness of polished amalgams.

Surface roughness of polished amalgams. The purpose of this project was to determine the amalgam surface roughness following finishing and polishing procedures. Nine high-copper amalgams were tested. They were hand-condensed in a 3 x 3 x 30 mm mold. Each sample was divided into four sections, and each section was finished by one of four methods: carving only; carving and then burnishing 15 minutes after carving; carving and then polishing at the prescribed times; or carving, burnishing 15 minutes after carving, and then polishing at the prescribed times. Each bar of amalgam had these surface treatments done at either 1, 3, 6, or 24 hours. The results indicated surface roughness may be more dependent on particle size, shape, and distribution of the individual high-copper amalgams than the polishing time or the surface treatment performed.


The effect of retention grooves on posterior composite resin restorations: an in vitro microleakage study. An in vitro study was undertaken to evaluate the effect of retention grooves on the gingival marginal seal of class 2 posterior composite resin restorations when filled by the bulk and incremental techniques. Class 2 cavities were prepared in 40 extracted molar teeth. Retention grooves were prepared at the axioproximal line angles in 20 teeth. The teeth were then filled with Herculite posterior composite resin using the bulk and incremental techniques. Microleakage was assessed by radioisotope (I125) diffusion at the gingival margin, quantitatively by radiation counting on an I125 Gamma Counter and qualitatively by autoradiographs. Those class 2 cavities that were prepared with retention grooves and filled in layers showed the least radioisotope diffusion (a mean radiation count of 1588.5), while bulk insertion of the composite resin in cavities without retention grooves showed the most microleakage (mean count of 6092.4).


Effect of air/water rinse versus water only and of five rinse times on resin-to-etched-enamel shear bond strength. This study compared the shear bond strength of composite resin bonded to etched, flattened enamel that had been rinsed for 0, 1, 2, 3, 5 or 20 seconds with either a water stream or an air/water spray. One hundred seventy-six molars were separated into mandibular and maxillary groups, then divided equally into 11 groups of 16 teeth each. The facial enamel surfaces were ground flat and etched for 20 seconds with 37% phosphoric acid gel. In one group, the etching gel was dried but not rinsed. In five groups the gel was rinsed with a direct stream of water at 22 psi. In the remaining five groups the gel was rinsed with an air/water spray (air at 53 psi, water at 22 psi). One tooth from each group was removed for scanning electron microscopy evaluation, leaving 15 specimens in each group for shear bond testing. Teflon tape with a 3 mm in diameter window was placed over each etched area, a light-curing liquid resin was applied and polymerized for 10 seconds, and a cylinder of light-curing composite resin was polymerized over the window. Specimens were thermocycled from 5 to 50 degrees C for 500 cycles (30-second dwell time). After 30 days' hydration at room temperature, the teeth were mounted and the composite resin cylinders were loaded in shear to failure with an Instron machine at a cross-head speed of 5 mm/min. Mean load to failure was calculated for each group. Specimens that were not rinsed had significantly (P < 0.001) less bond strength (mean 0.53 MPa) than any of the rinsed specimens (mean 18.7 MPa).(ABSTRACT TRUNCATED AT 250 WORDS)


The influence of antidepressants on aggressive behavior in stressed rats: the role of dopamine. The influence of dopamine (DA) receptor blockers (haloperidol, sulpiride) on electric footshock-induced fighting behavior and on the effect of antidepressants (imipramine, clomipramine, nomifensine, mianserine) was investigated in chronically stressed male Wistar rats. Exploratory activity in an open field was measured in the same groups of animals. The effect of chronic stress and antidepressants on DA utilization in the brain was also investigated. It was shown that 48 h after the last session of repeated stress (various unpredictable stressors over 16 days) the number of fighting attacks was significantly reduced. However in stressed rats treated chronically (for 14 days) with antidepressants the intensity of fighting was restored to control value. On the contrary, when the stressed rats, receiving antidepressants chronically, were pretreated with DA receptor blockers: haloperidol (0.5 mg/kg) or sulpiride (50 mg/kg) but also alpha 1-adrenergic receptor blocker - prazosin (3 mg/kg) the effect of antidepressants was abolished. Exploratory activity was not significantly reduced under influence of stress. Neither antidepressants nor sulpiride modified exploratory activity of stressed rats. Haloperidol and prazosin but not sulpiride decreased this activity of normal, stressed and antidepressant-treated rats. It is concluded that prolonged treatment with antidepressants counteracts the decrease in aggression induced by chronic stress and that DA mechanism participate in this effect of antidepressant drugs.


The responsiveness of D1- and D2-dopamine receptors in the striatum and hypothalamus of spontaneous and vasopressin hypertensive rats. Low doses of apomorphine (20-50 micrograms/kg) induced an increase in the activity of an endogenous inhibitor of cAMP dependent protein Kinases (type I inhibitor) in the striatum, anterior and posterior hypothalamus of normotensive rats by stimulating D2-dopamine receptors. In contrast, high doses of the compound (2-10 mg/kg) produced a dose dependent decrease in type I inhibitor activity. In the posterior hypothalamus of vasopressin hypertensive rats and SHR the maximal increase of type I inhibitor activity was markedly higher than in normotensive animals. Moreover, apomorphine induced the increase of type I inhibitor activity in a much wider range of doses. Only as high dose of the compound as 10 mg/kg was able to decrease type I inhibitor activity. This points to a marked supersensitivity of D2 receptors and suggests the subsensitivity of D1 receptors in this brain area of hypertensive rats. In contrast, in the striatum and anterior hypothalamus of hypertensive rats the apomorphine dose response curves were similar to those in normotensive rats. Thus, it seems tha hypertension is associated with the alteration in sensitivity of D2 and D1 receptors in the posterior hypothalamus, the brain area involved in regulation of blood pressure.


Effect of captopril on serotonergic mechanisms in two-kidney, one-clip renal hypertensive rats. In 2K,1C-RHR (two-kidney, one-clip hypertensive rats) serotonergic mechanisms in blood platelets were studied. The endogenous serotonin (5-HT) concentration in whole blood and in platelets remained unchanged in relation to the sham operated rats. Also the uptake of labelled 5-HT in rats with renal hypertension was not altered. However platelets aggregability was increased in 2K,1C-RHR. Acute administration of captopril (10 mg/kg and 100 mg/kg po) diminished blood pressure but did not change either the concentration of 5-HT in whole blood and in platelets of hypertensive rats or the uptake of this amine. Platelets aggregation and the amplifying effect of 5-HT in hypertensive rats were also unchanged after acute captopril administration. Similar results were observed after its administration in a dose of 30 mg/kg for one week. Our results indicate that captopril did not affect the platelets serotonergic mechanisms in 2K,1C-RHR.


Adenosine receptors in basolateral membranes of rat renal cortex. High affinity binding sites for adenosine were identified in rat kidney cortex basolateral membranes. Kinetic analysis indicates two sets of [3H]adenosine, [3H]ADO, binding sites, one with high affinity and Kd = 0.84 +/- 0.25 microM, one with low affinity and Kd = 4.74 +/- 0.37 microM. The ADO receptors were further characterized using ADO analogs as binding inhibitors. The most potent inhibitor of [3H]ADO binding was N-methyl-adenosine with a Kd of 5 microM, whereas 2-deoxyadenosine was about 50 times less potent. The binding of [3H]phenylisopropyladenosine, [3H]PIA, and [3H]-N-ethylcarboxamidoadenosine, [3H]NECA, to basolateral membranes was rapid and reversible. The Scatchard plot of [3H]PIA binding showed monophasic curves for experiments performed at 0 degrees C and 37 degrees C. The apparent Kd of [3H]PIA binding at 0 degrees C was 0.19 +/- 0.05 nM and 0.34 +/- 0.07 nM at 37 degrees C. The binding of [3H]NECA to basolateral membranes was found with an apparent affinity Kd of 110 +/- 50 nM at 0 degrees C. Pretreatment of membranes with N-ethylmaleimide (NEM) inhibited the [3H]PIA binding and did not affect the [3H]NECA binding. These results demonstrate that both A1 and A2 adenosine receptors are present in basolatertal membranes of rat kidney.


The cusp of Carabelli in Malaysians.

The cusp of Carabelli in Malaysians. The maxillary casts of 320 Malaysian children were examined for the occurrence of the Carabelli trait on the maxillary first permanent molars. The total trait frequency was observed to be 52.2 per cent. Statistical analysis showed no sex dimorphism in the occurrence of the trait. Bilateral occurrence with a tendency towards concordance of expression between sides was also observed.


Use of subtherapeutical dose of cisplatin and vitamin C against murine Dalton's lymphoma. The antitumor activity of subtherapeutical dose of cisplatin and vitamin C combinations was studied against murine Dalton's lymphoma in vivo. The sequence-dependent synergistic antitumor effect of vitamin C and cisplatin was shown to lead to the regression of the tumor resulting in a significant increase in the host survivals with tumor free hosts. Decrease in tumor pH noted in the treated tumor bearing mice and involvement of host's immune system could be an important step in this sequence-dependent antitumor activity of vitamin C and cisplatin.


Double teeth--fusion or gemination?

Double teeth--fusion or gemination? Double teeth or joined teeth have been described under several different terms and the terminology is often confusing. There are several ways in which union of teeth can occur and the terms that are commonly used to describe the condition are fusion and gemination. Although primary double teeth themselves may be regarded as harmless anomalies, its presence can cause some abnormalities to occur in the permanent dentition. Therefore, early diagnosis of the anomaly is of considerable importance.


Synthesis and pharmacological properties of 2,4-disubstituted 5-amino-6-pyrimidinecarboxylic acid derivatives. Part II. 2,4-Disubstituted 5-amino-6-pyrimidinecarboxylic acid derivatives 5-20 were synthesized and evaluated for their pharmacological activity. Compounds 11-14, 17-19 showed antiaggressive effect, compounds 5, 8, 9, 11, 12 and 19 displayed antiserotonin activity while compound 14 exerted antireserpine action.


Cross-cultural variations in dental knowledge among antenatal mothers. This study evaluates the level of dental knowledge among 328 antenatal mothers from different ethnic groups and ascertains the importance of the various sources of dental information. The mothers were interviewed based on a structured questionnaire. Most mothers knew about the number of sets of teeth they possessed throughout their life. This was most evident among the Chinese and least among the Malays. Only 42.7% of the mothers interviewed were positive about the preservation of their teeth throughout life. This belief was highest among the Chinese followed by the Indians. However about 40% of the Chinese believed that tooth decay is hereditary. Generally the principal sources of dental information cited by most mothers were television or radio followed by dentists, school and family. This order of importance was similarly observed among the Malays and Chinese. However, among Indians, family members represent the second most important source of dental information. The implications of these findings are discussed.


Synthesis and local anesthetic and circulatory actions of aminoesters and hydroxyamine monoterpene derivatives. Esters of N,N-diethylaminoacetic acid and hydroxyamines, obtained from structurally different natural monoterpenes, were pharmacologically examined. It was proved that salts of the obtained compounds had local anesthetic properties in infiltration anesthesia, compounds 9, 6 and 8 having been more potent than lidocaine. Compounds 7-9 slightly increased the arrhythmogenic dose, and compound 12 - the lethal dose of strophanthin. All the examined compounds transiently decreased the arterial blood pressure and displayed a cardiopressive activity.


Understanding prevention of dental caries and gum disease in the singapore population. Prevention has been recognized as a cost-effective method for the control of oral diseases. Knowledge of prevention can influence preventive dental behavior. This study surveyed knowledge on the prevention of dental caries and gum disease among a selected group of adults. Respondents were asked to indicate the importance of numerous preventive measures for prevention of both categories of oral diseases. Results showed that while respondents appropriately identified the importance of regular brushing for prevention, the role of flossing is underestimated. Similarly, there was a lack of appreciation for the value of various fluoride treatment modalities in preventing dental caries. A lack of understanding of dental sealants was also evident. It is concluded that public knowledge on prevention of dental caries and gum disease deviates greatly from current scientific information.


An epidemiologic study of 70 oral cancer cases at the Institute of Dental Medicine, Yangon, Myanmar, 1985-1988. This study shows that in Myanmar, South-East Asia, the prevalence of oral cancers is a serious fact as they rank fifth among all cancers being known there. On the 70 oral cancer cases reported at the Institute of Dental Medicine, Yangon, the findings stressed that most patients, male or female, came from the metropolitan division (Yangon), had smoking and chewing habits. Also most of these patients came to hospital only at the severe and late stage. It confirms us in our opinion that early diagnosis and prompt treatment are a necessity.


Dens evaginatus in the Vietnamese.

Dens evaginatus in the Vietnamese. Dens evaginatus (supernumerary cusps in premolars) were detected in 50 of 4677 Vietnamese patients examined. A systematic study including morphologic, histologic, pathologic aspects of dens evaginatus was carried out and data were compared with those given in previous reports pertaining to dens evaginatus in other Asian countries. It is expected that a better knowledge concerning this anomaly will lead to appropriate measures for prophylactic treatment of dens evaginatus.


Cefaclor AF: correlation of microbiology and clinical outcome. Cefaclor is active against Haemophilus influenzae and Moraxella catarrhalis in addition to the pathogens typically susceptible to first-generation cephalosporins. Cefaclor advanced formulation (cefaclor AF) provides the opportunity for once or twice daily dosing of this agent. Clinical trials using cefaclor AF have been carried out in a number of centres on bacterial infections of the respiratory tract, the urinary tract and the skin. In vitro susceptibility tests on selected pathogens from the clinical trials were carried out according to National Committee for Clinical Laboratory Standards recommendations, generally with excellent agreement between in vitro and in vivo response.


Changes in the spectrum of organisms causing respiratory tract infections: a review. Over the last decade, the spectrum of organisms causing community-acquired acute lower respiratory tract infections has changed. Streptococcus pneumoniae now causes approximately 30% of outpatient acute pneumonia-less than in former decades-whereas Mycoplasma pneumoniae is found in both young and elderly patients. The Enterobacteriaceae and Staphylococcus aureus are now seen more frequently as respiratory tract pathogens in community-acquired pneumonia patients, and they are the major organisms causing pneumonia in residents of homes for the elderly or nursing homes, and in immuno-compromised patients. Agents that were previously considered non-pathogenic for the respiratory tract include serotypes of Haemophilus influenzae other than type b, H. parainfluenzae and Moraxella (Branhamella) catarrhalis; these organisms affect mainly patients with underlying cardiopulmonary disease. Legionella species can cause sporadic as well as epidemic disease of the lower respiratory tract. Chlamydia pneumoniae is a newly recognized pathogen responsible for mild to severe upper and lower respiratory tract infections. In 60-80% of cases, hospital-acquired pneumonias are caused by Gram-negative bacilli and S. aureus. These organisms colonize the mucosal membranes of the upper respiratory tract and penetrate into the lower tract by aspiration or intubation.


A multicentre trial of cefaclor advanced formulation versus cefaclor in the treatment of acute bronchitis. Two prospective randomized, double-blind, parallel studies were carried out in Europe to compare cefaclor advanced formulation (cefaclor AF) with cefaclor in the treatment of acute bronchitis caused by susceptible pathogens. A total of 1,321 patients suffering from acute bronchitis confirmed by clinical data and a negative chest X-ray were randomized for treatment in the two multicentre trials. Three doses of cefaclor AF were tested: 375 mg twice daily and 500 mg twice daily were compared with cefaclor 250 mg three times daily; and cefaclor AF 750 mg twice daily was compared with cefaclor 500 mg three times daily. Duration of therapy was seven days. Assessments (complete history, physical examination, sputum specimens for culture and Gram's stain, plus clinical and laboratory evaluations of safety) were carried out within 24 hours before the first dose, during therapy, within 72 hours after therapy completion and, in the 375 mg and 500 mg dose groups, 1-2 weeks after the end of therapy. There were no significant differences between the total evaluable cefaclor AF population and the total evaluable cefaclor population with regard to favourable post-therapy responses. Most favourable clinical and bacteriological response rates in the 375 and 500 mg doses were 80% or above. In the higher dose group, there was a favourable post-therapy symptomatic response in 100% of evaluable patients, with favourable bacteriological responses in 93.3% patients receiving cefaclor AF and 96.8% receiving cefaclor (no significant difference). Only one serious drug-related adverse event was reported (anaphylactic reaction). Adverse events related to the digestive system were reported by 4.7% of the cefaclor AF-treated patients and 4.5% of the cefaclor-treated patients during the entire study period. Cefaclor AF, at all three dose levels studies, was seen to be as safe as cefaclor in the treatment of acute bronchitis caused by Streptococcus pneumoniae, Haemophilus influenzae and Moraxella (Branhamella) catarrhalis.


Pharmacokinetics of cefaclor AF: effects of age, antacids and H2-receptor antagonists. The pharmacokinetics and bioavailability of cefaclor advanced formulation (cefaclor AF) were investigated in two studies, one comparing healthy elderly and younger volunteers and the other assessing the effects of an antacid and H2-receptor antagonist on cefaclor AF bioavailability. The pharmacokinetics of a 750 mg dose of cefaclor AF were studied in 30 subjects ranging in age from 65 to 84 years and 10 control subjects 21-45 years of age. Compared with controls, elderly subjects exhibited higher plasma concentrations of cefaclor which were attributed to lower plasma clearance. There was a strong association between age and renal function, and the plasma clearance of cefaclor was highly dependent upon renal function. Thus, elderly patients with impaired renal function had a reduced ability to eliminate cefaclor. Due to a short elimination half-life and wide therapeutic index, dosage adjustments are not necessary in patients exhibiting moderate renal dysfunction. The 15 healthy men in the second trial were crossed over to receive five treatments, including cefaclor AF (500 mg) alone, cefaclor AF with or preceded by cimetidine, cefaclor AF followed by Maalox TC and cefaclor immediate release (500 mg) alone. Cefaclor AF and immediate release cefaclor had similar bioavailability, but plasma concentrations were maintained for a longer period of time when cefaclor AF was administered. Cimetidine did not alter the bioavailability of cefaclor AF but Maalox TC, coadministered with cefaclor AF, reduced the extent of absorption. This suggests that cefaclor AF bioavailability is influenced by the antacid Maalox TC but not by H2-receptor antagonist cimetidine.


Cefaclor AF versus cefaclor in acute exacerbations of chronic bronchitis. The effectiveness and safety of cefaclor advanced formula (AF) compared with cefaclor in the treatment of acute exacerbations of chronic bronchitis were evaluated in multicentre trials in the United States and Europe. In the US study, patients were randomized to receive either cefaclor AF 375 mg twice daily or 500 mg twice daily or 250 mg cefaclor three times daily. Three dose levels of cefaclor AF were used in the European study: 375 mg, 500 mg and 750 mg twice daily; the comparative agent was cefaclor 250 mg three times daily in the 375 mg and 500 mg strata, and cefaclor 500 mg three times daily in the 750 mg stratum. The total number of patients receiving cefaclor AF was 667 versus 357 patients receiving cefaclor. Results showed that cefaclor AF administered twice daily at 375, 500 or 750 mg was as effective as cefaclor 250 mg three times daily for the treatment of acute exacerbations of chronic bronchitis. Evaluable patients receiving cefaclor AF in the US study had a clinical response rate of over 90% and a bacteriological response rate of over 85%. In the European study, patients receiving cefaclor AF had clinical response rates over 85% and bacteriological response rates ranging from 50% to 85%. The safety profile for cefaclor AF was similar to that reported for other beta-lactam antibiotics.


Possible mechanisms of action of antimicrobial agent-associated gastrointestinal symptoms. Gastrointestinal symptoms, particularly diarrhoea, are a relatively common side effect of antibiotic usage. In the vast majority of cases the mechanisms involved in these side effects are not understood. Proposed mechanisms include the direct action of antibiotics on intestinal function, inducing predisposition to infection with an enteric pathogen, and factors secondary to disturbance of the normal intestinal flora that do not involve infection with a known pathogen. There is some evidence for all three potential scenarios.


Cefaclor AF in the treatment of streptococcal pharyngitis/tonsillitis. Two double-blind, double-dummy, randomized multicentre studies compared the safety and efficacy of 10-day regimens of cefaclor advanced formulation (cefaclor AF) (375 mg twice daily) with cefaclor (250 mg three times daily) in the treatment of proven group A beta-haemolytic streptococcal pharyngitis/tonsillitis. Of the 1,138 patients enrolled, 764 (cefaclor AF:392; cefaclor: 372) were evaluated for efficacy. All patients enrolled in the studies (570 treated with cefaclor AF and 568 treated with cefaclor) were evaluated for safety. Clinical and bacteriological evaluations were performed on treatment days 4-6, and after completion of treatment within 3-5 days and 2-3 weeks. In evaluable patients, the post-therapy clinical success and bacteriological cure rates for cefaclor AF were 96.7% and 93.6%, respectively; the rates were 98.1% and 94.1% for cefaclor. Sixteen cefaclor AF-treated patients and 14 cefaclor-treated patients withdrew early from the trial because of adverse events. There were no significant differences between treatment groups in the overall number of adverse events reported. Diarrhoea was the most frequently reported adverse event (5.6%) in cefaclor AF-treated patients, and headache/migraine was the most frequently reported adverse event (5.6%) in the cefaclor-treated patients. Cefaclor AF (375 mg twice daily) is as effective and safe as cefaclor capsules (250 mg three times daily) in the treatment of streptococcal pharyngitis/tonsillitis.


Ascertaining how much compliance is enough with outpatient antibiotic regimens. Compliance with outpatient antibiotic regimens can now be measured by electronically monitoring the time history of dosing. This new approach reveals that many patients comply only partially with prescribed regimens in randomized, controlled, outpatient trials. Omitted or delayed doses and early cessation of dosing are commonly observed. Partial compliance converts a fixed-dose trial into a set of natural experiments in dose ranging, presenting a variety of patterns of dose timing that can be correlated with clinical outcomes for an estimate of minimum compliance needed for satisfactory outcome. Reliable measures indicate little difference in compliance between once- and twice-daily regimens, but considerably higher rates of omitted doses with three-times-daily or four-times-daily dosing. A key practical issue is to ensure continuity of drug action in the face of the most common compliance errors. Continuity of action is more likely when the prescribed interval between doses is considerably shorter, preferably half or less, than the drug's duration of action, allowing doses occasionally to be delayed or omitted without a gap in drug action. Thus, a twice-daily regimen may be expected to maintain crucial continuity of drug action better than a once-daily regimen, even if a few more doses are missed. Errors to avoid in compliance with outpatient antibiotic regimens are prolonged intervals between doses and early cessation of treatment.


Comparative trials of cefaclor AF in uncomplicated cystitis and asymptomatic bacteriuria. Two different doses of cefaclor advanced formulation (AF), a new sustained-release formulation of cefaclor, were compared with the regular formulation of cefaclor for efficacy and safety in the treatment of uncomplicated cystitis and asymptomatic bacteriuria. A 7-day course of treatment was used, and the trials were double-dummy and double-blind. In one trial, cefaclor AF 500 mg once daily (at night) was compared with cefaclor 250 mg three times a day. Satisfactory clinical and bacteriological responses were found in 179/189 (94.7%) and 160/191 (83.8%) patients, respectively, given cefaclor AF and in 82/87 (94.3%) and 74/90 (82.2%) patients given cefaclor, 5-9 days after the end of treatment. In the other trial, cefaclor AF 375 mg twice daily was compared with cefaclor 250 mg three times a day. Satisfactory clinical and bacteriological responses were obtained in 164/180 (91.1%) and 156/184 (84.8%) patients, respectively, given cefaclor AF, and in 86/92 (93.5%) and 81/93 (87.1%) patients taking cefaclor, 5-9 days after the end of treatment. Very similar results were found in both studies in those patients who were assessable 3-5 weeks later. Only 4.3% and 2.4% of patients treated with cefaclor AF (375 mg and 500 mg, respectively) and 2.2% of cefaclor patients discontinued therapy due to adverse events. The three most commonly reported events were vaginal moniliasis or vaginitis (8.6%), headache (5.0%) and nausea (4.8%). No significant differences were found between clinical efficacy and safety parameters in the different study groups, and it was concluded that cefaclor AF in a twice-daily or once-daily dosage is as effective and as safe as the currently recommened three-times-a-day dosage of cefaclor.


Broad- versus narrow-spectrum antibiotic use: the role of in vitro testing and its correlation with clinical efficacy. The spectrum of activity of any antibiotic varies with time, the geographical locale and the site of isolation of the bacteria. This variability is related to the changing heterogeneity (specifically, the degree of resistance) of the bacterial population. In order to choose the most appropriate antimicrobial agent, it is necessary to know the infection site, the degree of diffusion of antibiotics at this site, and the pathogen responsible, and then to determine the sensitivity of the pathogen. If the pathogen is unknown, an assessment of the patient's clinical status should be made; generally, the weaker the patient, the broader the spectrum of antibiotics that should be used. If the pathogen and its in vitro susceptibility pattern are known, narrow-spectrum antibiotics are preferable. The carefully standardized conditions of in vitro testing do not correlate with the in vivo situation, in which the effectiveness of antibiotics is altered by diffusion and immune response. The in vitro tests available do not always correlate with the clinical situation; some bacteria showing resistance in the laboratory are actually susceptible in practice in some infection sites, and vice versa. In vitro tests are also affected by technical limitations. An in vitro test can aid the assessment of efficacy but cannot guarantee it.


Comprehensive safety profile of cefaclor AF in respiratory, urinary tract and skin infections. The safety of cefaclor advanced formulation (cefaclor AF) was evaluated in 3,272 patients participating in 11 controlled clinical trials in comparison with cefaclor (2,210 patients) for a variety of infectious illnesses. Daily doses of cefaclor AF ranged from 500 to 1500 mg, with a mean duration of treatment of 8.1 days (range 1-18 days). There were no significant differences between the cefaclor AF- and cefaclor-treated groups in the frequency of adverse events by body system for all events reported. The majority of adverse events related to therapy were mild and transient. Severe adverse events occurred in 2.1% of the cefaclor AF group and 2.7% of the cefaclor group. The most frequently reported adverse events for cefaclor AF were diarrhoea (3.4%), headache (3.2%), nausea (2.5%) and vaginal moniliasis (2.5% of females). Drug-related adverse events led to early discontinuations in 1.7% of cefaclor AF-treated patients and 1.6% of cefaclor-treated patients. Overall, there were few significant differences in the frequency of adverse reactions between older and younger patients. Notably, elderly patients reported significantly less diarrhoea and fewer hypersensitivity-type reactions. There were, however, more therapy discontinuations due to adverse effects in patients aged 65 years or older than in those less than 65 years of age. Many of the discontinuations were thought to be unrelated to therapy. Alterations in laboratory values in patients treated with cefaclor AF were similar to those seen with other beta-lactam antibiotics. The comprehensive data indicate that cefaclor AF is a safe therapeutic option for a variety of common bacterial infections.


Measurements of light transmission through single melanophores. A photometrical method has been developed that allows assessment of subcellular pigment migration in melanophores of the fish cockoo wrasse (Labrus ossifagus L.) The pigment migration was studied with local light spot transmission measurements. Depending on where the light beam is placed on the melanophores it is possible to study events within an area of approximately 75 microns 2. Measuring pigment translocation in different parts of a melanophore gives new possibilities to study how cell membrane receptor-mediated signals are spread within a single cell, which will increase our understanding of how receptor activating drugs exert their cellular effect. The technique can be used in pharmacological and biophysical studies and in biosensors, pharmaceutical screens, environmental detectors, etc. The method clearly has the ability to study local and small changes in light transmission due to displacement of melanophore pigment granules. Since one melanophore on the tip of an optical fibre would be enough to obtain a measurable effect, the presented technique provides the basis for future development of biosensors small enough for in vivo applications, e.g., to monitor the catecholamine levels of circulating blood.


Extracellular matrix constituents and pigment cell expression in primary cell culture. Three types of pigment cells were isolated and cultured from larval Rana pipiens, and their attachment, maintenance, and proliferation were examined in the presence of extracellular matrix constituents (ECMs) in primary cell culture. The initial profile of pigment cell types present on day 2 of culture reflects the relative attachment of the cells to the dishes. Changes in the numbers of cells present after day 2 reflects the influence of factors present in the culture media on the maintenance, proliferation, or detachment of each type of pigment cell. Fetal bovine serum (FBS) promoted melanophore expression, but inhibited iridophore expression. FBS had no effect on xanthophores. In contrast, ventral skin conditioned medium (VCM), which contains melanization inhibiting factor, strongly stimulated iridophore expression, while it markedly inhibited melanophore expression. VCM had little effect on xanthophores. Of the ECMs tested, collagen type I had no effect on pigment cells. Fibronectin slightly inhibited melanophore expression, while it moderately stimulated iridophores and xanthophores. The stimulatory effect of fibronectin was not as strong as that of FBS or VCM. Laminin was also tested; however, it did not allow pigment cells to attach to the dishes, at least under the culture conditions utilized. The results of these experiments are discussed in terms of the general mechanisms of pigment pattern formation.


Melanin standard method: titrimetric analysis. Melanin isolated from the ink sac of Sepia officinalis (Sepia melanin) has been proposed as a standard for natural eumelanin, and a standard mild isolation and purification protocol for Sepia melanin has been developed (Zeise, doctoral dissertation, Johns Hopkins University, 1991). The goal of the present work, developed using Sepia melanin, was to quantify the bioavailable carboxylic acid groups present in melanin particles. Bioavailability is governed by the accessibility of carboxy groups to the surrounding biological milieu, and is expressed as microequivalents of carboxy group per gram of melanin. The present work was carried out using an heterogeneous slurry of melanin in a nonaqueous system. A standard acidic titrant, and an automatic titrator operating in an equilibrium titration mode were used to characterize and quantify the carboxy group content of Sepia melanins and several other commonly used melanins purified by a standard method (Zeise et al., Pigment Cell Res. [Suppl] 2:48-53, 1992).


Melanin standard method: empirical formula 2. Natural melanins are composed of two distinct portions; a protein fraction and a chromophoric backbone. There is no unequivocal evidence for covalent bonding between these two fractions, and standard protocols used in protein purification have failed to separate the protein fraction from the chromophoric fraction. In order to study the chromophoric backbone, many workers have resorted to harsh isolation and purification protocols that are now known to degrade and damage the chromophoric portion. These artifactual melanin preparations are poor models for valid chemical, physical, and biological studies. We have developed a mild isolation and purification protocol for melanins that takes into consideration both the particulate nature of natural melanins and the stability characteristics of the chromophoric fraction. Mathematical factoring of the quantitative amino acid data into the elemental analysis was used to obtain the empirical formula of the chromophoric backbone of melanins. The analyses have shown that melanins from various sources have significantly different amino acid compositions and contents, molar C/N ratios, and empirical formulae. This method successfully differentiates melanins from a variety of sources, namely, human hair, Sepia officinalis, Sigma Chemical Company (cat. no. M8631), autoxidation of dopa, and from the feathers of Rhode Island Red chickens. Analytical results from these studies are presented and discussed.


Morphological and biochemical characterization of the cream markings in the integument of the female isopod, Armadillidium vulgare. Cream markings aligned along the dorsal region of the female isopod, A. vulgare, were investigated with light and a fluorescence microscope and an electron microscope. Biochemical studies were also carried out. The cream markings were observed in the dorsal integument as a group of cream-colored chromatophores that emit a yellow fluorescence. These chromatophores, which are distinguishable from ommochrome chromatophores, contained numerous granules in the cytoplasm, and these granules (0.6-3.0 micron in length by 0.4-1.5 microns in width) were electron-lucent and spheroidal in shape with a concentric arrangement of membranes. Based on various biochemical analyses, the principal component of the yellow pigment isolated from the cream markings was identified as sepiapterin. These facts revealed that the cream markings are the chromatophores that contain pteridine granules. The males have no cream markings like those of the females, since the cream-colored chromatophores are externally hidden by the ommochrome chromatophore layer. The content of sepiapterin in the males was about two times greater than that in the females. This quantitative difference in sepiapterin content between males and females suggests that the pteridine formation in this pigment cell may be regulated by hormones associated with sex determination.