Sex differences in signs and symptoms from masticatory and other muscles in 19-year-old individuals. Pain and tenderness of masticatory muscles are often related to muscle tenderness elsewhere in the body. It has been shown that women are more prone to musculoskeletal disorders than men. We sought to determine whether sex differences of muscular symptoms were established by the age of 19. The subjects comprised 51 boys and girls who received a questionnaire regarding the function of their masticatory system, frequency of headache, and neck, shoulder and low back pain. Their masticatory system was examined, and neck and shoulders were palpated. For all variables in the questionnaire girls reported symptoms more often than the boys. Of the subjects 50% had tender chewing muscles upon palpation. Again the girls had the most. There was good correlation between reports of pain in one area as compared to others. The number of clinically tender neck and shoulder muscles correlated with the number of tender masticatory muscles. It was concluded that girls presented more muscular symptoms than boys.


Complete mandibular denture stability when posterior teeth are placed over a basal tissue incline. Six patients with previous denture experience were provided with new dentures. Metal indicators were placed on either side of the mandibular denture and a cobalt-chromium alloy marker was inserted in the left bucco-posterior area of the mandible in each case. In the new dentures posterior teeth were positioned up to the retro-molar pad, over the basal tissue slope of the posterior mandibular alveolar ridge. After habituation had taken place, a cineradiographic recording was made of chewing. Prior to the second recording the mandibular teeth were removed to a point where the remaining teeth were not over inclined residual alveolar ridges. Denture movement was observed by measuring the distances between the markers on an analytical projector. The results show a significant difference between the cranial values of the two chewing experiences. Values for all denture movements were less after removal of the teeth over an incline. These results support the clinical observation that teeth placed over a basal tissue incline have a destabilizing effect during complete mandibular denture function.


Internal medicine training in ambulatory gynecology. To assess internists' perceptions of their training in the management of common problems in ambulatory gynecology and to compare these perceptions with their clinical practice experiences. We surveyed 325 internists in the Portland, Oregon, metropolitan area about their residency training and practice experiences in the diagnosis and management of 25 clinical problems in ambulatory gynecology and five nongynecologic problems. Responses were received from 159 internists (48.5%). Overall, the internists reported relatively little residency training in the management of many common gynecologic disorders. Women internists managed gynecologic problems more than did their male counterparts, independent of the number of women patients in their practices. Internal medicine residency programs need to expand training in ambulatory gynecology to better prepare graduates for clinical practice.


Discrimination of clenches at varied jaw positions using autoregressive model coefficients of myoelectrical activities of anterior temporal and masseter muscles. During 10% maximum clenching at intercuspal, protruded, retruded contact and lateral positions, the surface electromyograms (EMG) of bilateral anterior temporal and masseter muscles of 20 normal subjects with intact natural dentitions were recorded. The autoregressive (AR) model of the sampled EMG was then built and the obtained coefficients of the AR model were accepted as featured parameters of the EMG. Finally Bayes' stepwise discriminant analysis was used for establishing discriminant functions of estimating low level clenches at varied jaw positions. It was found that total conformation rates of internal and external sample substitution (15 and 5 subjects) were 82.67% and 78% respectively; the discriminant effect between intercuspal and retruded contact position was not up to predicted standard. The results indicate that AR model coefficients may describe the characteristics of surface EMG of masticatory muscles and easily be used in multiple statistical analysis, from which the classification and diagnosis may be taken.


Microleakage of indirect inlays placed on different kinds of glass ionomer cement linings. The objective of this study is to compare the marginal seal of Class II cavities restored with indirect inlays constructed on glass ionomer cement linings having different curing properties. Also the effect of acid-etching of these liners on microleakage was investigated. Mesio-occlusal and disto-occlusal cavities in 80 extracted human molars having the cervical floor below the cementoenamel junction were prepared (n:160). Half of the preparations were restored with Ceramco II porcelain and the rest with SR-Isosit resin inlay material. Liners as light curing Ionoseal light+chemically curing LCL 8 and Zionomer and chemically curing Ketac-Bond glass ionomer cements (GICs) were used. On mesial preparations GICs were acid-etched but were not on distal preparations. All inlays were cemented with Ultrabond composite material. After thermocycling the teeth were placed in a basic fuchsin dye solution for 24 h, then each tooth was sectioned. By using a stereomicroscope the extent of marginal leakage was scored and statistically evaluated. Microleakage was observed beneath all GIC linings and was more extensive between light curing GIC/dentine interface. By acid-etching of GICs the microleakage between GIC/dentine interface was increased significantly. Whether acid-etching was applied or not a significantly increased microleakage was recorded between chemically curing GIC/composite interfaces. Although the marginal microleakage was witnessed in both inlays, it appeared that porcelain inlays provided a better marginal seal, in comparison to SR-Isosit inlays.


Physics and the sounds produced by the temporomandibular joints. Part I. In clinical dentistry, the sounds (clicking) and noises (grating) produced by the temporomandibular joints (TMJ) usually signify dysfunction or disease of the mandibular locomotor system. In an attempt to provide guidance to the general practitioner, this article discusses some pertinent parameters defining the physics of airborne and solid-borne vibrations.


Maximum jaw opening capacity in adolescents in relation to general joint mobility. Mandibular jaw opening was related with general joint mobility in a non-patient adolescent group. The angular rotation of the mandible at maximum jaw opening was slightly larger in females than in males and significantly larger in hypermobile individuals. No significant relationship between linear measuring of maximal mandibular opening capacity and peripheral joint mobility was found either at active (AROM) or at passive range of mandibular opening (PROM). PROM was strongly correlated to the mandibular length. Clinical signs in the great jaw closer muscles could not be associated to decreased AROM. The mean value of the difference between PROM-AROM (DPA) was 1.2 mm. Frequent clenching and/or grinding was correlated to increased DPA only in hypermobile adolescents (r = 0.49***). Those with DPA exceeding 5mm had all reciprocal clicking.


Electromyographic parameters related to clenching level and jaw-jerk reflex in patients with a simple type of myogenous cranio-mandibular disorder. A discriminant analysis has been applied on several electromyographic (EMG) parameters of the masseter and the anterior temporal muscles, related to clenching and the jaw-jerk reflex, to characterize jaw muscle function of patients with craniomandibular disorder (CMD) with respect to controls. The subject samples, matched for age, consisted of 20 females with myogenous CMD, and 20 symptom-free females. The jaw-jerk reflex was elicited by a downward-directed mandibular load, transmitted by a bite-fork causing a similar occlusion and bite-rise as a splint. The patients differed mainly from the controls by smaller maximum EMG activity in both muscle groups (P less than 0.05 with the bite-fork inserted). This finding was related to a smaller muscle strength as the EMG level did not improve with pain-free jaw muscles after therapy using a relaxation splint. Discriminating factors of secondary importance were an enhanced bilateral asymmetry in the muscle activity of the patients, and in the reflex amplitude normalized for background EMG activity. In all subject samples, the activity of the anterior temporal muscles decreased with respect to the masseter muscles when the bite-fork was inserted (P less than 0.05-0.001). The therapeutic effect of a relaxation splint may, in part, be related to a relief of the temporal muscles.


An observational study of attending rounds. The authors conducted an observational study of attending rounds to determine the current status of this form of clinical teaching in a university-based internal medicine department. Using two forms of measurement, questionnaires and timed observations, we found that 63% of attending physician time was spent in the conference room, 26% in hallways, and only 11% at the bedside. Significant differences were found between estimated and actual times, particularly in discussing previously admitted patients, patient interactions, data reviews, topic presentations, and the category of "other" activities. These results provide a framework for appraising attending rounds and identifying areas that may be improved with a teaching workshop intervention.


Shrinkage of tissue conditioners with time--effect of the particle size in powder and the EtOH content in liquid. The dimensional change of tissue conditioners with time was measured until 4 weeks after mixing. Shrinkage of the materials was evaluated in relation to particle size in powder and the EtOH content in liquid. The dissolution of EtOH and plasticizer were also measured to investigate the relation to dimensional change. Shrinkage with time was recorded. The smaller the particle size in powder and the more EtOH in liquid, the greater the shrinkage rate. The smaller the particle size in the powder and the more EtOH contained in the liquid, the greater the dissolution of EtOH. The dissolution of BPBG was below 1/100 comparing that of EtOH and no difference was recognized by particle size and EtOH content. On the basis of these results it is suggested that the dissolution of EtOH is related to shrinkage of tissue conditioners with time and that the component particle size in the powder and EtOH content in the liquid have a significant influence on dissolution of EtOH associated with shrinkage.


Relationship between autoregressive model coefficients of EMG and its potentials of jaw closing muscles at rest position and clenching. At rest position and varied clenching levels at intercuspal position, autoregressive (AR) models of myoelectrical activities of both masseter and anterior temporal muscles of 11 healthy subjects with intact natural dentitions were established. The relationship between the AR model coefficients of surface EMGs and their potentials was analyzed by multiple linear regression. It was found that the fourth order coefficient of AR had the greatest effect on the EMG potential levels and their relationship was positive in all recorded muscles. The results indicate the AR coefficients may become a characteristic parameter to describe myoelectrical activity of jaw closing muscles.


Effect of mechanical pressure on the blood flow in human palatal mucosa measured by temperature controlled thermoelectrical method. Mucosal blood flow in the human palate was measured by a temperature controlled thermoelectrical method based on the thermal conductivity of mucosal tissue using a blood flow monitor and a non-invasive surface probe. The effect of mechanical pressure on the palatal mucosal tissue was studied. Mechanical pressure (2.5, 5.0, 7.5, 10.0 or 15.0 g mm-2) to the mucosal surface was exerted circumferentially around the surface probe. In five out of seven subjects, the blood flow showed a tendency to be almost constant under the mechanical pressures which are 10.0 g mm-2 or higher. The effect of the duration of the pressure (10.0 g mm-2) exertion on the blood flow was also investigated and it was revealed that the blood flow tended to be constant after 60s in every subject. In the present study, it was also demonstrated that the temperature controlled thermoelectrical method is appropriate for studying the blood flow dynamics in oral mucosa.


A new guide for positioning of maxillary posterior denture teeth. There is no definitive method for the arrangement of artificial teeth in complete denture construction. A new method is introduced whereby the maxillary posterior teeth have been set in approximate positions mediolaterally similar to their natural predecessors. The procedure is based on a constant relationship derived from the natural dentition. Its clinical application proved to be suitable for the arrangement of artificial teeth for complete dentures with minimal errors.


Observation of proportionality of myoelectrical activity of anterior temporalis to masseter muscle during clenching at varied jaw positions. Twelve healthy subjects with an intact permanent dentition and normal occlusion were selected for sampling of myoelectrical activity of their left and right anterior temporal and masseter muscles during habitual clenching level in varied positions. The proportionality of normalized myoelectrical potentials of anterior temporal muscle to masseter muscle at ICP and RCP was greater than one, while the proportionality at PP was less than one. In the lateral position, the proportionality on the working side was approximately equal to that at RCP, while the proportionality on the non-working side was similar to that at PP. These results suggest that temporal muscle contraction can bring the mandible upward and backward whilst the masseter muscle can elevate the mandible upward and forward.


Retinoblastoma and p53 gene expression related to relapse and survival in human breast cancer: an immunohistochemical study. Inactivation of tumour suppressor genes may be an important aetiological factor in many human cancers including breast. In a study of 197 breast cancer patients, tumour tissue was snap-frozen at the time of surgery and immunohistochemical labelling for p53 protein and retinoblastoma (Rb) gene product carried out using an indirect immunohistochemical technique. Tumours were scored by two independent observers for the intensity of nuclear staining for each antibody. Expression of p53 protein showed a significant association with a shorter time to relapse (P = 0.03) and death (P = 0.02) (log rank test). p53 expression did not correlate with nodal status but showed a significant association with high tumour grade (P = 0.001). Rb gene expression showed no relationship to relapse or survival but loss of expression showed a significant correlation with positive lymph node status. The manner by which these proteins might act to determine tumour behaviour remains to be established.


Inhibin (10.7 kD prostatic peptide) in normal, hyperplastic, and malignant human endometria: an immunohistochemical study. The expression of inhibin, a 10.7 kD follicle-stimulating hormone (FSH)-suppressing prostatic peptide of 94 amino acids, was investigated in normal human endometrium, endometrial hyperplasia, and adenocarcinoma, employing the avidin-biotin immunoperoxidase technique. The antiserum used was raised in rabbits against prostatic inhibin isolated from human seminal plasma. The study included 15 well differentiated, 32 moderately differentiated, and 21 poorly differentiated endometrial adenocarcinomas; 26 simple, five complex, and two complex atypical endometrial hyperplasias; and, for comparison, 25 normal proliferative and 30 normal secretory endometria. In malignant and hyperplastic endometrial tissues, inhibin was localized in the epithelial cytoplasm of endometrial glands while the stroma showed weak reactivity. On the other hand, inhibin was undetectable in the early proliferative phase, but was present on the luminal border of the glandular epithelium in the mid- and late proliferative phases. Secretory endometrium displayed strong inhibin reactivity in the cytoplasm of glandular epithelium and in the stroma. The increased inhibin reactivity in secretory endometrium as compared with the proliferative phase is indicative of a functional role for inhibin in the uterus. In addition, its localization in proliferative, hyperplastic, and malignant endometria suggests a possible regulatory role for inhibin in endometrial proliferation and growth.


Evaluation of PGP9.5 in the diagnosis of Hirschsprung's disease. The ability of an acetylcholinesterase-stained frozen section to detect an increase in large cholinergic nerve fibres within the muscularis mucosae and extending into the lamina propria was a significant step forward in the diagnosis of Hirschsprung's disease (HD). However, such frozen section diagnosis is not always possible. The purpose of this study was to assess the ability of PGP9.5 to detect this pattern of mucosal nerve fibre staining immunohistochemically. Sixty-four specimens were included in the study. Twenty-six of these had been diagnosed as HD by conventional means. All cases were stained immunohistochemically with PGP9.5, S100, and anti-neurofilaments (NF). Twenty-four cases of HD were also stained with neurone-specific enolase (NSE). PGP9.5 reliably stained fibres in the mucosal and submucosal plexuses, and ganglion cells, when the latter were present. This positive staining of ganglion cells was more intense than that seen with NSE, and the positive fibre staining was more intense than that seen with NF. Increased lamina propria fibres were detected with PGP9.5 in only 37 per cent of HD cases compared with S100 positive staining in 60 per cent of cases. However, when S100 staining was assessed alone, it gave a higher false-negative rate in diagnosing HD than PGP9.5 used alone. Therefore we would recommend the use of PGP9.5 and S100 together for the immunohistochemical diagnosis of HD in formalin-fixed biopsies.


The peritubular myofibroblasts in the testes from normal men and men with Klinefelter's syndrome. A quantitative, ultrastructural, and immunohistochemical study. The ultrastructure and immunostaining with antibodies against actin, desmin, and vimentin were studied in the peritubular myofibroblasts of testes from normal men and men with Klinefelter' syndrome (KS). The seminiferous tubules were classified into five types (a-e), related to the progressive degree of sclerosis measured as thickening of the lamina propria. In control testes, only types a and b tubules were present, whereas the testes from men with KS showed types b, c, d, and e tubules. The ultrastructural study revealed abundant microfilament bundles with electron-dense bodies in the cell periphery of the myofibroblasts in a and b tubules. In c tubules, the microfilament bundles of the myofibroblasts were lacking in electron-dense bodies. Myofibroblasts in tubules d and e showed scanty microfilament bundles. Immunostaining of peritubular myofibroblasts with anti-actin antibodies was intense in tubule types a-c and scanty in types d and e. Immunostaining of myofibroblasts with anti-desmin antibodies was intense in tubule types a and b, and negative in types c-e. Immunostaining with anti-vimentin antibodies was weak in tubule types a-c and intense in types d and e. Quantitative study revealed that with the progression of sclerosis, the number and volume per cross-sectioned tubule of actin-containing cells and, mainly, desmin-containing cells decrease while the number and volume of vimentin-containing cells increase.


Far-UV photochemistry and photosensitization of 2'-deoxycytidylyl-(3'-5')-thymidine: isolation and characterization of the main photoproducts. Far-UV irradiation of 2'-deoxycytidylyl-(3'-5')-thymidine (dCpT) gave rise to the pyrimidine (6-4) pyrimidone adduct and its Dewar valence isomer as the main photoproducts. The absolute configuration of the former adduct was determined and its photoisomerization studied. A comparison of the alkali lability of both compounds showed that hydrolysis of the phosphodiester bond occurs for the Dewar valence isomer but not for its (6-4) precursor. In addition, the trans-syn and cis-syn cyclobutane dimers of dCpT were obtained by acetophenone photosensitization and characterized. Finally, the deamination rate constants for this series of compounds were shown to be dramatically influenced by the nature and the configuration of the photoproducts.


Laser photolysis of cytosine, cytidine and dCMP in aqueous solution. Laser photolysis of cytosine and cytosine derivatives (cytidine and 2'-deoxycytidine-5'-monophosphate) using acetone as a sensitizer have been carried out in aqueous solution using a KrF laser. The absorption spectra of triplet states of cytosine and cytosine derivatives have been observed for the first time. From detailed kinetic analyses, the reaction mechanisms including triplet-triplet excitation transfer, and intramolecular excitation transfer within the exciplex arising from the interaction of triplet acetone with cytosine and cytosine derivatives, have been suggested. Accordingly, a series of kinetic parameters have also been obtained.


Photoinduction of albino-3 gene expression in Neurospora crassa conidia. The synthesis of carotenoids is induced by blue light in Neurospora crassa mycelia, while in conidia (the vegetative spores) the accumulation of carotenoids also occurs in the dark. The expression of the albino-3 (al-3) gene (coding for the carotenogenic enzyme geranyl-geranyl pyrophosphate synthetase) in isolated conidia was analysed. The level of al-3 mRNA was shown to be increased in light-induced wild type (wt) conidia. This light response was elicited by blue light and was under the control of the white collar-1 (wc-1) and white collar-2 (wc-2) gene products. This indicates that the blue-light photoreceptor and the light transduction pathway which activate al-3 gene expression in mycelia are probably the same as in conidia.


Effects of photodynamic therapy with topical application of 5-aminolevulinic acid on normal skin of hairless guinea pigs. Photodynamic therapy (PDT) is a relatively new approach to the treatment of neoplasms which involves the use of photoactivatable compounds to selectively destroy tumors. 5-Aminolevulinic acid (ALA) is an endogenous substance which is converted to protoporphyrin IX (PpIX) in the synthetic pathway to heme. PpIX is a very effective photosensitizer. The goal of this study was to evaluate the effect of PDT using topical ALA on normal guinea pig (g.p.) skin and g.p. skin in which the stratum corneum was removed by being tape-stripped (TS). Evaluation consisted of gross examination, PpIX fluorescence detection, reflectance spectroscopy, and histology. There was no effect from the application of light or ALA alone. Normal non-TS g.p. skin treated with ALA and light was unaffected unless high light and ALA doses were used. Skin from which the stratum corneum was removed was highly sensitive to treatment with ALA and light: 24 h after treatment, the epidermis showed full thickness necrosis, followed by complete repair within 7 d. Time-dependent fluorescence excitation and emission spectra were determined to characterize the chromophore and to demonstrate a build-up of the porphyrin in the skin. These data support the view that PDT with topical ALA is a promising approach for the treatment of epidermal cutaneous disorders.


Microbiological validation of a new manufacturing complex for an injectable biological product. The Raritan Biological Production Facility (RBPF) at Ortho Pharmaceutical Corporation, Raritan, NJ, is a unique facility designed and built exclusively for the production of a sterile, injectable biological product of murine monoclonal origin. This product is the first injectable monoclonal antibody product to be licensed by FDA's Center for Biologics-Evaluation and Research (CBER). Thus, Ortho's Biotechnology Division had a unique opportunity to work very closely with CBER throughout all aspects of facility design, construction and validation, including microbiological validation of the facility and its equipment. This paper will address how existing guidelines for pharmaceutical and sterile products were used to develop initial validation protocols for the different areas and applications within the facility, and how the data gathered were used, with the assistance of CBER, to develop operating specifications and monitoring programs, for the operations within the complex.


The Water Pressure Integrity Test--a new integrity test for hydrophobic membrane filters. Sterilizing grade hydrophobic filters are used for the sterile filtration of gases in pharmaceutical and biological applications. Until now the integrity of these membrane filters and their ability to retain bacteria, has been correlated to a solvent based nondestructive integrity test. Current methods use solvents to wet the membranes in order to perform bubble point and diffusion integrity tests. Solvent based integrity tests make it difficult to test in situ following sterilization because of the risk of downstream solvent contamination. A newly developed method, the Water Pressure Integrity Test (WPIT), allows for the integrity testing of hydrophobic filters eliminating the problems associated with traditional test methods employing solvents. A prime advantage of WPIT is that it may be performed in situ post sterilization without any downstream manipulations. The test has been directly correlated to the retention of bacterial challenges. Data will be provided to show the reliability and sensitivity of this easy to perform test.


Chemical stability of two sterile, parenteral formulations of cyclophosphamide (Endoxan) after reconstitution and dilution in commonly used infusion fluids. The commercially available parenteral dosage forms of cyclophosphamide (Endoxan, Cycloblastine) are manufactured by an aseptic dry-filling technique and exhibit a slow dissolution rate. A novel dosage form has been developed by one of the manufacturers based on the technique of freeze drying. Dissolution rates of both types of formulations were determined and it was shown that the freeze-dried formulation dissolves more rapidly, within 20 seconds, while it takes at least three minutes to dissolve the dry-filled formulation. The chemical stabilities of the cyclophosphamide solutions, obtained after reconstitution and/or dilution of both formulations, have been investigated and tested as a function of drug concentration (20 and 1 mg/mL), solvent (water, 0.9% sodium chloride, 5% dextrose), container material (glass and polyvinyl chloride (PVC)), light conditions (normal room fluorescent light/dark) and temperature (4 degrees, 20-22 degrees and 37 degrees C). The test solutions were analyzed by a stability-indicating reverse phase high performance liquid chromatographic method with ultraviolet detection at 214 nm. Cyclophosphamide solutions (solvent: water; drug concentration; 20 mg/mL) are stable when stored for seven days at 4 degrees C in the dark. At higher temperatures degradation occurred during the test period with 10% loss after seven days at ambient temperature and 50% loss after seven days storage at 37 degrees C. Similar data were found in admixtures with 5% dextrose and 0.9% sodium chloride and initial drug concentration of 1 mg/mL. There are no significant differences in chemical stability between the solutions obtained from reconstitution and dilution of the dry-filled and lyophilized formulations.(ABSTRACT TRUNCATED AT 250 WORDS)


Temperature profiles and sterilization within a dead-ended tube. Use of steam-in-place (SIP) sterilization has increased as the complexity of biotechnology processing equipment has increased. Extensive biological testing is required prior to use of this equipment as no quantitative guidelines exist for the design of SIP sterilizable equipment. Dead-ended geometries present the most difficult challenge to SIP sterilization, but data are not available as to the effects of tube orientation, length and diameter on time required for sterilization. This study examines the effects on sterilization of location within a dead-ended tube and orientation of the tube with respect to the gravitational vector. Temperature profiles and biological kill of Bacillus stearothermophilus were determined for four tube orientations. Kill kinetics were characterized by time to start of kill and cycle log reduction (CLR) times. Both values increased with increasing distance up the tube and orientation of the tube in a more horizontal position. CLR values were as much as ten times greater than those resulting from saturated steam. Projected sterilization times were determined and found to be very dependent on tube orientation. Recommendations are given for sterilization and validation testing of dead-ended geometries.


Perinatal mortality and morbidity--the Scottish perspective. Although perinatal mortality has continued to fall in Scotland during the last decade, there has been little change during the last three years i.e. 8.9, 8.9, 8.7 per thousand births respectively. Many deaths still result from antepartum haemorrhage and unknown causes so the Scottish Perinatal Mortality group is undertaking a confidential enquiry into the deaths of all normally formed infants of birthweight greater than 2500 g. The other major cause of prenatal death i.e. preterm delivery is also associated with a significant risk of neurological impairment. Results from the Scottish Low Birthweight Study show that 5.7 per cent and 9.5 per cent of very low birthweight infants have severe and moderate disability respectively, reveal once again the importance of research into the primary and secondary prevention of preterm delivery and the care of the preterm neonate.


A comparison of postoperative morbidity following prophylactic antibiotic administration by combined irrigation and intravenous route or by intravenous route alone during cesarean section. This study compared the efficacy of a single intravenous dose of Cefazolin alone or combined with an antibiotic containing preclosure-irrigation solution in patients undergoing cesarean section. A total of 308 patients were prospectively assigned to two groups by randomization. Group I received two grams of Cefazolin IV and abdomino-peritoneal irrigation with saline. Group II received one gram of Cefazolin IV and one gram in the saline irrigation solution. The rate of total postoperative morbidity was 2.3 times higher in Group I compared to Group II (16/154 or 10.4% vs 7/154 or 4.5%) and morbidity at the operative site was six times higher (13/154 or 8.4% vs 2/154 or 1.3%).


The impact of genetic syndromes on children's growth. Genetic syndromes that include short stature are recognized by their effect on children's growth rates, by their effect on the growth rate and pubertal development in adolescence, and by the presence of stigmata associated with certain syndromes. The effects of Down, Seckel, Turner, Russell-Silver, Prader-Willi, and Noonan syndromes on growth and the growth-inhibiting features of achondroplasia, hypophosphatemic rickets, and Laron dwarfism are reviewed. The terminology used by professionals in discussing genetic alterations should minimize the effects of labeling and stigmatization and should emphasize the normal aspects of a child's life.


Differences in somatic and organ growth rates in infants who died of sudden infant death syndrome. The aim of present investigation was to study the changes in weight and external measurements and the rates of growth of the internal organs and to compare these findings in infants who died of the sudden infant death syndrome (SIDS). The subjects were 165 infants (100 males and 65 females) who died in Leningrad in 1983-1989 in the first five months of life. Relative growth rates for each month were calculated for weight, external measurements and organ growth, and their ratio was also calculated. Apparent discordance in growth rates was revealed when contrasting the rates for weight, length, head and chest circumference to the growth rates of internal organs and when compared them with each other. The present data show the relation of specific growth patterns to SIDS.


Routine growth monitoring and assessment of growth disorders. Pediatric nurse practitioners have an important role in the routine monitoring of growth and the assessment of growth disorders. The development of good history-taking skills and an accurate, repeatable measurement technique are central to the success of growth assessment and evaluation. Numerous causes exist for growth disorders. The pediatric nurse practitioner can be instrumental in identifying these disorders and in making appropriate referral to a pediatric endocrinologist for further evaluation and treatment.


A comparison of two commercially irradiated Trypticase Soy Agars containing lecithin and polysorbate 80. Gamma-radiation sterilized Trypticase Soy Agar containing lecithin and polysorbate 80 (TSA++) (Becton Dickinson Microbiology Systems, Cockeysville, MD) and irradiated TSA++ (Adams Scientific, West Warwick, RI) were tested by a quantitative spread plate method. Four bacteria Bacillus subtilis ATCC 6633, Pseudomonas aeruginosa ATCC 10145, Staphylococcus aureus ATCC 25923, Streptococcus pyogenes ATCC 19615 and the yeast Candida albicans ATCC 10231 were tested in two separate experiments using different lots of media. A strain of Aspergillus niger ATCC 16404, was tested by a qualitative streak plate method. The Becton Dickinson Microbiology Systems (BDMS) irradiated TSA++ overall recovered a greater number of organisms than the Adams Scientific TSA++ in both experiments and allowed for the earlier recovery of S. pyogenes ATCC 19615. The growth of A. niger ATCC 16404, was comparable on both media. Efficacy of the media to neutralize 1, 2 and 3% phenol as well as 0.001, 0.01 and 0.1% benzalkonium chloride (BC) solutions was done by a disk diffusion method using 2 gram-positive and 4 gram-negative bacteria. Both media showed complete neutralization of the 0.001 and 0.01% BC solutions and partial neutralization of the 0.1% BC solution. The BDMS TSA++ showed better neutralization of the 2 and 3% phenol solutions than the Adams Scientific TSA++. This data indicates that not all irradiated TSA++ media perform in an equivalent manner.


Formulation development of frozen parenteral dosage forms. Many of the intravenously administered drug compounds are formulated as frozen dosage forms due to lack of sufficient chemical stability at room or refrigerated temperatures. The product is stored in a freezer in the hospital pharmacy and thawed prior to its use. These products therefore, require a long-term frozen shelf-life plus a short-term room temperature and/or refrigerated temperature shelf-life. The formulation is optimized for overall stability in the frozen state as well as in the thawed state. In this paper, the significance of phase changes in the frozen state and the influence of various formulation factors such as drug concentration, diluent, buffer concentration, pH, and raw material purity on the drug stability in the frozen state is reviewed. An overview of analytical and manufacturing considerations unique to frozen products is also presented.


In vitro lymphocyte functions in the presence of bovine surfactant and its phospholipid fractions. Endotracheal administration of human or xenogenic surfactant preparations is an effective treatment of the respiratory distress syndrome of preterm infants. The application of large amounts of phospholipids to the lung may result in a significant alteration of the local immune response. We studied the influence of the bovine surfactant preparation SF-RI 1 (Alveofact) on lymphocyte functions in vitro. PHA-induced cell proliferation and immunoglobulin synthesis in the presence of whole surfactant as well as six different defined phospholipids were investigated. A marked concentration-dependent suppression of immunoglobulin production independent of the immunoglobulin isotype and cell proliferation was observed in the range of 5 ng/ml-3 mg/ml of a single phospholipid (or SF-RI 1 respectively). It could be demonstrated that suppression of lymphocyte functions was only due to the phospholipid content of the surfactant preparation. These data indicate that in vivo immune functions may be significantly altered by the administration of exogenous surfactant. This may be particularly important in the presence of primary or secondary pulmonary infections.


Accelerated growth in children.

Accelerated growth in children. Many tall-statured children will display variations of normal growth patterns, such as familial tall stature or familial rapid maturation. However, precocious puberty and a number of rarer diseases that can cause accelerated growth require the earliest possible detection and treatment to ensure that underlying problems are appropriately treated and optimum final adult height is attained. Most of these syndromes are rare. Nevertheless, the pediatric nurse practitioner should be acquainted with them to make timely and appropriate referrals to endocrinologists, geneticists, cardiologists, or orthopedists.


Calcium dependence of endogenous acetylcholine release into the fetal circulation of the dually perfused human placental lobule. The aim of this study was to examine the role of calcium in the release of acetylcholine (ACh) from the fetal circulation of the dually perfused human placenta. The viability of this preparation was demonstrated; Glucose consumption and lactate production (as sums of both the fetal and maternal values) over the 4 h perfusion period were 13.9 +/- 4.2 mmol/kg/h (mean +/- SEM, n = 7) and 15.1 +/- 2.0 mmol/kg/h (n = 13) respectively. Mean pH levels of the fetal and maternal effluent perfusates were 7.26 +/- 0.02 (n = 5) and 7.32 +/- 0.01 (n = 5). None of these parameters varied significantly from 1 to 4 h of perfusion. ACh output into the fetal vessels after 1 h of perfusion was 0.31 +/- 0.02 nnmol/min/g wt weight (n = 5) in the presence of physostigmine (2.7 uM) and did not vary significantly from 1 to 4 h of perfusion. Perfusion with Ca+(+)-free Krebs solution and 2 mM EDTA (but not with Krebs in the absence of EDTA, or with both Ca++ and EDTA, or in the presence of 3.78 mM Ca++) for 60 min resulted in a significant reduction of ACh output in the fetal perfusate. Output in the former case was partially restored on subsequent perfusion with normal Krebs for 60 min. These results suggest ACh release in perfused human placenta lobules is at least partially Ca+(+)-dependent.


Assessment of infant growth.

Assessment of infant growth. Growth is one of the best indicators of neonatal and infant well being. By comparing the growth of an individual infant over a period of time with available standards, the determination can be made, within limitations, whether the infant is doing as well as should be expected or whether any growth abnormalities exist. The three most common physical measurements of growth are weight, length/height, and head circumference. Normal growth patterns and factors that impact growth within the first 2 years of life are discussed, with recommended techniques for assessment.


Determination of t-PA activity and t-PA antigen in human milk. Although a considerable number of publications on tissue plasminogen activator (t-PA) in human milk have appeared, most investigators have determined t-PA activity using an assay on fibrin plates [1, 2, 3, 4]. We measured t-PA activity by a bioimmunoassay and t-PA antigen by ELISA using a monoclonal antibody (SP-322) [6], and estimated t-PA index ((t-PA activity, ng/ml)/(t-PA antigen, ng/ml) x 100) in human colostrum and milk to evaluate the fluctuations of post-delivery t-PA. The concentrations of t-PA activity decreased slowly related to the duration of lactation varying between days one and two hundred and ten and showed significant negative correlation with the duration (P less than 0.001). The t-PA antigen made a slow descent, followed by a reciprocal ascent of the t-PA index to the fifty eighth post-delivery day and showed significant correlations with the duration (P less than 0.001, P less than 0.05, respectively). This information suggests that a high concentration of t-PA may be released into the narrow channels of the glands functioning to maintain duct patency under the regulation of an inhibitor such as plasminogen activator inhibitor (PAI).


Educational, psychologic, and social aspects of short stature. Children with short stature may experience academic difficulties, psychologic impairment, and emotional stress related to an underlying medical condition or social stigmatization. Educational and psychosocial problems associated with short stature often can be alleviated with appropriate interventions. Parents, health-care practitioners, and teachers should be aware of the potential academic, psychologic, and social problems related to short stature and growth delay, so they can support the short child's normal development and intervene promptly if problems arise.


Fetal breathing movements and prostaglandin levels in pregnancies complicated by premature rupture of the membranes. We have previously demonstrated that maternal and fetal prostaglandin levels may be elevated in patients with pregnancies complicated by premature and prolonged rupture of the membranes (PPROM) compared to patients with intact membranes. In the fetal lamb, infusion of prostaglandin abolishes fetal breathing movements and in human pregnancies with PPROM and with poor outcome, fetal breathing movements are absent. The aim of this study was to determine fetal breathing activity in pregnancies complicated by PPROM which had elevated prostaglandin levels. One-hour ultrasound examinations were performed on nine fetuses whose mothers had had premature rupture of the membranes at 28 weeks gestation and a median of 4 days prior to the ultrasound examination. The number of fetal breathing movements (FBM) and percentage of time that each fetus spent breathing was documented and this was then related to control values. Following the completion of the ultrasound examination, cordocentesis was performed and blood sent for estimation of bicyclo PGEM levels. All of the fetuses made some breathing activity during the one-hour period, but the number of FBM varied from 1 to 181 (median 21). The percentage time that the fetuses spent breathing was much lower than that which would be expected for their gestational age, being a median of 1.3% (range less than 0.1 to 50.8%) of control values. As bicyclo PGEM levels were elevated in these nine fetuses, these data suggest that reduction in breathing activity in fetuses of pregnancies complicated by PPROM may be due to elevated prostaglandin levels.


Femoral artery blood flow monitoring has distinct advantages for examining redistribution of blood flow in fetal acidosis. Changes of blood flow in umbilical artery, carotid artery and femoral artery were examined during the progression of acidemia in fetal sheep by means of indwelling transit-time ultrasonic blood flow meters. Moreover, catecholamines in fetal blood were measured and its interrelation to the alteration in blood flow was examined. Gradually progressing fetal acidemia was induced by repeated cord compression. Umbilical blood flow showed a initial increase thereafter maintaining a plateau through the experiment, which seemed to be dependent on fetal arterial pressure. Carotid artery flow gradually increased until the arterial pH in fetal blood declined to 7.20 and remained at this level even though the acidemia further progressed. Femoral artery flow markedly decreased around fetal arterial blood pH 7.20 and its change correlated well with the plasma level of catecholamines. This change of femoral artery flow may be evaluated by examination of the flow index as well as flow volume. Redistribution of blood flow in the progression of fetal acidemia may be initiated at around fetal arterial pH 7.20 and can be detected by studying femoral artery flow.


Catecholamine abnormalities in transient tachypnoea of the premature newborn. The aim of the present study was to assess if there was an association between low catecholamine levels at birth in the premature infant and the development of TTN. Blood samples were collected at delivery from the umbilical artery of all preterm infants with a gestational age less than 36 weeks for determination of pH and catecholamine levels (noradrenaline and adrenaline). Amongst non-asphyxiated infants only, cord pH greater than 7.25 and/or Apgar score greater than 7 at five minutes, catecholamine levels were compared between the 10 infants who developed transient tachypnoea of the newborn (TTN) and 13 controls of a similar gestational age range (31-35 weeks) who developed no respiratory distress in the neonatal period. Infants who developed TTN were more often delivered without labour, 8 of 10 compared to 2 of 13 controls (p less than 0.01). There were no significant differences in adrenaline levels between the two groups. Noradrenaline levels, however, were significantly lower in the infants who developed TTN, being a median of 3.1 nmol/l (range 1.07-5.85 nmol/l) compared to a median of 6.4 nmol/l (range 2.38-22.83) in the controls (p less than 0.01). Infants who were delivered following labour had significantly elevated noradrenaline levels compared those delivered without labour (elective delivery) (p less than 0.05). These results suggest that low noradrenaline levels in preterm infants may explain the association in this group of TTN and "elective" delivery.


The prediction of fetal compromise and acidosis by biophysical profile scoring in the small for gestational age fetus. In a prospective blind study, 133 fetuses suspected of being small for gestational age (SGA), defined as an estimated fetal weight less than the 10th centile for gestation, were monitored by weekly biophysical profile assessment. Perinatal outcome was assessed by umbilical venous blood pH estimation and compared with the profile score determined within seven days of delivery. The positive and negative predictive values of the full biophysical profile score were not significantly better than combinations of two or three of the individual components in this group of fetuses. The use of amniotic fluid volume, non-stress testing and either fetal movement or breathing offers an acceptable alternative to full biophysical profile assessment in the fetus suspected of being small for gestation.


Human choriogonadotropin (hCG) and placental lactogen (hPL) inhibit interleukin-2 (IL-2) and increase interleukin-1 beta (IL-1 beta), -6 (IL-6) and tumor necrosis factor (TNF-alpha) expression in monocyte cell cultures. The effect of the human trophoblast hormones chorionic gonadotropin (hCG) and placental lactogen (hPL) on the expression of cytokines in peripheral blood mononuclear cell cultures was followed under a variety of culture conditions, (a) phytohemagglutinin stimulated cells (PHA-MSC), (b) allogenic mixed cells (AMC) and (c) spontaneously proliferating cells (SPC). A dose dependent enhanced release of IL-6, IL-1 beta and TNF-alpha by hCG and hPL was observed under all culture conditions. However, an inhibitory effect on the IL-2 release was seen in PHA-MSC by hPL and in AMC by hPL and hCG. The role of the suppression of IL-2 production/release on cytotoxicity towards trophoblast is discussed. These results suggest a sensitive, dose dependent hormonal control of the modulation of the immune response during pregnancy and strengthen the concept of a distinct regulation of monocytes and lymphocyte subpopulation by trophoblast hormones.


Discordant anencephaly with a cleft lip and palate in a pergonal-induced triplet pregnancy. Anencephaly in triplets and pergonal induced pregnancies is a very rare incident. Associated cleft lip and palate has never been reported in these case. In this paper we report the first case of an anencephalic infant with cleft lip and palate in a set of pergonal-induced discordant triplet pregnancy.


Dental implants: a review.

Dental implants: a review. The present article is a review presenting an update on the field of dental implants since the World Workshop in Clinical Periodontics in July 1989. Areas that are discussed include following: 1. Biomaterials and the implant interface, and the interaction of these with the environment. 2. Periodontal considerations including data supporting a perimucosal seal of implant to soft tissue and discussion of the endosseous interface between the bone and the implant. 3. Newer techniques of diagnostic imaging and their determination of bone types are related to the future practice of dental implants. 4. Implant selection and the surgical techniques involved in implant placement. 5. Current ideas of implant prosthodontics, implant maintenance, and the treatment of implant failures. 6. Finally, the use of dental implants in the United States and Sweden.


The effect of certain systemic medications on oral calculus formation. A quantitative comparison was made of supragingival calculus that formed in individuals using systemic medications for defined systemic medical problems and individuals not using medication. Measurements of supragingival plaque and calculus were made on the lingual surfaces of the 4 mandibular incisors of 68 consecutive patients presenting for dental examinations and oral prophylaxes. Variables noted in addition to medication and plaque status were: age, sex, time interval since previous prophylaxis, and smoking status. Analysis of results indicated a statistically significant reduction of calculus among individuals medicated with beta-blockers, diuretics, anticholinergics, synthroid and allopurinol despite the high quantity of plaque present.


Healing of the intrabony periodontal lesion following root conditioning with citric acid and wound closure including an expanded PTFE membrane. The effect of citric acid conditioning of the root surface in conjunction with gingival flap surgery including barrier membranes (expanded polytetrafluoroethylene) was clinically evaluated in 26 intrabony periodontal defects in 23 patients. Control treatment included gingival flap surgery with barrier membranes alone. Twelve defects were treated with the experimental and 14 with the control protocol. Healing was evaluated 12 months after surgery. Initial probing depths approximated 6.9 mm and defect depths measured during surgery exceeded 4 mm. The patients exhibited good oral hygiene over the study interval as substantiated by low plaque and bleeding scores. Acid conditioning of the root surface did not enhance periodontal healing in this study, similar amounts of defect resolution were observed following either treatment protocol. Probing depth reduction generally approximated 1.8 mm; gain of clinical attachment, 0.8 mm; and defect bone fill, 1.2 mm. Under the prevailing conditions, the barrier membrane procedure apparently gave a healing result beyond which further improvement could not be achieved by root surface conditioning.


In vitro effects of citric acid application techniques on dentin surfaces. The present study evaluated the in vitro effects of different application techniques of citric acid on dentin root surfaces. Ten freshly extracted, periodontally involved teeth were obtained and 4 dentin slabs, approximately 4 x 6 x 2 mm, were obtained from the roots of each tooth, for a total of 40 slabs. These slabs were identified by tooth and preserved in 1:1 anhydrous glycerol/absolute alcohol solution. Citric acid pH 1 was applied to 32 of the slabs for 5 minutes with one of 4 different techniques: 1) immersion; 2) placed with a saturated cotton pellet with no rubbing; 3) placed and burnished with a saturated cotton pellet; or 4) applied with a camel hair brush. The remaining 8 dentin slabs were used as negative control specimens, root-planed and non-acid treated. Following the various treatments, the slabs were fixed, dehydrated, critical point dried, and coated for scanning electron microscopic (SEM) evaluation. Scanning photomicrographs were obtained at 2,000, 6,000, and 40,000 magnifications. The surface characteristics of the treated dentin slabs were evaluated descriptively regarding the degree of fiber exposure; the number of exposed tubules and the surface area occupied by tubule orifices were also measured. Friedman's 2-way analysis for block designs was employed. Results demonstrated that root-planed, non-acid treated specimens had an amorphous, irregular surface which corresponded to a smear layer.(ABSTRACT TRUNCATED AT 250 WORDS)


Endotoxin levels in periodontally healthy and diseased sites: correlation with levels of gram-negative bacteria. This study investigated the correlation between endotoxin levels and the percentage of Gram-negative bacteria in healthy sites and in periodontitis sites. Twelve healthy adults participated. Each subject provided 3 periodontitis sites with 5 to 8 mm probing depths that bled on gentle probing and 3 healthy sites with sulcus depths of 1 to 3 mm that did not bleed. Clinical examinations and sterile paper point sampling of all study sites were conducted on days 0, 7, and 14, and site-specific endotoxin levels and percentage of Gram-negative bacteria were determined. There were significant differences in both endotoxin levels and percentage Gram-negative bacteria between healthy and periodontitis sites across all 3 sampling periods, but no difference across sampling periods in the healthy sites and the periodontitis sites, respectively. Correlation coefficients revealed a high degree of correlation between site-specific endotoxin levels and percentage of Gram-negative organisms. Using a sample dilution of 1 x 10(4), endotoxin levels differentiated healthy from periodontitis sites with a specificity of approximately 91% and a sensitivity of approximately 90%.


Comparison of presurgical and immediate postsurgical ibuprofen on postoperative periodontal pain. Previous studies have indicated that non-steroidal anti-inflammatory drugs administered prior to oral surgery procedures are effective in reducing postoperative pain. The purpose of the present study was to compare the efficacy of medicating with ibuprofen immediately presurgically to medicating immediately postsurgically on postoperative pain associated with periodontal surgery. Sixty patients who were to undergo periodontal surgery were randomly divided into 3 groups: the I-pretreatment group received 600 mg ibuprofen immediately presurgically and placebo immediately after the surgery; the I-post-treatment group received placebo before surgery and 600 mg ibuprofen postsurgically; the placebo group received placebo at both time periods. Responses from an 8-hour pain diary completed by each subject were quantified and statistically evaluated non-parametrically. Results indicated that dosing with ibuprofen either immediately before or immediately after periodontal surgery significantly delays onset of pain as compared to placebo, with dosing after surgery demonstrating a significantly greater delay of onset of pain as compared to dosing presurgically. In addition, unlike the presurgical dosing, dosing postsurgically significantly decreases mean pain intensity for a combined 8-hour period following periodontal surgery as compared to placebo.


Guided tissue regeneration versus mucogingival surgery in the treatment of human buccal gingival recession. A surgical technique involving membranes was used to treat localized human buccal recessions 3 mm to 8 mm. The results on 25 patients (test group) were evaluated 18 months postoperatively and compared with the results obtained in 25 other patients (control group) having undergone mucogingival surgery. In the test group, a trapezoidal flap with a large base was raised beyond the mucogingival junction. The exposed root surface was scaled thoroughly to a concave shape. A membrane was bent and adapted onto the concave root surface. The flap was sutured far coronally and the membrane removed one month later. The control patients underwent a 2-step procedure, consisting of a free gingival graft and a coronally positioned flap. The amount of root coverage obtained was similar in the 2 groups (test = 72.73%; control = 70.87%), although the clinical attachment gain (test = 5.12 mm; control = 3.56 mm) and pocket variation (test = 1 mm reduction; control = 0.06 mm increase) differed significantly (P < 0.001). The keratinized tissue width was greater in the control group. The regression analysis showed that the amount of covered root surface after treatment was in strict correlation with the depth of the original recession in the test group, while no correlation was found in the control group. The expected root coverage was greater in the test group when the recession was greater than 4.98 mm, while it was greater in the control group when the recession was less than 4.98 mm. These results indicate that a guided tissue regeneration procedure can be used to successfully treat recession. The membrane procedure compared favorably with the mucogingival surgery in the treatment of deep recession.


A comparison of ePTFE membranes alone or in combination with platelet-derived growth factors and insulin-like growth factor-I or demineralized freeze-dried bone in promoting bone formation around immediate extraction socket implants. The purpose of this study was to compare bone promotion around implants which were augmented with ePTFE membranes alone or in combination with cortical demineralized freeze-dried bone (DFDB) or the combination of platelet derived growth factor-BB (PDGF) and insulin like growth factor I (PDGF/IGF-I). Membranes were placed over titanium implants which had been inserted into fresh extraction sockets with large buccal dehiscences. Twenty-four implants were placed in 4 dogs. At 18 weeks clinical bone height measurements were taken, the animals were sacrificed, and all specimens retrieved for histologic evaluation. Clinically, a significant gain in bone levels was present in both the ePTFE membrane alone group (P < 0.005) and PTFE plus PDGF/IGF-I group (P < 0.01), but not in the PTFE plus DFDB group. Results from histometric measurements revealed an approximately 2-fold increase in the percentage of implant surface in contact with bone, area of bone adjacent to the implant surface, and in the total length of the implant surface in contact with bone in the dehiscence defects treated with ePTFE plus PDGF/IGF-I compared to the defects receiving ePTFE membranes alone (each P < 0.05). The response to the DFDB was highly variable and it did not significantly improve the efficacy of the PTFE membranes for any parameter measured. The distance from the outer surface of the new bone to the implant surface was statistically significant for ePTFE membranes alone and membranes plus PDGF/IGF-I. The results demonstrated that clinically, ePTFE membranes alone or ePTFE membranes with PDGF/IGF-I were equally effective in promoting bone growth around the implants. Histologic measurements demonstrated that sites treated with ePTFE membranes plus PDGF/IGF-I had the highest bone density compared with sites which received ePTFE membranes alone or with ePTFE membranes and DFDB. The results of this study question the use of DFDB and support the use of ePTFE membranes alone or with PDG-F-BB/IGF-I as potential methods of promoting bone formation around dental implants.


Effects of melatonin on water metabolism and renal function in male Syrian hamsters (Mesocricetus auratus). The pineal indoleamine, melatonin, has been shown to influence many physiological systems within the mammalian body. Few studies, however, have examined the influence of melatonin on renal function. This study investigated the effects of melatonin on water metabolism and renal function. Young adult male Syrian hamsters were maintained on a long photoperiod (LD 14:10) in metabolic cages. The animals received daily (1700) injections of either control vehicle or 25 micrograms of melatonin for 85 consecutive days. Melatonin administration resulted in significant increases in water consumption and urine production. Water budgets were also significantly influenced by melatonin, as were urinary osmolality, urinary sodium, and potassium concentrations, but urinary calcium concentrations were essentially unaltered. When excretion rates for sodium, potassium, and calcium were calculated, no differences were observed between the vehicle control and melatonin-treated groups. Injections of melatonin also significantly decreased plasma antidiuretic hormone (ADH). These results demonstrate that afternoon injections of melatonin can alter renal function, which may involve direct (i.e., on ADH secretion and/or thirst mechanisms) or indirect (i.e., behavioral) effects.


Androgenic function in adult rats: influence of the pineal gland of the mother and of the offspring. Female rats exposed to long (LD 18:6) or short (LD 6:18) photoperiods from 21 days of age were mated when they reached 55 days of age. On day 2 of gestation animals of each group were either pinealectomized or sham-operated. Lighting regimens were not changed during the course of the study. Male offspring of the four groups of dams were sacrificed on day 70 after birth. Rats that were maintained on long photoperiod had higher testicular testosterone, androstenedione, and dihydrotestosterone content than those raised on a LD 6:18 cycle. Whatever the breeding photoperiod used, maternal pinealectomy induced no modification of reproductive function. Among rats kept in short photoperiod, neonatal pinealectomy (on day 5 after birth) resulted in an enhanced testicular androgen content without any modification of plasma androgen concentration. These results indicate that (1) the previously reported effect of the mother's pineal on pubertal rat testicular function is not present in adulthood and (2) the pineal of the offspring is required to maintain normal testicular androgen content in the adult rat but exerts no influence on circulating androgens.


Inhibin-like "antigonadotropic" activity in the ovine pineal. In an attempt to define the antigonadotropic activity associated with the protein/peptide extracts of ovine pineals, melatonin- and steroid-free fractions obtained after subjecting crude ovine pineal acetone powder to soft gel chromatography were tested in three bioassay systems: (1) the conventional compensatory ovarian hypertrophy inhibition assay in rats, (2) the coupled bioassay in immature mice that enables one to distinguish factors acting at the level of the pituitary from those acting at the gonadal level, and (3) the classical in vitro pituitary cell culture assay for inhibin. The large molecular weight fraction, referred to as PI, behaved like a classical antigonadotropin as it suppressed compensatory ovarian hypertrophy following unilateral ovariectomy. Further, it not only lowered the basal and gonadotropin releasing hormone (GnRH)-stimulated release of follicle stimulating hormone (FSH) by the cultured pituitary cells, but also inhibited the human chorionic gonadotropin (hCG)-induced uterine weight gain in the coupled assay, thus acting like inhibin in these two assay systems. In addition, it showed immunological cross-reactivity with ovine testicular inhibin. The present results strongly support the view that inhibin-like activity may be the major player in what has so far been referred to as antigonadotropic activity.


Determination of kinetic properties of serotonin-N-acetyltransferase in bovine pineal gland using HPLC with fluorimetric detection. The determination of serotonin-N-acetyltransferase (NAT) activity in the bovine pineal gland and other rat tissues was based upon the separation and detection of N-acetyltryptamine formed from tryptamine and acetyl CoA by means of high performance liquid chromatography with fluorimetric detection. In the bovine pineal the enzyme exhibited a Km value of 31.45 +/- 4.98 microM and a Vmax value of 30.90 +/- 1.18 pmol N-acetyltryptamine/min/mg protein for tryptamine, and a Km value of 28.72 +/- 7.50 microM and a Vmax value of 25.90 +/- 1.50 pmol N-acetyltryptamine/min/mg protein for acetyl CoA. The present method is simple, allows the determination of NAT activity from a variety of enzyme sources, has application to pharmacological studies of NAT regulation in tissue cultures, and provides an alternative to current radioenzymatic assays.


Effect of immunization against melatonin on seasonal fleece growth in feral goats. Four vaccination protocols were utilized to investigate the effects of immunoneutralizing circulating melatonin on the annual cashmere growth cycle and cashmere production in Australian feral goats. A fluctuating anti-melatonin antibody response, achieved by repeated booster vaccinations, resulted in an acceleration of the growth cycle in goats which exhibited a significant immune response, compared to sham-immunized controls. Responding goats showed two cycles of cashmere length growth in the first 16 months and increased annual cashmere production in the first year. However, in the second year, these effects were no longer apparent, suggesting either some form of desensitization to melatonin, or a diminished response due to declining antibody titre. The effects of immunization were observed in both sexes; the effect on cashmere length was greater in wethers than in does. Cashmere fibre growth in response to a continuously declining plane of specific antibody showed increased cycle frequency, albeit with a decreased amplitude; guard hair growth cycles were affected to a much lesser extent. Small transient peaks of specific immunity at the summer or winter solstice were without significant effect on cashmere growth. Immunization to provoke a persistent anti-melatonin antibody response at the winter solstice resulted in significantly increased greasy fleece weight, % cashmere yield, and mass of cashmere produced, but no change in fibre diameter in both sexes. Thus the timing of cashmere growth cycles in goats may be, at least transiently, altered by appropriately timed immunization against melatonin. The mechanism of pineal-mediated regulation of cashmere growth cycles may involve (i) entrainment of an endogenous rhythm by melatonin, or (ii) seasonal alteration of cashmere follicle sensitivity to the effect of melatonin.


Effects of selective histamine receptor antagonists on skin responses to intradermal bradykinin in healthy volunteers. The effects of chlorpheniramine and cimetidine on the cutaneous responses to intradermal injections of bradykinin were investigated in a randomized, double-blind, placebo-controlled, cross-over study. Chlorpheniramine significantly attenuated the increase in cutaneous blood flow and erythema induced by bradykinin but not the weal response. Cimetidine was without influence on these parameters and the effects of the combined therapy of chlorpheniramine and cimetidine were not significantly different from those due to chlorpheniramine alone. These results suggest that the cutaneous vasodilator effect of bradykinin is in part due to histamine release acting on histamine H1-receptors.


Characterization of human immunodeficiency virus-1-infected cells of myeloid-monocytic lineage (ML-1, HL-60, THP-1, U-937). The myeloid-monocytic cells ML-1, HL-60, THP-1, and U-937 were chronically infected (for > 2 years) with the lymphotropic human immunodeficiency virus type 1 (HIV-1) strain HTLV-IIIB. Reinfection experiments revealed that viruses obtained from chronically infected ML-1/HIV-1 and HL-60/HIV-1 cells showed a low infectivity if tested with uninfected ML-1 and HL-60 cells in contrast to virus preparations from chronically infected THP-1/HIV-1 and U-937/HIV-1 with their corresponding uninfected cell lines. Analyses of selected cell surface markers revealed a differential expression of CD4, CD8, CD11c, CD14, CD15, CD20, HLA-DR, and HLA-DQ in non- or chronically infected cells. In chronically infected cells, the steady-state levels for tumor necrosis factor-alpha, interleukin (IL)-1 beta, and granulocyte-macrophage colony-stimulating factor mRNA remained unchanged whereas the one for IL-6 dropped.


Pharmacokinetics of dideoxyinosine in pigtailed macaques (Macaca nemestrina) after intravenous and subcutaneous administration. Four macaques (Macaca nemestrina; 1 female and 3 males) were administered dideoxyinosine (DDI) at three dose levels (3.2 mg/kg i.v., 10 mg/kg i.v., and 20 mg/kg s.c.). Blood and urine samples were collected during 6-8 h and 24 h after drug administration, respectively. The mean plasma clearance (16.7 +/- 4.9 ml/min/kg), steady-state volume of distribution (1.5 +/- 0.4 L/kg), and terminal plasma half-life (96.8 +/- 7.5 min) did not differ significantly between the two i.v. doses. DDI was eliminated from the body primarily by excretion of the unchanged drug in the urine (74%). The absorption of DDI from the subcutaneous site was complete (bioavailability of 0.91 +/- 0.13) and rapid, with peak plasma concentration obtained at 30 min.


Report of a Consensus Workshop, Siena, Italy, January 17-18, 1992. Maternal factors involved in mother-to-child transmission of HIV-1. Although most children with AIDS have acquired HIV from their mothers, transmission from an HIV-infected mother to her infant is neither uniform nor currently predictable. With the rapid worldwide spread of HIV infection, particularly into women of child-bearing age, definition of the risk factors associated with maternal transmission is essential to develop and deliver intervention therapy that might impact on the devastating spread of AIDS. To promote research defining the risk factors of HIV transmission from mother to infant, an international workshop was held on January 17-18, 1992, in Siena, Italy. Epidemiology, immunology, virology, and health issues associated with maternal HIV transmission were actively discussed by participants. Current information from the literature and new data available from laboratories formed the basis for the consensus opinions developed at the meeting. Wide differences (10-39%) in HIV transmission seen at different geographic sites may be explained by multiple risk factors. The timing of transmission of HIV from mother to fetal, newborn, or breast-fed infants may be further complicated by viral burden and other cofactors. There are intriguing suggestions that the immunological status of the mother may be influential in preventing or reducing HIV transmission. But this appears to be interrelated with the HIV viral burden and health status of the mother and in turn her likelihood to transmit HIV to her offspring. The infecting "inoculum" may be low and/or selective because of biological barriers that favor reduced transmission with good health of the mother and the absence of other infectious diseases.


Progressive multifocal leukoencephalopathy in patients with HIV infection: lack of impact of early diagnosis by stereotactic brain biopsy. Thirteen patients with HIV-related progressive multifocal leukoencephalopathy (PML), representing an institutional incidence of 4.2%, are reported. All cases were diagnosed by image guided stereotactic brain biopsy shortly after their presentation for neurologic complaints. All patients were males; risk factors included homosexual or bisexual activity or intravenous drug use. At the time of presentation with PML, the mean T4 count was 85 (range 9-240 cells/mm3). The most common neurologic symptoms were cognitive dysfunction and aphasia, whereas gait abnormalities and disordered cognition were the most common neurologic signs. Cerebrospinal fluid analysis was helpful only to rule out other causes of CNS disease. Magnetic resonance imaging, more sensitive than computed tomography (CT) scanning, typically revealed multiple areas of increased intensity on T2 weighted images although unifocal disease was seen in 23% of patients. Despite early stereotactic biopsy and aggressive symptomatic therapy, survival of these patients was poor with a mean of 2.6 months after the onset of neurological symptoms and 2.0 months after biopsy.


The identification and tracking of Candida albicans isolates from oral lesions in HIV-seropositive individuals. Restriction fragment polymorphism analysis was used to investigate the identity and genotypic relatedness of Candida albicans strains isolated from human immunodeficiency virus (HIV)-infected patients with or without oral candidiasis and from some of their sexual partners. Use of the species-specific DNA probe Ca3 revealed that most subjects carried a single distinct C. albicans strain throughout the course of the study, during both symptomatic and asymptomatic periods. Sexual partners were more likely to carry the same or similar C. albicans isolates than unrelated subjects, raising the possibility of transmission via intimate contact. One patient appeared to acquire his partner's isolate, which then became predominant in both partners in subsequent isolations. These findings indicate that recurrent oral candidiasis is usually caused by a single persistent strain unique to each patient, but that in some cases transmission via intimate contact may occur between sexual partners.


D-xylose malabsorption: characteristic finding in patients with the AIDS wasting syndrome and chronic diarrhea. The AIDS wasting syndrome (AWS) is characterized by > 10% loss of baseline body weight during 6 months and may occur in patients with or without associated chronic diarrhea. To determine whether the presence of small-intestinal malabsorption is associated with the development of AWS in human immunodeficiency virus (HIV)-infected patients with chronic diarrhea, we retrospectively reviewed the results of D-xylose testing performed in the clinical evaluation of 21 consecutive HIV-infected patients with chronic diarrhea. A thorough search for small-intestinal pathogens was performed including upper endoscopy, duodenal biopsy, and aspirate for culture and ova and parasite examination. These studies were negative in all patients except two who were excluded from the study. In the 19 patients with no identifiable pathogens, the 1-h serum D-xylose concentration was significantly lower in patients with AWS than in those without, 8.3 +/- 0.8 versus 23.7 +/- 3.4 mg/dl, respectively, p < 0.001. Urine D-xylose excretion during 5 h was also significantly lower in the group with AWS, although creatinine clearance was similar in the two groups. Patients with AWS were more often refractory to standard antidiarrheal therapy with loperamide or diphenoxylate and carried a poor prognosis (90% mortality at 1 year versus 22% mortality in the group without AWS). These data indicate that small intestinal malabsorption is a major component in the severe wasting seen in some HIV-infected patients with chronic diarrhea. Patients with markedly abnormal D-xylose tests may require more potent antidiarrheal therapy and are expected to have a high mortality as a possible consequence of intestinal dysfunction.


Pneumocystis carinii choroiditis in patients with AIDS: clinical features, response to therapy, and outcome. To further characterize the clinical features, response to therapy, and outcome of Pneumocystis carinii choroiditis in patients with AIDS, we retrospectively reviewed the course of choroiditis for eight patients identified from two institutions through April 1991. Seven patients had prior Pneumocystis carinii pneumonia and had received aerosolized pentamidine prophylaxis for a median of 10 months; one patient had no prior history of pneumonia or prophylaxis. The median CD4+ lymphocyte count for six patients was 11 cells/mm3. Choroiditis was a preterminal diagnosis for three patients--two with associated disseminated pneumocystosis. Ocular manifestations improved or resolved with therapy for five of the six treated patients. All five subsequently received prophylaxis with dapsone (n = 2), dapsone/trimethoprim (n = 2), or aerosolized pentamidine (n = 1). Choroiditis recurred at 15 months in the one patient receiving aerosolized pentamidine. The median survival from time of diagnosis was 44 weeks. A literature review including an additional 40 cases support the conclusions that (a) Pneumocystis choroiditis is a rare complication of advanced HIV disease, occurring often in the context of systemic pneumocystosis; (b) ocular signs and symptoms may improve or resolve with specific antipneumocystis therapy; and (c) relapse may occur, particularly in those not receiving systemic prophylaxis.


Rhodococcus equi cavitary pneumonia in HIV-infected patients: an unsuspected opportunistic pathogen. Two patients seropositive for human immunodeficiency virus (HIV) and with no previous acquired immunodeficiency syndrome-defining conditions developed cavitary pneumonia and pleural disease caused by Rhodococcus equi. R. equi was isolated from these patients' sputum and lung biopsy specimens, respectively, but the microorganism was initially considered to be a contaminant (patient 1) or misidentified as a nontuberculous mycobacterium (patient 2). The R. equi infection was fatal in one patient, who died after 4 months without specific antimicrobial therapy; the second patient was unresponsive to combination therapy with various antimicrobial agents. R. equi may cause life-threatening infections in HIV-infected patients. Microbiology laboratories should be cognizant of the need to exclude R. equi as a cause of infection in highly immunosuppressed patients.


HIV disease and AIDS in women: current knowledge and a research agenda. The study of the clinical manifestations, progression, and outcome of human immunodeficiency virus (HIV) infection in women has begun in earnest. AIDS-defining diseases that are more common in women than in men include wasting syndrome, esophageal candidiasis, and herpes simplex virus disease, whereas Kaposi's sarcoma is rare. Non-AIDS-defining gynecological conditions such as vaginal candida infections and cervical pathology are prevalent among women at all stages of HIV infection. Associations have been documented between the presence of human papillomavirus, lower genital tract neoplasia, and HIV-related immunosuppression. Pregnancy has not been confirmed to have an effect on the clinical progression of HIV disease in women incremental to the effect of time. Differential access and utilization of therapeutic interventions appear to account for much of the reported gender discrepancy in survival. Well designed epidemiological and clinical studies will help further scientific knowledge leading to early diagnosis, appropriate treatment, and timely prevention of the manifestations of HIV disease in women.


HIV-1 and HIV-2 infections in a high-risk population in Bombay, India: evidence for the spread of HIV-2 and presence of a divergent HIV-1 subtype. A high-risk population (patients of a sexually transmitted disease clinic and the GT hospital in Bombay) was tested for antibodies against HIV-1 and HIV-2. Among 405 serum samples, 226 had previously been classified HIV-positive in India using different locally available enzyme-linked immunosorbent assay (ELISA) tests. The serology of 179 samples was unknown. All 405 samples were tested at the Georg-Speyer-Haus (GSH) with the Pasteur HIV-1/2-Combi-ELISA. Positive samples were further analyzed with HIV-1 and HIV-2 Western blot kits from Dupont and Pasteur, respectively. A very high seroprevalence of HIV was found in this population. Among the 179 unscreened samples, 69 (38.5%) were positive in the ELISAs as well as the Western blots for HIV-1 or HIV-2. Among the prescreened samples, only 174 (77%) were confirmed HIV-positive. Altogether, 243 of 405 sera were HIV-positive. Of these, 184 (76%) were reactive with HIV-1, 10 (4%) were reactive with HIV-2, and 49 (20%) had dual reactivity to HIV-1 and HIV-2. Previous data from the Indian Council of Medical Research had already suggested a possible high prevalence of HIV-1 in India. Our results confirm this view. The finding of a substantial spread of HIV-2 infection was, however, totally unexpected in India, but confirms our previous study which had already demonstrated the existence of HIV-2 in this country. Asia can thus no longer be considered free of HIV-2, and testing for HIV-2 appears mandatory, at least in India.(ABSTRACT TRUNCATED AT 250 WORDS)


Variations in inpatient mortality for AIDS in a national sample of hospitals. In this project, we examined the spectrum of AIDS-related conditions and variations in associated inpatient mortality for AIDS patients treated in a national sample of hospitals. We identified 10,538 adult discharges with a diagnosis indicating AIDS from 258 hospitals from a national sample of 438 acute-care hospitals with 6 million discharges in 1986-1987. Opportunistic and other infections occurred in 55.9 and 37.9%, respectively, of AIDS discharges, and inpatient fatality rates varied considerably depending on complication type(s) and comorbidities. Clinical conditions were more important predictors of inpatient death than demographic or treatment site characteristics. Among opportunistic infections, odds of inpatient death were significantly increased for progressive multifocal leukoencephalopathy (odds ratio [OR] = 2.8), Pneumocystis carinii pneumonia (OR = 2.4), cryptococcosis (OR = 1.6), atypical mycobacterial infections (OR = 1.6), and toxoplasmosis (OR = 1.3). Odds of inpatient death were also significantly increased by non-AIDS-defining infections causing septicemia (OR = 3.1) or CNS involvement (OR = 1.6) or pulmonary involvement (OR = 1.5). After controlling for clinical conditions, significant differences in odds of death persisted across regions, age, and ethnic groups. Increases in hospitals' AIDS treatment experience were associated with a significant decrease in odds of inpatient death. These analyses provide a national perspective on the diversity of AIDS-related clinical conditions and their relative effects on inpatient mortality.


The significance of western blot assays indeterminate for antibody to HIV in a cohort of homosexual/bisexual men. The Multicenter AIDS Cohort Study. The objective of this study was to determine the frequency and significance of nondiagnostic Western blot (WB) assays in homosexual/bisexual men at risk of infection with HIV-1. The presence of a positive enzyme-linked antibody assay (EIA) confirmed by a positive WB was used as evidence of infection and seroconversion. Indeterminate WB assays were defined as reactions to only one viral gene product of HIV-1. Three analyses were conducted to (a) determine the frequency of such reactions in men who, during a 4-year period, did not develop diagnostic serologic reactions; (b) determine, retrospectively, the preseroconversion frequency of indeterminate WB assays in 286 men who seroconverted; and (c) evaluate in vitro production of specific antibody by peripheral blood mononuclear cells (PBMCs) as a method of indicating whether or not an indeterminate WB assay represents HIV-1 infection. Reactions to products of gag, pol, or env were noted in 8.0, 4.0, and 6.7% of 1,595 first-visit tests of men who remained seronegative for 4 years. Indeterminate reactions occurred in 204 men with negative EIAs who subsequently seroconverted and in 82 men with positive EIAs preconversion. Supernatants harvested from PBMCs of 2 of 36 seroconverters obtained one or two visits preseroconversion and cultured with pokeweed mitogen were antibody-positive. All were positive at the visit, with diagnostic serology. None of the supernatants from cells of 19 men with EIA-negative WB-indeterminate serologic assays were antibody-positive. Our results suggest that persistently EIA-negative homosexual/bisexual men who have indeterminate WB assays are unlikely to be infected with HIV-1.(ABSTRACT TRUNCATED AT 250 WORDS)


Inhibition of HIV-1 RNA production by the diphtheria toxin-related IL-2 fusion proteins DAB486IL-2 and DAB389IL-2. Productive infection of cells by human immunodeficiency virus type 1 (HIV-1) is associated with the activation state of the cell and its obligatory expression of the interleukin-2 receptor (IL-2R), the latter providing a new target for antiviral therapy. A quantitative RNA-RNA hybridization assay is employed to detect production of HIV-1 RNA and to show that two IL-2 diphtheria toxin-related fusion proteins (DAB486IL-2 and its more potent, truncated form DAB389IL-2) inhibit HIV-1 RNA production in infected cells. A mutant form of DAB486IL-2 containing a single point mutation that inactivates the adenosine diphosphate ribosyltransferase activity of the toxin does not inhibit HIV RNA production, even though the molecule binds to the IL-2R. The active fusion proteins inhibit viral RNA replication in cells infected with HIV-1 clinical isolates as well as with a ZDV-resistant strain of HIV-1. These results indicate that IL-2 receptor-targeted fusion proteins can be utilized to inhibit HIV-1 replication effectively in infected human lymphocytes.


HIV-1 LTR activation model: evaluation of various agents in skin of transgenic mice. Mice containing the HIV-1 long terminal repeat (LTR) regulating the expression of firefly luciferase reporter gene were investigated for their use as a model for activation of the LTR. As a limited test of this model, a number of different factors were screened for their ability to affect reporter gene activities in the skin. Reporter gene levels were increased in the skin by topical treatment of dimethylsulfoxide, retinoic acid, phorbol ester, ultraviolet light, and hydrogen peroxide, all of which have previously been shown to cause increased HIV production in cultured human cells. Topically applied arachidonic acid, histamine, ethanol, acetone, and methanol did not increase reporter gene activities. A lack of published reports on activation of HIV-1 in human cells by these agents suggests that they do not activate viral expression in human cells, which corroborates with the findings of this report. Minor forms of skin wounding and intraperitoneally administered psoralen plus ultraviolet light also increased reporter gene activities in skin. Control and test treatments could be performed on the same mouse and repetitive samples could be obtained from each treatment area. These transgenic mice might be useful as predictive models for regulation of the LTR in epidermal or dendritic cells.


Longitudinal study of homosexual couples discordant for HIV-1 antibodies in the Baltimore MACS Study. Thirty-six sexually active couples serologically discordant for human immunodeficiency virus, type 1 (HIV-1), within the Baltimore Multicenter AIDS Cohort Study (MACS) were assessed to determine whether evidence of HIV-1 infection could be detected in the HIV-1-antibody-negative partners and whether factors associated with lack of transmission of HIV from the seropositive to the seronegative partner could be ascertained. Six HIV-1 seropositive couples and 18 seronegative couples were followed concurrently for comparison. None of the seropositive subjects had an AIDS-defining illness at entry into the study, and all subjects were followed for 1 year. A separate evaluation of unprotected anal receptive and insertive intercourse between discordant couples indicated high-risk activities for a median of 40 months, as reported by the HIV seropositive partner. Despite this finding, none of the HIV-1 seronegative men in discordant couples had evidence of HIV-1 infection by viral culture, p24 antigen testing, or polymerase chain reaction for HIV-1 DNA. Discordant seronegatives and seropositives did not differ from concordant seronegatives and seropositives in numbers of circulating CD4, CD8, and natural killer lymphocytes or in prevalence of antibodies to herpes simplex virus, type 1, Epstein-Barr virus, or cytomegalovirus, except that discordant seronegative men were less likely than their seropositive partners to have antibodies to herpes simplex virus, type 2. The reason for the apparent lack of HIV-1 infection in seronegative discordant individuals remains unexplained and did not appear to be associated with type of sexual activity, T-lymphocyte subsets or natural killer cells, or early stage of HIV-1 disease.


A simplified surveillance case definition of AIDS derived from empirical clinical data. The Clinical AIDS Study Group, and the Working Group on AIDS case definition. A clinical AIDS case definition is needed for surveillance in countries where the CDC case definition is not practical. To derive such a definition, we compared 110 HIV-seropositive and 135 randomly selected HIV-seronegative adult medical-ward inpatients in Brazil. Multivariate analysis of clinical signs and symptoms and simple diagnoses resulted in a discriminant function with sensitivity of 89% and specificity of 96% in predicting for AIDS. These data were the empirical basis for a clinical definition of AIDS in adults drafted in a Caracas, Venezuela, workshop sponsored by the Pan American Health Organization. The revised "Caracas" definition presented here requires a positive HIV serology, the absence of cancer or other cause of immunosuppression, plus > or = 10 cumulative points, as follows: Kaposi's sarcoma (10 points); extrapulmonary/noncavitary pulmonary tuberculosis (10); oral candidiasis or hairy leukoplakia (5); cavitary pulmonary/unspecified tuberculosis (5); herpes zoster < 60 years of age (5); CNS dysfunction (5); diarrhea > or = 1 month (2); fever > or = 1 month (2); cachexia or > 10% weight loss (2); asthenia > or = 1 month (2); persistent dermatitis (2); anemia, lymphopenia, or thrombocytopenia (2); persistent cough or any pneumonia except TB (2); and lymphadenopathy > or = 1 cm at > or = 2 noninguinal sites for > or = 1 month (2). This definition has a sensitivity of 95% and a specificity of 100% (91% without HIV serology) when applied to the Brazilian patients in this study. The Caracas definition has been adopted by Brazil, Honduras, and Surinam, and is in validation elsewhere. The use of a reasonably sensitive and specific case definition commensurate with available diagnostic resources should facilitate AIDS surveillance in developing countries.


HIV neutralization assay using polymerase chain reaction-derived molecular signals. Characterization of the capacity of human polyclonal antibody to neutralize wild-type patient isolates has important implications for vaccine development. We report the development of a polymerase chain reaction-based neutralization assay that quantitatively measures each infection using HIV proviral formation. These molecular end points identified the absence or quantitative diminution of DNA provirus formation as well as a delay in the kinetics of HIV DNA provirus formation. Using both laboratory strain prototype isolates (HIV-1-MN, HIV-IIIb) and primary wild-type patients' isolates, neutralization end points were reproducibly determined. End points were reached within 72 h, thereby minimizing the impact of subsequent rounds of infection on interpretation of results. Although the neutralization titer of polyclonal sera was usually comparable using standard technology, this assay did find isolate-dependent variation in the relationship between p24 production and HIV proviral DNA formation. Finally, we noted the disparity between the ability of human sera to neutralize prototype and wild-type isolates in primary peripheral blood mononuclear cell targets. We believe this assay provides unique opportunities to characterize the initial events of virus-antibody interaction and will help to elucidate clinically relevant neutralization immunoregulatory mechanisms.


Drug hypersensitivity reactions and human immunodeficiency virus disease. Drug hypersensitivity reactions are often observed by clinicians treating patients infected with the human immunodeficiency virus (HIV). For certain drugs, the incidence of these reactions appears to be higher than previously reported in the general population. The best example is trimethoprim-sulfamethoxazole, associated with rash, fever, hematologic disturbances, transaminase elevation, and, less frequently, more severe reactions, including Stevens-Johnson syndrome, toxic epidermal necrolysis, and anaphylactic-like reactions. Other sulfa congeners, pentamidine, antituberculosis regimens containing isoniazid and rifampin, amoxicillin-clavulanate, clindamycin, and thalidomide also have been associated with an increased incidence of adverse reactions, some of which could involve allergic mechanisms. Effective dosage and management strategies are needed to prevent or ameliorate hypersensitivity reactions when they occur.


Tumor necrosis factor-alpha in advanced HIV infection in the absence of AIDS-related secondary infections. The effect of HIV infection on the production of tumor necrosis factor-alpha (TNF-alpha) was examined in patients with advanced human immunodeficiency virus (HIV) infection in the absence of AIDS-related secondary infections. Serum TNF-alpha and TNF-alpha production in vitro were measured by enzyme-linked immunosorbent assay in 26 male homosexuals with CDC stage IV HIV infection without active AIDS-related secondary infections. In vitro TNF-alpha production was assayed from cultured peripheral blood mononuclear cells (PBMs) or whole blood cultures under conditions for minimising endotoxin contamination. PBMs and whole blood were cultured with and without lipopolysaccharide (LPS). Results were compared with those for 13 HIV-seronegative age- and sex-matched controls. Serum TNF-alpha concentrations were 5 +/- 16 pg/ml in HIV-infected patients and 12 +/- 17 pg/ml in controls. TNF-alpha levels in unstimulated cultures of PBMs obtained from patients were 426 +/- 511 pg/ml and 456 +/- 428 pg/ml in control cultures. There was no difference between groups in the maximal responses of cultured PBMs to stimulation with LPS (2,229 +/- 1,593 pg/ml vs. 2,504 +/- 961 pg/ml). TNF-alpha levels from unstimulated and LPS-stimulated whole blood cultures were not significantly different after adjusting for the number of cultured monocytes (2,038 +/- 1,469 pg/ml vs. 1,511 +/- 488 pg/ml). In 10 patients (38%) the TNF-alpha levels from stimulated whole blood cultures were greater than the 95% confidence interval of the control group. TNF-alpha levels in patients were not significantly altered by antiretroviral therapy.(ABSTRACT TRUNCATED AT 250 WORDS)


The visiting needs of critically ill patients and their families. The purpose of this article is to provide an overview of completed studies that consider visitors in critical care areas. Studies from coronary care, intensive care, pediatric PACUs, and adult PACUs are reviewed.


Comparison of nurses' and family members' perceived needs during postanesthesia care unit visits. Today, more PACUs are opening their doors to visiting family members. This change can be exciting and challenging for the PACU nurse. The expertise involved when caring for the patient must be also extended to the family. Literature shows that families have identifiable needs. By attending to those needs, the nurse may help decrease stress for the family during the patient's hospitalization and enable everyone to cope more effectively. Limited published research is available regarding the needs of family members of PACU patients. This descriptive study explores and compares needs identified by family members when visiting PACU patients with needs of these family members perceived by PACU nurses. Analysis of data using the Mann Whitney-U Test indicates a significant difference between the groups. PACU nurses believed that family members' most important need was information. Family members stated that the need to see the family member was more important than was perceived by the nurses. Both groups agreed that education was an important need. Further studies using a larger sample are needed to validate findings of this study.


Alternate methods of teaching: use of self-learning packets. Self-directed learning takes multiple forms, all of which allow a person to study at an individual pace and direction. By applying principles of adult learning and various other styles of learning, self-directed learning can be used as an alternative method of education. The focus of this article is one type of self-directed learning, self-learning packets. The step-by-step process of designing a self-learning packet is covered. Various methods of topic selection and the key components of self-learning packet design are included. Finally, the usefulness of alternative methods of education such as self-learning packets is examined by cost analysis.


The use of temperature as a discharge criterion for ambulatory surgery patients. Evaluating each patient's return to an acceptable state after surgical and anesthetic intervention is the responsibility of the postanesthesia nurse. Postanesthesia nurses use criteria to determine ambulatory surgical patient readiness to be discharged from phase I recovery to phase II recovery and from phase II recovery to home. Temperature is one indicator of postanesthesia recovery. Temperature discharge criteria from phase I postanesthesia recovery have been reported. However, temperature discharge criteria for phase II postanesthesia recovery have been adapted from phase I standards and nursing traditions. This study sought to describe the postoperative temperatures of ambulatory surgical patients from admission to phase II postanesthesia recovery to discharge home. A convenience sample of 101 adult patients undergoing surgery at a hospital-based ambulatory surgical unit (ASU) participated. Tympanic temperature was measured preoperatively on admission to the ASU, postoperatively, at the beginning of phase II postanesthesia recovery, and at the end of phase II postanesthesia recovery immediately before discharge home. All subjects were normothermic during phase II postanesthesia recovery, with temperatures ranging from 36.0 degrees C (96.8 degrees F) to 38.3 degrees C (101 degrees F). Paired Student's t Test showed significant differences (P < .0001) between temperature means. There was a 0.38 degrees C (0.7 degree F) decrease between preoperative admission temperature and temperature on admission to phase II postanesthesia recovery. During phase II postanesthesia recovery the mean temperature increased 0.16 degree C (0.3 degree F) before discharge home. However, the clinical and practical implications of these findings is questionable.(ABSTRACT TRUNCATED AT 250 WORDS)