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Purpose: To explore the experiences of fathers of infants newly diagnosed with severe congenital heart disease., Design: An analysis of qualitative data collected as part of a larger longitudinal study of parenting the medically fragile infant., Participants: Eight fathers whose infants were hospitalized for severe congenital heart disease, were technology dependent at time of enrollment, and were expected to have serious chronic health problems at discharge. DATA COLLECTION MEASURES: Semistructured interviews in the hospital and the home until the child reached 15 months adjusted age., Results: Findings indicate that fathers experience four interrelated conflicting reactions: the joy of seeing the child born and becoming a father, plus the sadness and loss associated with the baby's illness; the challenge of becoming attached while dealing with fears about the infant's vulnerability and potential death; the need to try to maintain control while feeling a loss of control; and the struggle to remain strong for others while hiding their intense emotions. These findings extend the previous limited research about fathers by identifying the unique conflicts fathers of seriously ill infants experience in coping with the child's diagnosis and treatment. Findings have implications for intervening with fathers during the early diagnostic phase of a serious illness, particularly serious congenital heart disease.

An outbreak of El Tor biotype cholera occurring in a rural village in Irian Jaya, Indonesia was evaluated for risk factors associated with death from cholera. Among those dying in the village during the epidemic, a significant association between membership in one of the five tribal groups in the village complex was associated with an elevated risk of suffering a cholera death (odds ratio = 5.9). Interviews with members of the decedents' families revealed a very strong association (odds ratio = 11.6) between risk of cholera death and having attended the two day funeral of a woman who died of a cholera-like illness a few days prior to an outbreak of cholera-like diarrheal disease in the village complex. Recent flooding may have contributed to the creation of an environment conducive to cholera transmission.

Superoxide anion (O2-) plays a key role in the endogenous suppression of endothelium-derived nitric oxide (NO) bioactivity and has been implicated in the development of hypertension. In previous studies, we found that O2- is produced predominantly in the adventitia of isolated rabbit aorta and acts as a barrier to NO. In the present studies, we characterize the enzyme responsible for O2- production in the adventitia and show that this enzyme is a constitutively active NADPH oxidase with similar composition as the phagocyte NADPH oxidase. Constitutive O2--generating activity was localized to aortic adventitial fibroblasts and was enhanced by the potent vasoconstrictor angiotensin II. Immunohistochemistry of aortic sections demonstrated the presence of p22(phox), gp91(phox), p47(phox), and p67(phox) localized exclusively in rabbit aortic adventitia, coincident with the site of staining for O2- production. Furthermore, immunodepletion of p67(phox) from adventitial fibroblast particulates resulted in the loss of NADPH oxidase activity, which could be restored by the addition of recombinant p67(phox). Further study into the regulation of this adventitial source of O2- is important in elucidating the mechanisms regulating the bioactivity of NO and may contribute to our understanding of the pathogenesis of hypertension.

High-resolution capillary electrophoresis sizing of preformed complexes of bis-intercalating fluorescent dyes with double-stranded DNA has been demonstrated using hydroxyethylcellulose and 3-[tris-(hydroxymethyl) methylamino]-1-propanesulfonic acid-tetrapentylammonium (Taps-NPe+4) buffers (S. M. Clark and R. A. Mathies, Anal. Chem. 69, 1355-1363, 1997). Such capillary electrophoresis separations were unattainable in conventional buffers containing other cations such as Tris+, Na+, and NH+4. We report here the behavior of preformed double-stranded DNA-dye complexes on agarose slab gel electrophoresis in 40 mM Taps-NPe+4, 1 mM H2EDTA, pH 8.2. Upon electrophoresis in this buffer (a) complexes formed at DNA base pairs:dye ratios ranging from 100:1 to 5:1 show the same mobility; (b) the half-lives of DNA-dye complexes with monointercalators are two- to threefold longer than those in commonly used Tris buffers; (c) there is little dye transfer between labeled and unlabeled DNA molecules; and (d) precise two-color sizing of preformed restriction fragment-dye complexes with fluorescent bisintercalators is achieved.

Adults with acne represent an increasingly important population of acne sufferers referred for treatment. Acne, in these patients, is generally mild or moderate in severity but tends to be resistant to conventional antibiotic therapy. A study was carried out to assess the efficacy of intermittent moderate dose isotretinoin as a treatment for acne. Eighty consecutive patients, over the age of 25 years, referred with acne unresponsive to, or relapsing rapidly after three or more courses of conventional antibiotic therapy were recruited. Acne severity was assessed on the face, chest and back using the Leeds grading scale and the number of inflamed lesions was counted at the site showing the highest acne grade. The patients were 22 men and 58 women. The treatment regimen consisted of isotretinoin, 0.5 mg/kg per day for 1 week in every 4 week for a total period of 6 months. Seventy-five patients completed the study. The therapy was very well tolerated with mild cheilitis as the only side-effect. At the end of treatment, both total acne grade and lesion counts were significantly reduced (P < 0.0001). The acne had resolved in 68 (88%) patients. Twelve months after treatment, acne grades and inflamed lesion counts remained significantly improved (P < 0.0001) in the 68 patients who responded; however, 26 (39%) patients had relapsed. There was a significantly higher incidence of relapse in patients with predominantly truncal acne (P = 0.01). Patients who relapsed also had a significantly higher total acne grade, lesion count (P < 0.0001) and sebum excretion rate (P < 0.001) compared with those whose acne resolved. This study suggests that intermittent moderate dose isotretinoin may be a cost-effective alternative to full dose isotretinoin in a carefully selected group of adult patients with-acne. Selection criteria should include predominantly facial acne, total acne grade less than 1, inflamed lesion count less than 20 and sebum excretion rate less than 1.25 micrograms/cm2 per min.

Methods have been developed for performing accurate, high-resolution, multiplex capillary electrophoresis separations of dsDNA using dimeric intercalation dyes as noncovalent labeling reagents. The quality of these separations is highly dependent on the cation present during electrophoresis. Using buffers that contain only one cation, we show that the tetrapentylammonium (NPe(4)(+)) ion results in high-resolution, high-sensitivity separations but that smaller ions such as sodium or the commonly used buffer ion tris produce low-resolution, low-intensity separations of DNA-dye complexes. Using an 80 mM taps-NPe(4), 1 mM H(2)EDTA, pH 8.4, 0.8% HEC separation buffer, high-quality multiplex separations were performed using TOTO and buTOTIN, YOYO and TOED2, and TO and buTOTIN labeled restriction digests. In the taps-NPe(4) buffer, there is no significant mobility shift when complexes are formed with DNA-dye ratios from 100 to 5 bp per dye and very little dye transfer was observed. This property permits accurate multiplex sizing of samples having a wide concentration range simply by mixing the DNA with a dye solution before electrophoresis. This capability is demonstrated by diluting unpurified PCR products 10-, 100-, and 1,000-fold before mixing with a 1 nM TOTO solution and separating these samples with a ΦX174 HAEIII sizing ladder complexed with buTOTIN. Sizing precisions of better than 1% were obtained at all concentrations of target DNA. The mechanism for the increased DNA-dye complex stability and electrophoretic resolution in the taps-NPe(4) buffer is discussed.

Acne is usually recognized as a disorder of adolescence. However, the referral of patients over the age of 25 years with acne has significantly increased over the past 10 years. The clinical features of 200 patients over the age of 25 years, referred to our department for treatment of acne, were evaluated with a view to establishing possible aetiological factors. There were 152 (76%) women and 48 (24%) men. The mean age of the patients was 35.5 years (range 25-55 years). The acne was mild or moderate in severity, consisting principally of inflammatory lesions, with mean total acne grade (Leeds Grading Scale) of 1.125 for men and 0.75 for women. Most patients had persistent acne; but true late-onset acne (onset after the age of 25 years) was seen in 28 (18.4%) of women and four (8.3%) of men. Thirty-seven per cent of women had features of hyperandrogenicity. One hundred and sixty-four patients (82%) had failed to respond to multiple courses of antibiotics, and 64 (32%) had relapsed after treatment with one or more courses of isotretinoin. External factors, such as cosmetics, drugs and occupation, were not found to be significant aetiological factors. A family history revealed that 100 (50%) of patients had a first-degree relative with post-adolescent acne. Patients with post-adolescent acne appear to represent an increasingly important population of acne sufferers. External factors do not seem to have a significant aetiological role. Two main clinical groups were identified: those with persistent acne and those with late-onset acne. A minority of women also had features of hyperandrogenicity. These patients, and those with late-onset acne, may represent a subgroup who have underlying abnormalities of ovarian, adrenal or local androgen metabolism, and require separate investigation.

The design, construction and operation of a four-color capillary array electrophoresis scanner are presented. The use of sensitive energy transfer primers facilitates four-color detection of the DNA sequencing fragments following excitation at a single laser wavelength (488 nm). This scanner collects fluorescence data from up to 25 capillaries in parallel. The resulting four-color image files are automatically reduced to four-color line plots, and a base-calling program (Sax) is used to call the sequence. The performance of this system for DNA sequencing is demonstrated by examining twelve different motifs of the hypervariable region I of human mitochondrial (mt) DNA obtained from a Sierra Leone population.

Periodontal files are used by many dentists for instrumentation of root surfaces as a part of periodontal treatment. The purposes of this study were: 1) to examine, evaluate, and compare several periodontal files in 3 different conditions: new, used, and used/sharpened and 2) to evaluate the efficacy of 5 sharpening devices. The main characteristics observed included: the number, shape, and interval of blades; the active, rake, and lip angles; changes induced by wear; the influence of sharpening; and the type of metal surfaces comprising the blades. There was a wide range of active angles on each individual file, from a high of 75 degrees to a low of 51 degrees. The range of active angles for all blades on all new files was even greater, from a high of 87 degrees to a low of 30 degrees. Wear, observed on some but not all blades, was not extensive and appeared either as abrasion or, occasionally, as fracture of the blade edge. Sharpness scores (5 = sharpest and 1 = dullest) for new file blades were also extremely variable and spanned the full range of values, with a majority of blades scoring 3.5 and below. Attempts to sharpen files with several devices produced inconsistent results. All 5 sharpening devices had significant shortcomings. It was concluded that the extreme ranges both in active angles and in sharpness scores probably have a significant influence on effectiveness of root instrumentation.

A need for the computer simulation of hydration/dehydration processes in functional aluminosilicate structures has been noted. Full and realistic simulations of these systems can be somewhat ambitious and require the aid of interactive computer graphics to identify key structural/chemical units, both in the devising of suitable water-ion simulation potentials and in the analysis of hydrogen-bonding schemes in the subsequent simulation studies. In this article, the former is demonstrated by the assembling of a range of essential water-ion potentials. These span the range of formal charges from +4e to -2e, and are evaluated in the context of three types of structure: a porous zeolite, calcium silicate cement, and layered clay. As an example of the latter, the computer graphics output from Monte Carlo computer simulation studies of hydration/dehydration in calcium-zeolite A is presented.

The effects of the Luxar LX-20 CO2 dental laser on resected apical root dentin were examined using stereomicroscopy and scanning electron microscopy. The surfaces of 2-mm-thick sections of dentin from freshly extracted human teeth were exposed to CO2 laser radiation. Fluences used ranged from 2.1 to 625.0 J/cm2. The effects of the laser energy on the dentin ranged from no visible effects, to charring, cracking, cratering, and glazing. The most dramatic effect was cracking. Cracking was evident on all specimens having any visible modification of the dentin. A prototype-curved laser tip was used and compared with a standard straight tip. The curved tip did not deliver laser energy to the dentin as efficiently as a straight tip. CO2 laser radiation did not consistently obliterate dentin tubules.

Fluorescence-detected capillary electrophoresis separations of phi X174/HaeIII DNA restriction fragments have been performed using monomeric and dimeric intercalating dyes. Replaceable hydroxyethyl cellulose solutions were used as the separation medium. Confocal fluorescence detection was performed following 488-nm laser excitation. The limits of DNA detection for on-column staining with monomeric dyes (ethidium bromide, two propidium dye derivatives, oxazole yellow, thiazole orange, and a polycationic thiazole orange derivative) were determined. The thiazole orange dyes provide the most sensitive detection with limiting sensitivities of 2-4 amol of DNA base pairs per band, and detection of the 603-bp fragment was successful, injecting from phi X174/HaeIII samples containing only 1-2 fg of this fragment per microliter. Separations of preformed DNA-dimeric dye complexes were also performed. The breadth of the bands observed in separations of preformed DNA-dimeric dye complexes is due to the presence of DNA fragments with different numbers of bound dye molecules that can be resolved as closely spaced subbands in many of our separations. The quality of these DNA-dye complex separations can be dramatically improved by performing the electrophoresis with 9-aminoacridine (9AA) in the column and running buffers. The optimum concentrations of 9AA for the separation of complexes preformed with the dimeric dyes TOTO, EthD, TOTAB, and YOYO were determined to be 100, 1, 1, and 0.5 microM, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Early postburn duodenal feeding can provide adequate nutritional support despite increased risk of intolerance in a severely injured pediatric patient. A 3-year-old girl was admitted with 30% total body surface area thermal burns and sever inhalation injury. During admission, a pediatric feeding tube was placed into the duodenum, and enteral feeding was initiated within 12 hours after injury. Total enteral feeding provided full nutritional needs by postburn day 5 and continued to provide stable and adequate nutrition throughout administration. A full-strength isotonic formula with high concentration of dipeptides and tripeptides was used. Complications of enteral feeding did not prevent achievement of positive caloric and protein balance or repletion of nutritional stores with conscientious nutritional management. Maintenance of admission weight was achieved. This case report describes techniques in nutritional monitoring to assist in optimizing enteral nutrition management.

Prenatal correction of certain cardiac lesions with a poor prognosis may have advantages over postnatal repair. For this to be done, safe and effective support of the fetal circulation must be devised. Studies involving fetal cardiac bypass have demonstrated progressive fetal hypoxemia, hypercapnia, and acidosis, indicating placental dysfunction. We performed fetal cardiac bypass in 18 fetal lambs (126 to 140 days' gestation) to assess the effect of flow rate on fetal oxygenation and metabolism and function of the placenta as an in vivo oxygenator. Fetal cardiac bypass was done for a 30-minute study period at normothermia in all fetuses. During the study period the fetal aorta was cross-clamped and cold cardioplegia was administered to the heart so there was no fetal cardiac contribution to systemic output. Nine fetuses underwent studies at low flow rates (109 +/- 20 mL.kg-1.min-1) and 9 at higher flow rates (324 +/- 93 mL.kg-1.min-1). At the lower flow rate, mean aortic pressure, arterial pH, and oxygen tension decreased whereas carbon dioxide tension and lactate levels increased when compared with prebypass levels. At the higher flow rate mean aortic pressure, pH, oxygen tension, carbon dioxide tension, and lactate levels remained similar to prebypass levels during the 30-minute study period. When the animals were weaned from the bypass circuit after studies at high flow rates, arterial oxygen tension and pH decreased whereas carbon dioxide tension increased to levels similar to those in the low-flow group.(ABSTRACT TRUNCATED AT 250 WORDS)

Computers now offer physicians a wide range of time-saving and cost-effective means of user-friendly access to medical literature. This article describes different methods of using the computer to find information on a subject, focusing on end-user services that provide access to MEDLINE. The different systems available and their respective advantages and disadvantages are described. Use of electronic bulletin boards, Internet and online publishing in medicine also are addressed.

A new method for performing high-speed, high-throughput sizing of DNA has been developed. Samples containing DNA restriction fragments between 70 and 10,000 base pairs in length are electrophoretically separated using capillary arrays in approximately 20 min and detected with high sensitivity using a fluorescence detection system. The separations of phi X174/HaeIII fragments are performed on an array of seven 100-microns i.d., 350-microns o.d. capillaries using replaceable hydroxyethyl-cellulose solutions as the sieving medium. The fragments are fluorescently labeled using ethidium bromide in the running buffer and detected with a laser-excited, confocal-fluorescence scanner. The limit of detection is approximately 1 pg of DNA per band and separations can be detected injecting DNA samples as dilute as 0.1 ng/microliters. Samples were electrokinetically injected from a cassette of microcentrifuge tubes using a format that will facilitate the application of capillary electrophoresis to separations in molecular biology. The feasibility of extending this technique to lower DNA concentrations and to approximately 100 capillary arrays is discussed.

A 38-year-old woman presented with a 10-month history of postprandial abdominal pain and weight loss. She smoked two packs of cigarettes a day, but her history did not indicate diabetes mellitus, hyperlipidemia, or hypercoagulability. A lateral aortogram documented complete occlusion of all three mesenteric arteries but showed no evidence of atherosclerosis, arteritis, or medial fibroplasia. Two retrograde aortomesenteric grafts, one to the superior mesenteric artery and another to the meandering mesenteric artery, utilizing the greater saphenous vein were placed. Pathologic examination of the inferior mesenteric artery demonstrated changes that were considered diagnostic of thromboangiitis obliterans. We found only 10 confirmed cases of thromboangiitis obliterans involving the mesenteric vessels in the English language literature. The present case appears to be the first involving a woman and the only one in which the main trunk of all three mesenteric vessels was involved.

The study was designed to evaluate whether root surface debridement with a sonic scaler plastic insert would cause less pain and discomfort to patients than an ordinary, probe-shaped metal sonic insert. One quadrant in each of 23 patients was debrided with each insert. Blood pressure, mean arterial pressure, and heart rate were monitored before, during, and immediately after each treatment. Pain was also evaluated on a visual analogue scale (VAS) after each treatment, as well as 2 weeks later following pain-provoking stimuli. Blood pressure, mean arterial pressure, and heart rate did not reveal any differences between quadrants treated with plastic or metal inserts. Heart rate had a weak, positive association with treatment time. The VAS gave a higher pain score for the plastic (30.8) than for the metal insert (24.4), but this difference was not statistically significant (P = 0.055). Following pain-provoking stimuli at the 2-week follow-up visit, quadrants debrided with the metal insert (31.3) scored significantly lower (less pain) (P < 0.01) on the VAS than quadrants treated with the plastic insert (30.7). It is concluded that the sonic metal insert caused less pain and discomfort to the patients due to its superior accessibility and water spray cooling. The significant difference between metal and plastic tip debrided quadrants at the follow-up visit was probably caused by the smearing effect of the metal insert with partial closure of the dentin tubule orifices.

This study examined by scanning electron microscopy the effect of various mechanical and chemical procedures in obliterating dentinal tubuli. Dentin blocks containing open, cross-sectioned dentinal tubuli were separated into one experimental and one control area. The mechanical treatments consisted of 20 seconds of continuous instrumentation with sharp and dull curets, finely textured inserts for the EVA reciprocating handpiece, metal and plastic inserts for a sonic scaler, and metal inserts for an ultrasonic scaler. Chemical treatments included a light-cured dental resin and active obliterating agents including sodium, stannous and hydrogen fluorides, potassium oxalate, glycerin, ferric oxalate, and potassium nitrate. These substances were applied to the test surfaces for 2 minutes and allowed to dry. One half of the chemically treated specimens were then sprayed with water in order to evaluate the retention of the obliterating agents. The results revealed that among the mechanical treatments, the sharp curet gave the most consistent and complete obliteration of the tubuli. The plastic inserts had no tubular occluding effects. Among the chemical procedures, the light-cured resin resulted in the most complete obliteration of the tubuli, while the fluoride agents and glycerin had no effect. It can be hypothesized that combining instrumentation with a sharp curet causing a heavy smear layer and occlusion of tubuli apertures, followed by application of a light body resin, may prove to be a rational method of desensitizing hypersensitive dentin surfaces. However, this combined treatment should be evaluated in clinical trials.

The past few years have seen a tremendous renaissance in biological optical microscopy, mainly as a result of the application of digital image processing and video imaging techniques. We review recent developments in microscopy that are permitting unprecedented views of biological structure and function.

The purpose of this study was to assess the effect of citric acid and tetracycline HCl application to dentin surfaces by a "passive dripping" or an "active burnishing" technique. Twenty dentin blocks were prepared from freshly extracted non-diseased human impacted third molars. The blocks were root planed and randomly assigned to two groups for treatment with either citric acid or tetracycline HCl. The duration of treatment was 30, 60, 120, or 240 seconds. Control blocks were treated with distilled water. After treatment the blocks were processed for observation and measurements in the scanning electron microscope (SEM). Application of either of the acid solutions resulted in removal of the smear layer. Measurements indicated a time dependent increase in the mean dentinal tubule orifice diameter ranging from 1.05 microns in control specimens to 3.18 microns after 4 minutes treatment (citric acid group). The increase in tubule diameter was significantly greater (P less than or equal to 0.01) for both citric acid treatment modalities than tetracycline HCl treatment. There was also a time dependent increase in the depth of penetration as measured by a trumpeting of the tubule profiles, and this penetration was significantly greater (P less than or equal to 0.01) after citric acid treatments. Passive or active application of the acids did not seem to have any major impact on the measurements or on the surface morphology. It was concluded that citric acid causes more extensive changes than tetracycline HCl and that the mode of application of the agent is probably not critical.

The standard treatment of innominate artery compression of the trachea has been innominate artery suspension, but the syndrome can recur when this technique is used. From October 1985 until March 1991, 29 infants and children were treated for this syndrome by innominate artery reimplantation. In all patients severe anterior vascular compression of the trachea was demonstrated preoperatively by bronchoscopy and in 17 the diagnosis was confirmed by magnetic resonance imaging scanning. Indications for operation included apneic episodes in 17 (58.6%), severe stridor in seven (24.1%), recurrent bronchopulmonary infections in four (13.8%), and exercise-induced stridor in one (3.4%). Through a median sternotomy, the innominate artery was reimplanted more proximally on the ascending aorta and to the right of the trachea. In this new position, the innominate artery no longer crosses the trachea anteriorly, and the anatomic cause of tracheal obstruction is completely eliminated. There were no early or late deaths, and 27 of the 29 patients (93%) had complete resolution of symptoms. Partial resolution of symptoms was seen in two patients (7%). Reimplantation of the innominate artery offers a unique method by which the anatomic cause of tracheal compression is eliminated. It is a safe and effective means of treating symptomatic compression of the trachea by the innominate artery.

In 32 collections, two larvae, 33 nymphs, and one adult female Ixodes cookei Packard were collected from humans in West Virginia from August 1987 to May 1990. Most were attached. The ticks were found in 14 counties and were the most abundant Ixodes found biting humans. One nymphal I. cookei was removed from the left axilla of a 39-yr-old woman who lives and works in Monongalia and Marion counties, W. Va. The bite was the center of an expanding erythematous lesion reaching 4 cm in diameter, clearing centrally, and typical of erythema migrans. This association and the near absence of Ixodes dammini Spielman, Clifford, Piesman & Corwin from the state suggests the possibility that I. cookei may be an important vector of Lyme borreliosis in West Virginia. In five separate collections, five nymphal Ixodes dentatus Marx were removed from humans in four counties, implicating this species as a potential minor vector of Lyme borreliosis in West Virginia.

This study explored adolescent age and gender differences in patterns of emotional self-disclosure to parents and friends. The sample consisted of 174 junior high school students between the ages of 12 and 15. Results revealed that females exhibited greater emotional self-disclosure to parents and peers than did males, and that emotional self-disclosure to friends was greatest among older adolescents. In addition, while younger adolescents preferred to disclose information about their emotional state to parents, older adolescents chose friends. Exploratory hierarchical regression analyses revealed that emotional disclosure to parents was most strongly associated with adolescent perceptions of the openness of family communication, family cohesion, and satisfaction with family relationships. Emotional disclosure to friends was associated with adolescent self-esteem in the peer context and identity development. The results are discussed in terms of the complementary socializing processes that may operate within the contexts of family and friends.

We report here a system for automation of the dideoxynucleotide DNA sequencing method. The system consists of a Beckman Biomek 1000 robotic workstation which has been modified by the addition of a thin heater/cooler block directly on the instrument table. The heater/cooler block, which is regulated by a user-specified program integrated into the Biomek software, facilitates the use of both single- and double-stranded DNA sequencing procedures. Using this system, we are able to perform 24 sets of dideoxynucleotide DNA sequencing reactions in approximately 45 min. The reactions are performed in 96-well microtiter plates, using a prepared reagent pack which includes primer, enzyme, nucleotide mixes and radioactive label. Using standard gel electrophoresis technology, we are able to resolve over 500 nucleotides per sequencing reaction in about 5 h. Currently, we are able to perform three runs of 24 samples each, with subsequent gel analysis per 8-h period. Excluding autoradiography, this represents a daily data output of 36,000 base pairs.

A new instrument has been developed for the electrophoretic separation of large DNA molecules that can independently regulate the voltage of each of 24 electrodes and allow the magnitude, orientation, homogeneity, and duration of the electric field to be precisely controlled. Each parameter can be varied at any time during the electrophoretic process. Thus distinct sets of conditions can be combined to optimize the separation of various fragment sizes in a single run. Independent control of electrode voltage allows all of the fields to be generated with electrodes arranged in a closed contour, independent of a particular geometry. This device increases both the resolution in any size range and the speed of separation, especially for DNA molecules larger than 3 megabases.

The Office of Medical Applications of Research of the National Institutes of Health conducted a survey to evaluate the effectiveness of mass mailing of consensus statements as compared with traditional dissemination methods. The consensus statement on osteoporosis, published earlier in JAMA, was selected for study. Physicians (N = 695) within each of five relevant specialties in two comparable metropolitan areas were surveyed. Findings suggest that while a small but significant increase of awareness resulted from direct mailing, this increase should be weighed against costs and effectiveness of other methods.

There is long-standing controversy as to whether fever capacity is reduced in aged man. Although loss of this cardinal sign of disease would be an impediment to diagnosis and treatment, there has been no previous research on altered febrile responses using aged primate models. In the present experiments the febrile reaction to IV Salmonella typhosa endotoxin was reduced in monkeys over 14 years old and in one-third of those 10-14 years of age compared with that of younger animals. In response to injections of endotoxin into the lateral cerebral ventricle (ICV), animals over 10 years old showed small or no fevers. Injections of probenecid (ICV), an inhibitor of central inactivation of leukocytic pyrogen and prostaglandin, augmented fever caused by IV and ICV endotoxin and hyperthermia caused by ICV PGE2 in animals under 10 years of age. However, in older animals probenecid increased fever caused by ICV endotoxin only, although the increased response was still less than one quarter that of younger animals. The results indicate that old squirrel monkeys have decreased febrile responses that may be traced to alterations in central sensitivity to pyrogens.

Increased sensitivity to certain drugs is believed to contribute to dysthermia in the elderly. To learn whether the temperature-altering effects of an opiate are increased in aged primates, injections of morphine sulfate (0.5-4 mg/kg) were given SC in randomly assigned order to squirrel monkeys ranging in age from 3.5 to over 17 years. Hyperthermia was the predominant response with no clear relationship to age, although hypothermic and biphasic responses also occurred, most commonly after the highest dose. Lateral cerebral ventricular injections of 0.625 and 1.25 micrograms morphine sulfate evoked hyperthermia in monkeys over 8 years of age but did not affect the temperature of animals less than 5 years old. Doses of 2.5 and 5 micrograms usually elicited hyperthermia regardless of age, but 10 micrograms induced hypothermia in a majority of monkeys. Naloxone was given intraventricularly to several monkeys to limit the degree of hypothermia after high doses of morphine given peripherally or centrally. Thus in these primates, as in other species such as the rat, lower doses of morphine usually evoked hyperthermia, but sufficiently high doses caused body temperature to fall. Unlike the case in the squirrel monkey with diazepam and with endogenous substances such as leukocytic pyrogen and taurine, there was not a strong or consistent relationship between age and morphine-induced temperature changes.

Quantitative measurement of DNA migration in gel electrophoresis requires precisely controlled homogeneous electric fields. A new electrophoresis system has allowed us to explore several parameters governing DNA migration during homogeneous field pulsed field gel (PFG) electrophoresis. Migration was measured at different switch times, temperatures, agarose concentrations, and voltage gradients. Conditions which increase DNA velocities permit separation over a wider size range, but reduce resolution. We have also varied the angle between the alternating electric fields. Reorientation angles between 105 degrees and 165 degrees give equivalent resolution, despite significant differences in DNA velocity. Separation of DNA fragments from 50 to greater than 7000 kilobases (Kb) can easily be optimized for speed and resolution based on conditions we describe.

Hypothermia was produced by IM administration of diazepam (0.125-0.5 mg/kg) to squirrel monkeys of various ages (2-16 years) in a thermoneutral (23 +/- 0.5 degrees C) environment with animals over eight years of age having slightly greater responses. Hypothermia caused by an intermediate dose (0.25 mg/kg) was augmented in a cold environment (15 degrees C), especially in the older animals. There was no marked alteration in the temperature change/age regression after 0.25 mg/kg diazepam in a hot environment (30 degrees C) compared with the control response. Injections of diazepam (1.25-5.0 microgram) into the lateral cerebral ventricle in a thermoneutral environment produced hyperthermia rather than hypothermia in all animals, and the magnitude of the induced hyperthermia was smaller in older monkeys. The results support previous case reports in man and suggest that this commonly used drug can induce hypothermia, especially in older primates exposed to cold. The drug action responsible for this temperature change appears to take place peripherally rather than within the brain.