A prospective, randomized, controlled comparison of retrobulbar and general anesthesia for strabismus surgery.

A prospective, randomized controlled study (n = 95) was conducted to compare the morbidity and length of hospital stay associated with retrobulbar neuromuscular blockade (LA) with that associated with general anesthesia (GA) for monocular strabismus surgery in adult patients. A scoring system was developed to assess postoperative nausea and vomiting, pain, level of consciousness, oral intake, and activity while in the hospital and for the first 3 postoperative days. There was no significant difference in the postoperative nausea and vomiting associated with the two anesthetic techniques. Although patients receiving LA experienced less immediate postoperative discomfort (P < .01) and had greater levels of activity (P < .0001) while in the hospital, the discomfort and activity levels of the two groups were similar at home. The LA group was discharged from the hospital sooner (mean, 135 minutes vs 250 minutes; P < .001), allowing more efficient use of hospital resources. Both techniques provided excellent anesthesia for monocular strabismus surgery.


Indirect ophthalmoscope argon laser treatment of retinoblastoma.

We describe our use of an indirect ophthalmoscope argon laser for the treatment of selected retinoblastomas. The essential aspect of the technique is the creation, using the "continuous" exposure setting, of a confluent white laser burn completely around the tumor base. This procedure results in the prompt regression of most tumors, although several sessions, 1 to 4 weeks apart, are usually necessary for all but the smallest lesions. This method of laser treatment is applicable to retinoblastoma tumors located anywhere in the ocular fundus, including ones adjacent to the ora serrata.


Fellow eyes in idiopathic macular hole cases.

The fellow eyes in 84 cases of unilateral idiopathic macular hole were studied retrospectively to determine prognoses and risk factors for this disorder. On initial examination, 15 of 84 eyes (18%) had a macular cystic lesion (group 1), 23 (27%) had a yellow spot in the fovea (group 2), and 46 (55%) had a normal macula (group 3). Of the 84 eyes, 58 (69%) had posterior vitreous attachment. During a mean follow up of 39 months, macular hole developed in 8 of 15 eyes (53%) in group 1, and in 6 of 23 eyes (26%) in group 2. However, a macular hole did not develop in eyes with posterior vitreous separation or a normal macula. Although the risk of developing a macular hole may have been overestimated in our study, posterior vitreous attachment and macular abnormalities may be important in predicting macular hole formation in the fellow eyes in idiopathic macular hole cases.


Ocular integrity after refractive surgery: effects of photorefractive keratectomy, phototherapeutic keratectomy, and radial keratotomy.

The effects on ocular integrity of three surgical techniques to correct refractive errors were compared. Ten matched pairs of eyes (right and left eyes) freshly enucleated from pigs underwent radial keratotomy (RK) (four incisions, 3.50-millimeter clear zone) in one eye and photorefractive keratectomy (PRK) with the 193-nanometer excimer laser (10.00- diopter myopic correction, 6.00-millimeter ablation diameter) in the fellow eye. Another 16 eyes under- went phototherapeutic keratectomy (PTK) at various depths; another 10 eyes were used as controls. All eyes were subjected to lateral compression by a bench press, with gradually increasing pressure applied until the globe ruptured. The rupture site was photographed. Of the 10 control eyes, 9 ruptured at the sclera and 1 ruptured at the optic nerve. All eyes that had undergone RK ruptured at the sites of the corneal incisions, whereas the eyes that had PRK ruptured at the sclera (P < .01). After PTK, corneal rupture upon compression occurred when ablations were about 40% depth or greater. Corneas that have been subjected to PRK thus appear less predisposed to rupture due to blunt trauma than do eyes that have undergone RK.


Modified SRK formula for axial myopia (24.5 mm < or = axial length < 27.0 mm).

When used for eyes with greater than average axial length (AXL), the SRK formula has been reported to have a tendency to yield more myopic refractions than those predicted. To further evaluate such findings, we studied 609 eyes with AXLs between 24.5 and 27.0 mm. Comparing the predicted with the actual refractions and calculating the range of errors, we found that the postoperative refractions were more myopic than predicted. Then, based on our evaluation of the relationship between the postoperative refractions and the powers of the implanted intraocular lenses (IOLs), we devised the following formula: R = 0.8 x (P - I) + 0.57 (P < .01) in which R = the postoperative refraction; P = the emmetropic IOL power; and I = the actual IOL power. Testing this modified SRK formula in 55 additional eyes, we found that the predicted postoperative refractions it yielded were more accurate than those calculated using five earlier formulas.


Visual results and complications following posterior iris-fixated posterior chamber lenses at penetrating keratoplasty.

We retrospectively reviewed the records of 13 patients with pseudophakic bullous keratopathy who had undergone penetrating keratoplasty combined with suturing of a posterior chamber intraocular lens (PC-IOL) with angulated haptics to the posterior iris using the four optic positioning holes. Corneal endothelial decompensation was associated with anterior chamber IOLs in nine cases, with iris-fixated lenses in three cases, and a subluxated PC-IOL in one case. Visual acuity was 20/40 or better in 46%, 20/50 to 20/100 in 31%, and 20/200 or worse in 23%. These visual results are comparable with those reported for other similar surgical series. In four of seven eyes that had preoperative peripheral anterior synechiae (PAS), postoperative extension of at least 2 clock hours occurred; progressive angle-closure glaucoma developed in two of the four. In all four eyes, the extension occurred in the region directly overlying the lens haptics. The angulated haptics of iris-sutured PC-IOLs may predispose to extension of PAS and development of progressive angle-closure glaucoma.


Long-term follow up of argon laser trabeculoplasty in pigmentary glaucoma.

Nine eyes in nine patients with pigmentary glaucoma were treated with argon laser trabeculoplasty (ALT). The mean age of the patients at the time of treatment was 35 years (range, 25 to 46 years); the mean follow up after treatment was 5.5 years. The initial pressure-lowering effect of ALT was 53% (15.3 mm Hg), ie, from a preoperative mean of 29.0 mm Hg to a postoperative mean of 13.7 mm Hg the day after ALT. However, the initial response to ALT wore off in 3 months, after which the intraocular pressure settled at a level 14% (4 mm Hg) lower than before treatment. The rate of failure (ie, unstable glaucoma after treatment) was 11%.


Corneal surface after deepithelialization using a sharp and a dull instrument.

Manual removal of the corneal epithelium currently precedes excimer laser photorefractive keratectomy. To assess the smoothness of the corneal surface following this procedure, six paired human eye-bank eyes (12 eyes) were manually deepithelialized using a blunt instrument (Paton spatula) on one eye and a sharp instrument (surgical blade) on the contralateral eye; all deepithelializations were done by the same surgeon. The 12 corneas were then resected and processed in an identical fashion for scanning electron microscopy. The microphotographs obtained showed that among the corneas deepithelialized with the blunt spatula, two had a smooth surface, and four had variable amounts of residual epithelial cells and basement membrane, confirmed by light microscopy. The surface of five corneas deepithelialized with the sharp instrument were slightly rougher than the former, with occasional linear scratches; one cornea retained a small amount of basement membrane. Removal of epithelium appears to be more complete when a sharp instrument is used. These findings may have clinical relevance, since residual epithelium and basement membrane after deepithelialization may influence the depth of ablation subsequently achieved with the excimer laser.


The pH of antibiotic vitreous infusion combinations: a potential cause of retinal toxicity.

Experiments were undertaken to measure the pH of solutions of commonly used intravitreal antibiotics in various irrigating solutions to determine whether a change in pH might be a factor in antibiotic-induced retinal toxicity. Such retinal toxicity has been particularly damaging when solutions of gentamicin have been used. The pHs of the following solutions were measured: gentamicin, amikacin, methicillin, tobramycin, and vancomycin, combined with balanced salt solution (BSS) PLUS (bicarbonate buffer), BSS (citrate/acetate buffer), and lactated Ringer's solution (lactate buffer). Each of these antibiotics induced a concentration-dependent decrease in pH of the solutions; gentamicin, amikacin and tobramycin produced the largest shifts. The results also demonstrated that BSS PLUS acts as the strongest buffer and lactated Ringer's as the weakest. We conclude that it is important to determine the pH of intraocular antibiotic irrigating solutions, not just the pH of the antibiotics.


Secondary cataract in infants after extracapsular cataract extraction and anterior vitrectomy.

Two infants developed secondary cataract after undergoing extracapsular cataract extraction (ECCE), posterior chamber intraocular lens (IOL) implantation, posterior capsulectomy, and anterior vitrectomy. A similar complication developed in a third child, who had undergone ECCE and posterior capsulotomy. The secondary cataracts developed in these patients from 3 to 12 weeks after the primary operation. In infants, unlike adults, posterior capsulectomy and anterior vitrectomy after ECCE do not seem always to prevent secondary cataracts. In infants, the complication may be related to IOL implantation.


Surgical management of incarcerated retina in the sclerotomy.

We used perfluoroperhydrophenanthrene (Vitreon) to release an incarcerated retina successfully from the pars plana sclerotomy site.


The effect of the laryngeal mask airway on coughing after eye surgery under general anesthesia.

Twenty-nine patients scheduled for elective eye surgery under general anesthesia were randomized into two groups, A and B. After induction of anesthesia, the airway of those in group A was maintained with a conventional tracheal tube; in group B, with a laryngeal mask airway. In the immediate postoperative period, 13 of the 14 patients in group A coughed; none of those in group B did (P < .001).


Accommodative intraocular lens with spring action--Part 2. Fixation in the living rabbit.

After cataracts in 10 eyes of 8 pigmented or albino rabbits had been removed by phacoemulsification, a specially designed 10.0 x 8.5-millimeter accommodative intraocular lens with spring action ("spring IOL") was implanted through a 4.5- to 5.0-millimeter "dumbbell" linear anterior capsular opening. The average follow up was 11 +/- 8 months. All the spring IOLs were almost completely fixed in the capsular bag, and the anterior and posterior capsules remained transparent. However, due to limitations specific to the rabbit, no accommodative power could be detected; also, we observed lens epithelial cells and subsequent fibrous production proceeding from the equatorial area into the area between the optics.


Blepharoptosis induced by prolonged hard contact lens wear.

The authors attempt to establish a relation between hard contact lens wear and upper eyelid ptosis. This study consists of two parts. In the first part, the authors compare the unilateral or bilateral ptosis that developed during hard contact lens wear in 17 patients with the involutional ptosis that developed in another group of 73 patients. In the second part, the authors compare both upper and lower eyelid position in 46 patients who had been wearing hard contact lenses for at least 10 years with the position of 50 matched controls who had never worn contact lenses. The ptosis that had developed in the 17 patients who wore hard contact lenses was clinically similar to that caused by involutional levator disinsertion. The second part of the study shows that the prolonged wearers of hard contact lenses had upper eyelids that were lower by approximately 0.5 mm when compared with control subjects. This difference is statistically significant. According to standard criteria, there were at least 10 ptotic eyelids in the contact lens group versus 1 in the control group. The study findings suggest that prolonged hard contact lens wear may induce a lower position of the upper eyelid and eventually lead to ptosis through levator disinsertion.


Current techniques for the repair of complex orbital fractures. Miniplate fixation and cranial bone grafts.

Computerized imaging of complex fractures of the orbit and facial skeleton have brought about demands for methods of anatomic restoration. In this article, the author outlines techniques for metallic rigid anatomic fixation of facial fractures and the cranial bone graft method of augmentation. Clinical results of fracture repair using various types of metallic plates and replacement of missing bone with cranial bone grafts are presented and techniques are described. Rigid three-dimensional fixation of the facial skeleton with metallic plate fixation and augmentation with cranial bone grafts has produced more predictable correction of severe fractures of the orbit and facial skeleton.


Epithelioid hemangioendothelioma of the orbital bones.

The authors report a case of an epithelioid hemangioendothelioma arising in the orbital bones. A review of the literature related to this rare orbital neoplasm identified eight well-documented cases, one of which occurred in a patient younger than that reported here, but none of which originated in bone. A 3 1/2-month-old boy had a left inferior orbital mass that had grown rapidly over a 3-day period. An emergency computed tomography scan showed a large neoplasm with significant bone destruction of the zygoma and maxilla. Initial examination suggested a rhabdomyosarcoma, and a transconjunctival biopsy was performed, which was complicated by significant blood loss. The final pathologic diagnosis was an epithelioid hemangioendothelioma, or grade 2 hemangioendothelioma, of bone origin. No other sites of disease were found on metastatic survey. Subsequent treatment consisted of an en bloc tumor resection sparing the orbital soft tissues and globe. The patient is free of disease and has normal visual fixation and ocular motility 20 months after surgery. Epithelioid hemangioendothelioma, a vascular malignancy of endothelial cell origin, very rarely involves the orbit. This case is notable for its early development, rapid growth, bony origin, and epithelioid histology.


Polaroid photoscreening for amblyogenic factors. An improved methodology.

The authors describe a new photoscreening camera designed to detect amblyogenic factors, including strabismus, asymmetric and abnormal refractive errors, and media opacities. The photoscreener uses eccentric photorefraction principles and provides two meridian photographs of the retinal reflex. Pass/fail screening data from the photographs of 202 nondilated children as determined by two masked observers were compared with data from complete ophthalmologic examinations. The photoscreener had a sensitivity rate of 87%, a specificity rate of 89%, a positive predictive value of 93%, a negative predictive value of 80%, and an overall agreement rate of 88%. The prescreening probability for amblyogenic factors was 63%. Constant strabismus was detected in all cases. Five intermittent strabismus cases were missed. Two patients with myopia, three patients with hyperopia, and five patients with astigmatism were missed. All media opacities were detected. This new two-flash photoscreening camera, which uses high-speed Polaroid film, is an accurate, reliable method of detecting amblyogenic factors in undilated children. The camera offers promise as a useful mass screening tool.


Lipofuscinosis of the cornea. A clinicopathologic study of three cases.

Lipofuscin pigments are the indigestible residue of lysosomal activity usually associated with normal aging. Abnormal amounts of lipofuscin also are associated with certain disease processes. The rarity of lipofuscin in the cornea and the similarities between its staining properties and those of intracellular micro-organisms caused great diagnostic problems in three cases. The correct diagnosis of corneal lipofuscinosis was made after extensive histochemical, autofluorescent, and ultrastructural studies. Clinical histories of three patients are correlated with morphologic and histochemical findings on five corneal buttons with lipofuscinosis. The histopathologic features of one cornea with chronic keratitis and three corneas from two patients with bilateral opacities of undetermined origin were mostly similar. Large amounts of lipofuscin pigment were found within macrophages and stromal keratocytes. Other pathologic findings were nonspecific, including phagocytosis of degenerated collagen fibrils, scarring, and neovascularization of the stroma. The lipofuscin deposits are probably the consequence of a corneal degenerative process and not its cause, although their pathogenesis remains unclear. Familiarity with the morphologic appearance of corneal lipofuscinosis and its staining and autofluorescent properties is important because the small, 1- to 3-microns deposits may be mistaken for intracellular micro-organisms.


Inhibition of corneal epithelial wound healing. A comparative study of mitomycin C and 5-fluorouracil.

The purpose of this study is to assess the influence of the antiproliferative agents, 5-fluorouracil (5-FU) and mitomycin C (MMC), on the intact corneal epithelium and on epithelial wound healing in the rabbit cornea. Using an eye cup made of polymethylmethacrylate, the intact rabbit corneas were bathed for 5 or 15 minutes with either MMC (in concentrations of 0.0016%, 0.008%, 0.04%, and 0.2%) or 5-FU (in concentrations of 1% and 5%). The same concentrations of MMC or 5-FU were applied to the cornea with the eye cup in which epithelial cells were mechanically removed. The contralateral fellow eyes, which were bathed in balanced salt solution in the eye cup, had the cornea intact or mechanically abraded and served as controls. Five to six animals were used only once for each concentration of MMC or 5-FU. Neither MMC nor 5-FU caused any discernible changes in the intact cornea of any of the eyes. The epithelial healing was retarded by mitomycin in a dose-related manner, and ID50 was calculated to be 0.06%. Five-fluorouracil 5% significantly delayed epithelial healing, but 1% failed to do so. Mitomycin C was estimated to be at least 125 times as potent as 5-FU in inhibiting corneal epithelial healing. These results indicate that particular care should be taken to minimize corneal contact with MMC in the clinical setting, particularly when epithelial defects are present.


Acquired heterochromia with horner syndrome in two adults.

Heterochromia iridis, asymmetry of iris pigmentation, has been well described with congenital Horner syndrome. Acquired heterochromia associated with lesions in the ocular sympathetic pathways in adulthood, however, is rare. Two cases are reported in which sympathectomy in adults resulted in ipsilateral Horner syndrome with heterochromia. In each case, pharmacologic testing with cocaine and hydroxyamphetamine was performed. In both cases, sympathectomy occurred at the level of the second order neuron, but hydroxyamphetamine testing suggested at least partial third order neuron involvement. Acquired heterochromia can occur in adults. The partial response to hydroxyamphetamine in the two cases presented may reflect trans-synaptic degeneration of the postganglionic neuron. A reduction in trophic influences on iris melanocytes may have contributed to the observed heterochromia.


High incidence of sympathetic ophthalmia after contact and noncontact neodymium:YAG cyclotherapy.

Two cases of sympathetic ophthalmia occurring after noncontact neodymium:YAG (Nd:YAG) cyclotherapy have previously been reported. In each case, the patient had undergone filtering surgery in the exciting eye. Although in each case Nd:YAG cyclotherapy was the last surgery performed, the inciting event of sympathetic ophthalmia was unclear. The authors studied three additional patients who developed sympathetic ophthalmia after Nd:YAG cyclotherapy for glaucoma. Two patients developed sympathetic ophthalmia 4 months after noncontact Nd:YAG cyclotherapy, and 1 patient developed sympathetic ophthalmia 18 months after contact Nd:YAG cyclotherapy. All patients had previous cataract extractions but no filtering surgery in the exciting eye. Clinical features included chronic iridocyclitis, choroidal folds, Dalen-Fuchs nodules, and optic disc edema. Combining these cases with the two previously reported cases, the incidence of sympathetic ophthalmia at our institution thus far is 5.8% (4 of 69) and 0.67% (1 of 150) after noncontact and contact Nd:YAG cyclotherapy, respectively. The incidence of sympathetic ophthalmia after Nd:YAG cyclotherapy is high compared with other ocular procedures. The clinician should vigilantly monitor patients after Nd:YAG cyclotherapy and report additional cases that may have occurred at other institutions.


Ophthalmic laser microendoscope ciliary process ablation in the management of neovascular glaucoma.

To evaluate the potential efficacy of ophthalmic laser microendoscope photocoagulation of the ciliary processes in the management of intractable neovascular glaucoma. Ten patients with intractable neovascular glaucoma underwent ophthalmic laser microendoscope ciliary process ablation via a pars plana incision. The device and surgical technique are discussed. Preoperative intraocular pressure (IOP) ranged from 36 mmHg to 62 mmHg (mean, 43.6 mmHg). Postoperative final IOP ranged from 3 mmHg to 27 mmHg (mean, 15.3 mmHg). This represents an absolute decrease of 28.3 mmHg (65%). Postoperatively, 9 eyes had an IOP of less than 21 mmHg, although 3 of these eyes required medication. One eye attained a final IOP of 27 mmHg. All eyes were treated once. Nine patients were treated with carbonic anhydrase inhibitors preoperatively, and six patients were able to discontinue this medication postoperatively. Phthisis was not observed, but hypotony evolved in two eyes with chronic retinal detachment. Follow-up ranged from 6 to 11 months (mean, 8.8 months). This new therapeutic modality, which combines endoscopic visualization of the ciliary processes with diode laser photocoagulation, can be effective in the management of intractable neovascular glaucoma.


Ophthalmic laser microendoscope endophotocoagulation.

The purpose of this article is to describe the function of the ophthalmic laser microendoscope as it pertains to endophotocoagulation in the management of vitreoretinal disease. Fifty-four consecutive vitrectomies with endophotocoagulation were performed using the ophthalmic laser microendoscope instead of endoillumination and endophotocoagulation probes. Intraoperative and postoperative efficacy and complications were evaluated. The ophthalmic laser microendoscope was used to illuminate and view the retina and to deliver diode laser energy in the management of posterior retinal breaks, proliferative retinopathies, and proliferative vitreoretinopathy. The technique of endophotocoagulation was similar to that used routinely in vitreoretinal surgery. The photocoagulation lesions that were created were identical to those delivered by standard endophotocoagulation probes. Intraoperative complications were few, consisting of transient mild retinal or choroidal hemorrhages. Severe postoperative complications related to endophotocoagulation or to use of the ophthalmic laser microendoscope were not observed. The ophthalmic laser microendoscope appears to be a safe and effective method of delivering diode laser energy to the retina while simultaneously providing illumination, video recording, and a clear endoscopic view despite anterior segment conditions that might otherwise preclude adequate visualization and treatment. Fewer instrument insertions/removals were required for endophotocoagulation. Post-treatment search for peripheral iatrogenic retinal breaks was accomplished by endoscopy.


Purtscher's-like retinopathy in chronic renal failure.

The authors describe the clinical findings of three young women with the previously unreported association of Purtscher's-like retinopathy and chronic renal failure. The authors reviewed the clinical records of three women with chronic renal failure who had been seen at the Oregon Health Sciences University with acute, profound visual loss associated with a severe vaso-occlusive Purtscher's-like retinopathy. Two of the three patients previously had renal transplants, and both were experiencing allograft rejection. One of these two patients was undergoing hemodialysis. The retinopathy was bilateral in two patients, and unilateral in the third. Each of the 5 affected eyes had severe initial loss of vision to less than 20/400, and only one of these eyes had significant visual recovery. None of the patients had recent trauma, pancreatitis, autoimmune disease, or other condition known to be associated with Purtscher's-like retinopathy. A retinal vaso-occlusive disorder resembling Purtscher's retinopathy can occur in patients with chronic renal failure, even in the absence of trauma, pancreatitis, or known autoimmune disease. While the precipitating factor(s) remains unclear, it appears that the retinopathy in this setting may be more severe and associated with a poorer visual prognosis.


Functional blindness and visual impairment in older adults from three communities.

The purpose of this study is to examine the association of sociodemographic factors with functional blindness and visual impairment in an aged population. Three population-based cohorts (East Boston, MA; New Haven, CT; and Iowa and Washington Counties, IA) of persons aged 71 years and older were screened for bilateral functional near and distant vision during an in-home interview in 1988. Screening was completed by 5335 participants. The prevalence of functional blindness increased with age, from 1% at age 71 to 74 years to 17% in those 90 years of age and older. Functional visual impairment increased from 7% at age 71 to 74 years to 39% in those 90 years of age and older. In multivariate analyses, residence in a nursing home, older age, glaucoma, insulin-requiring diabetes at baseline, East Boston site, history of cataract, and lower 1982 income were independent and significantly associated with both functional blindness and visual impairment. Age and nursing home residence were significantly (P < 0.05) more strongly associated with blindness (odds ratios 4.8 and 6.1, respectively) than they were with visual impairment. Functional blindness and visual impairment are quite prevalent among the oldest old and the institutionalized. The number of affected individuals will increase as the population ages and life expectancy increases. Although visual problems are associated with aging, nursing home residence, health problems, and socioeconomic conditions, they may be readily remediable and may lead to immediate improvements in quality of life.


[Development of the immune system].

The development of immune defense mechanisms begins early during fetal life but is not yet completed at birth. The earliest hematopoietic stem cells, which give rise to the lymphocytic and myelomonocytic cell lines, appear between the fourth and eight weeks postconception. T cells, responsible for cellular immune defense mechanisms, are first detectable at 12 weeks and seem to acquire their functional capabilities at the 16th week. B lymphocytes, responsible for humoral immunity, can be identified in the fetal liver at eight weeks and are functional at the 12-th-13th week, with the ability to produce specific IgM antibodies. Thus, in theory, fetuses of more than 16 weeks can produce a full immune response. Neonates still have incomplete development of a number of mechanisms involved in nonspecific immunity (natural killer, polynuclear and macrophage chemo-attraction, complement system).


[Ovum sampling techniques for prenatal diagnosis of viral infections].

Two techniques can be used to achieve antenatal diagnosis of viral infections, i.e., amniocentesis and cord blood sampling. these procedures and their risks to the fetus are described in this article. Amniocentesis can be performed at the 15th week after the last menstrual period (LMP) under ultrasonographic guidance and carries a risk of fetal death of approximately 0.5%. Cord blood sampling, more difficult technically, can be performed at the 18th week after the LMP but is not useful for the antenatal diagnosis of infectious diseases before the 22nd or 23rd weeks. Fetal death rate is 0.5 to 1% when the procedure is performed by experienced operators. Other sampling methods, including fetal sampling and chorionic villus sampling can be used only in specific clinical situations. Situations in which ovum sampling is appropriate are outlined according to the circumstances of discovery of viral infections and the general problems raised. Emphasis is put on the need to use detailed protocols to perform these sampling procedures in order to minimize fetal risks and effectively exploit collected data.


The simian immunodeficiency virus infected macaque: a model for pediatric AIDS.

Maternal-to-infant transmission of simian immunodeficiency virus (SIV) has been demonstrated in the rhesus macaque following experimental infection of pregnant rhesus monkeys, either parenterally or by inoculation of virus into the amniotic fluid. Virus infection occurred in 3 of 12 (25%) rhesus infants born to mothers with SIV infection induced by parenteral inoculation of virus during gestation. However, these infants did not become seropositive or virus positive until they were 9-15 months old, suggesting that virus infection most likely occurred as the result of breast feeding. Infection has also been demonstrated in one rhesus infant following virus inoculation into the amniotic fluid during late gestation. These observations support the increasing evidence that intrapartum or postpartum infection may be important mechanisms for the maternal-infant transmission of HIV. The SIV-infected macaque should prove to be a useful model to evaluate the timing and mechanisms of lentivirus infection in infants, to determine maternal factors associated with transmission to the fetus or infant, and to evaluate therapeutic regimens for the prevention or treatment of pediatric AIDS.


Rubella and pregnancy.

Maternal rubella infection during pregnancy can induce more or less severe congenital defects. In France in 1989, 43 rubella infections in pregnant women were recorded by the National Laboratory of Health. Diagnosis of primary rubella infection rests on detection of specific IgM antibodies. The most reliable technique for detection of IgM antibody is the antibody-capture immunoassay. Presence of rubella-specific IgM antibodies must be interpreted with caution: specific IgM antibodies may occur following reinfection and there have also been reports of rubella-specific reactivity in sera collected after infections with other viruses. In some cases, presence of rubella-specific IgM antibodies cannot be ascribed to any of the reasons above and remains completely unexplained. Fetal infection can be demonstrated by detecting rubella-specific IgM antibodies in fetal blood. However, very sensitive techniques must be used in order to obtain reliable results. Today, widespread immunization is still essential. Immunization of all seronegative pregnant women immediately after delivery is especially important since most mothers of babies with congenital rubella were multiparous. Women exposed to rubella may be offered normal human immunoglobulins as soon as possible after the exposure; if delayed, this treatment may be ineffective.


[Fetal erythropoiesis and parvovirus B19].

Target cells for the human parvovirus B19 include erythroid progenitors located in the bone marrow in adults and in the liver in fetuses of 12 to 30 weeks gestational age. The main manifestations of fetal parvovirus B19 infection seem to be related to lysis of the erythroid progenitors which causes non immune hydrops fetalis with severe anemia, congestive heart failure, generalized edema and death. The exact incidence of human parvovirus B19 infection during pregnancy remains unclear.


[Vertical transmission of HTLV-I].

Vertical transmission of the human T-cell leukemia type 1 (HTLV-1) from seropositive mothers to their offspring has been extensively studied. Transmission occurs mainly through breastfeeding. Prevention relies on screening pregnant women (and wet-nurses) for HTLV-1 antibodies and advising seropositive women to refrain breast feeding. Recently, antigen detection or genome detection (using PCR) studies on lymphocytes from neonates born to HTLV-1 positive mothers have established that prenatal vertical transmission does occur, although in only a small proportion of cases (0.5 to 7%). Studies on the HTLV-1 and improved understanding of its modes of transmission may provide new insight into the transmission of the HIV.


[Virologic diagnosis of HIV infection in children].

The rate of mother-to-infant transmission of the HIV approximates 20%. Early treatment and monitoring of infected infants are feasible only if diagnosis is established promptly. Diagnosis at birth relies on techniques that demonstrate presence of the virus (viral cultures, Polymerase Chain Reaction (PCR) antigenemia). However, beyond six months of age, detection of evidence of an immune response to the virus can also be used (anti-HIV IgA, in vitro production of antibodies: ELISPOT or in vitro antibody production (IVAP). In practice, it should be borne in mind that the sensitivity of each technique varies with age.


[Prevention of fetal and neonatal transmission of the varicella-zoster virus].

Varicella occurs in 0.7 to 0.13% of pregnant women. The risk of transmission of the varicella-zoster virus to the fetus is small. The virus causes malformations (cutaneous scars and above all central nervous system anomalies). Mother-to-offspring transmission is more common during the perinatal period (20%), when mild or severe (fatal in 20% of cases) congenital varicella may occur. Prevention of transmission of the varicella-zoster virus from the mother to her fetus or neonate rests on detection of fetal varicella (antenatal ultrasonography, fetal IgM assays) and on administration of both specific anti-VZ virus immune globulins and acyclovir to the mother and neonate during the perinatal period.


[Effect of acute blood loss on catecholamine balance in the pulmonary circulation in anesthetized rats].

The contribution of pulmonary inactivation of catecholamines (CA) in the formation of their level in circulating blood during the development of a posthemorrhagic reaction was studied. Pulmonary CA inactivation was evaluated according to the arteriovenous difference (right ventricle and carotid artery) in epinephrine (E) and norepinephrine (NE) whose concentration was determined by the method of highly-effective liquid chromatography with electrochemical detection. Reciprocal phase changes in the dynamics of the arteriovenous difference in NE and E and levels of the corresponding CA in arterial blood plasma were discovered during the development of the posthemorrhagic reaction. Pulmonary inactivation of CA increased by the 2nd minute, then dropped below the initial level with subsequent restoration. The NE level in the arterial blood plasma was marked by a strictly contrary dynamics, while the concentration of E reached maximum when inactivation of E in the lungs was minimal (5th minute). The mechanisms and physiological significance of the discovered phenomenon are discussed.


[Blood granulocyte priming in inflammation].

Metabolic activity of peripheral blood granulocytes during the development of inflammatory processes in animals (rats) was studied by chemiluminescence (CL) with luminol. Intensification of the CL- response of granulocytes during an acute inflammatory process induced by intravenous or intraperitoneal zymosan injection reflected the development of mononuclear infiltrative processes. No changes occurred in CL of circulating granulocytes in oxidative injury to the lungs of rats breathing pure oxygen, which was attended by increased infiltration of polynuclear cells.


[Prooxidant effect of inflammation mediators].

The authors studied the effect of inflammation mediators--serotonin, histamine, bradykinin, as well as that of trypsin on lipid peroxidation (LPO). It was demonstrated by chemiluminescence of native hepatic mitochondria in vitro and blood serum in vivo and tests for diene conjugates and malonic dialdehyde that inflammation mediators (histamine, serotonin, bradykinin) and the proteolytic enzyme trypsin activate LPO processes, which correlates with the antiinflammatory effect of these biologically active substances.


[Comparative evaluation of the wound-healing effect of benzofuracaine, etaden, and xanthinol nicotinate in an experiment].

The effect of benzofuracaine, etaden, and xanthinol nicotinate on the healing of skin wounds was studied in rat experiments. On days 1-14 of postmechanical injury, intramuscular benzofuracaine (15, 30, 60, and 120 mg/kg), etaden (20 mg/kg), and xanthinol nicotinate (each drug alone) reparative processes in the skin wounds developed more rapidly and processes of microcirculation in the region of the injury were normalized. The wound-healing effect of benzofurocaine in an ortimal dose of 60 mg/kg was more marked than that op etaden and xanthinol nicotinate. With benzofuracaine and etaden, the skin wounds healed completely by the 14th day of the experiment in 57% and 28.6% of animals, respectively. Such cases were not encountered among animals treated with xanthinol nicotinate and in the controls (untreated animals).


[Atmospheric electromagnetic field oscillations and the nature of the proliferative process in the focus of acute inflammation].

Experiments were conducted on 300 rats kept in a warm room (16-18 degrees C) in the cold season of a year to study the influence of a signal effect of atmospheric processes, namely changes in of atmospheric electricity parameters, on the early proliferative reactions in a focus of acute inflammation. The results of 50 experiments on which a geomagnetic storm was superimposed were excluded form the analysis subsequently. Inflammation was modelled by implanting a 3 x 4-mm piece of a cover glass under the skin. Following 48 hours the number of hematogenic and histiogenic cells superimposed on one surface of the implanted glass was counted. These were fibroblasts, macrophages, polynuclear and giant cells. An analysis showed that frosty weather, the existence and direction of a wind, atmospheric-electrical processes preceding the passage of meteorological fronts influenced the nature of proliferative responses. The authors revealed the efficacy of electromagnetic screening of the animals, which mitigated the effect of the atmospheric electromagnetic waves.


[Effect of the fever reaction on lymph cytologic composition and lymph node structure].

The authors studied the cytologic composition of afferent and efferent lymph and the morphology of the popliteal lymph node during a fever reaction of various duration. The fever reaction was attended by quantitative and qualitative in the cytologic composition of both lymph types. Reduction of the leukocyte count in the first hours of fever was replaced by its increase: the percentage of small- and moderate-size lymphocytes reduced, while that of poorly-differentiated cells--blasts and prolymphocytes--increased. The number of neutrophils and monocytes in the afferent lymph grew and its toxicity increased. Phenomena of dynamic stereotypy were noted during the development of the fever reaction: hyperplasia of the lymphatic substance with an increase of the number of lymphocytes and poorly-differentiated cells in the follicles and paracortical zone of the lymph nodes, hyperplasia of the pulpar bands, and signs of a macrophageal reaction.


[Lymphopoiesis in mice with alloxan diabetes in experimental insulin therapy].

The authors studied the proliferative response of central and peripheral lymphoid organs of male BALB/c mice with alloxan diabetes to injections of a zinc-insulin suspension (1 u/mouse/24 hours) given for 1, 3, or 5 days. Insulin therapy failed to compensate the diabetes completely, but normalized to a considerable measure the diminished proliferative activity of the young lymphoid cells of the thymus and bone marrow from the third day of the experiment. Autoradiographic study showed that the thymus of diabetic mice was marked by a significant reduction of the percentage of young lymphoid cells bearing insulin receptors on their surface. The results of the experiments point to insulin dependence of central lymphopoiesis in rats.


[Erythrocyte membranes and antioxidant provision in experimental acute pancreatitis].

Experiments were conducted on rats with induced edematous and hemorrhagic forms of acute pancreatitis (AP) to study the parameters characterizing the state of the red cell membranes: hemolytic efficiency, glucose-6-phosphate dehydrogenase activity, extra-erythrocytic hemoglobin concentrations. The values characterizing the bio-antioxidative defense were also studied: superoxide dismutase activity and antioxidative property. The development of experimental AP is attended by injury to the red cell membranes among the causes of which is poor antioxidative provision.


[Zinc content in pancreatic islets in experimental diabetes induced by chelating agents].

The zinc content in microresected islets of rabbits, mice, rats, and guinea pigs was determined by atom-absorption spectrophotometry. The content was found to be highest in rabbits, and diabetes was induced in them by chelating agents easily. Injection of dithizone or 8-(p-toluenesulfonylamine) quinoline failed to induce diabetes mellitus in mice, rats, and guinea pigs. It is concluded that diabetogenic chelating agents are capable of producing irreversible diabetogenic affection in those beta-cells which contain a critical concentration of reactant zinc.


[Content of trace elements and steroid hormones in blood and tissues of internal organs of rats during an inflammatory process in the bronchi].

Prolonged interrupted inhalation of nitrogen dioxide in a dose of 36.0 +/- 2.2 mg/m3 was attended by definite morphological signs of inflammation in the lungs of rats (hyperplasia of goblet cells, thickening of the basilar membrane, differentiation of ciliated epithelium, etc.), reduction of the zinc content in all studied tissues and testosterone levels in blood. Intramuscular injection of 1% testosterone propionate normalized the blood level of the hormone and influenced the synthetic processes in the cells of the bronchial epithelium and the rate of its regeneration. To raise the efficacy of the correction of the pathological process in the lungs it is suggested that hormonal therapy should be combined with correction of zinc deficiency in the organism.


[Functional possibilities of pancreatic insular apparatus under prolonged conflict situation and use of thyroliberin in glucose].

Under conditions of a prolonged emotional stress, disturbed regulation of blood sugar level was encountered along with a reduction of the thymus mass in 85.7 of animals. Diminution of the adaptational properties of the organism in such conditions is revealed during a sugar load. Preventive administration of thyroid-releasing hormone in the studied stress reaction makes it possible to maintain the compensatory reserves against the glucose load test.


[Preclinical evaluation of the therapeutic efficacy of L-dopa in chronic gastric ulcer].

The authors studied the peculiarities of the course taken by experimental gastric ulcer in rabbits under the effect of the norepinephrine precursor 1-dioxyphenylalanine (L-DOPA) injected parenterally in a dose of 10 mg/kg twice a day for 14 days. As compared to the controls (nontreated ulcer), L-DOPA restored significantly more rapidly the bioenergetic processes in the gastric mucosa which were disturbed as the result of ulcerogenesis, provided for stimulation of reparative regeneration, and reduced the terms of ulcer cicatrization.


[Hormonal mechanisms of pathogenesis and cure of experimental gastroduodenal ulcer by the Okabe technique].

The dynamics of hormonal secretion was studied in relation with the development of an ulcer defect in rats with acetate-induced gastroduodenal ulcer after Okabe. The formation of the ulcer was accompanied by increased gastrin, glucagon, cortisol, growth hormone, and histamine secretion and reduced glucose tolerance. The level of intragastric pH reduced, the activity of proteolytic enzymes in the gastrointestinal tract increased. Correlation analysis bore evidence for the contribution of gastroenteropancreatic hormones to the compensatory-adaptational responses, whereas with a higher blood cortisol level the surface of the ulcer defect was larger. Oral mineral water (Essentuki No. 17) promoted the secretion of gastrin, glucagon, and insulin and the experimental ulcers grew smaller in this case. The involvement of the hormonal factors in the mechanisms of the development of experimental acetate-induced ulcer is discussed.


[Regulatory role of duodenal evacuation activity in determination of the absorption rate of organic components of duodenal chyme].

The effect of inhibited duodenal motor-evacuation on the rate of protein, glucose, and lipid absorption was studied in chronic experiments in 5 polyfistulous dogs. Evacuation was inhibited by division of Treitz's ligament (a model of duodenostasis). The results of the experiments are evidence of a considerable regulatory effect of chyme evacuation rate on the value of the flow of substances from the enteral medium into the blood. The evacuation rate is in inverse proportion to the adsorption rate.


[Analysis of the mechanism of the ulcerostatic effect of tris-[2-hydroxyethyl] ammonium salt of iron-containing polyacrylic acid].

It was demonstrated in experiments on rats with acetate gastric ulcer that ammonium salt tris-(2-hydroxyethyl) of iron-containing polyacrylic acid intensifies the development of granulation-fibrous tissue and promotes fuller restoration of connective-tissue polymers--collagen, noncollagenous proteins, and glycosaminoglycans in it. The biochemical results are confirmed by histological studies.


[Decrease in bacterial toxemia after radiation-thermal injury in the restoration of motor-evacuation function of the gastrointestinal tract].

Experiments were conducted on male Wistar rats to study the possibility of restoration of the motor-evacuative function (MEF) of the gastrointestinal tract (GIT) after radiothermal injury (irradiation with a dose of 6 Gr+Stage IIIb burn). Changes in the development of bacterial intoxication in the injured organism were analysed. Restoration of GIT MEF in the injured rats leads to simultaneous diminution of the degree of bacterial toxemia which plays an important role in the pathogenesis of radiothermic injury.


[Change in various properties of catalase in the small intestine of rats after vagotomy].

To evaluate the antioxidative system of the small intestine in disturbed parasympathetic innervation, the authors studied the activity of catalase, its resistance to substrate inactivation (catalytic capacity) and reduction potential (reduction of Fe3+ to Fe2+) in the enteric homogenate in different periods (on day 14 and 30) after bilateral subdiaphragmatic truncal vagotomy. Vagotomy did not change catalase activity but was attended by an increase of catalase catalytic capacity and reduction potential. It is suggested that the discovered changes of the studied parameters are manifestations of responses of the antioxidative protective system of the small intestine to the activation of lipid peroxidation.


The resurgence of acute rheumatic fever in the United States.

Several areas in the United States have experienced significant outbreaks of acute rheumatic fever. Reasons for the reappearance of acute rheumatic fever are incompletely understood but may relate to changes in the organism. Fortunately, however, GABHS has remained exquisitely susceptible to penicillin. Given the resurgence in cases of acute rheumatic fever, the practicing physician needs to be vigilant in diagnosing and ensuring adequate treatment of acute streptococcal pharyngitis. In addition, acute rheumatic fever must be considered in a patient who presents with a new onset murmur, a migratory polyarthritis, chorea, or a rash suggestive of erythema marginatum.


[Effect of peptides of the tracheal mucosa and vascular wall in acute hyperoxic lung injury].

It was demonstrated that peptides of the tracheal mucosa (PTM) and peptides of the vascular wall (PVW) produce a certain protective effect in hyperoxic lung injury. The peptides, (PTM to a greater measure) prolonged the survival of mice and inhibited the dynamics of the growth of the lung coefficient in rats. PTM reduced the formation of malonic dialdehyde and increased the activity of glucose-6-phosphate dehydrogenase in the lungs. Morphometric studies showed that PTM produce a more marked inhibiting effect on exudation in to the alveoli; besides, the administration of PTM contributed greatly to maintenance of the empty space and "total volume" of the alveoli.


An international comparison of the prevalence of streptococcal infections and rheumatic fever in children.

Differences in the socioeconomic standards of living remain an important and feasible partial explanation for the difference in incidence of rheumatic fever following GABHS infection in Egyptian compared with American children. However, past and ongoing studies of the epidemiology, diagnosis, and treatment of GABHS infections in Egypt, the United States, and elsewhere suggest other significant factors are relevant. Additional knowledge about the rheumatogenic GABHS serotypes that are most prevalent in all countries is an important area where additional research is needed. Streptococcal research will help not only in improving the quality of primary prevention of rheumatic fever, but also in developing streptococcal vaccines.


Chronic graft-versus-host disease and pulmonary function.

Pulmonary complications are a major cause of morbidity and mortality in bone marrow transplant recipients. Earlier series, consisting mainly of adults, have shown evidence of obstructive changes of pulmonary functions in association with chronic graft-versus-host disease (CGVHD). We longitudinally evaluated spirometry in 46 patients who received bone marrow transplants as children or as young adults to determine whether they had similar abnormalities. Group mean FEV1/FVC, and percent predicted FVC, FEV1, and FEF25-75 values did not demonstrate obstructive changes in association with CGVHD in this patient population. Our findings suggest that younger patients with CGVHD, as a group, may fare better than older bone marrow transplant recipients with CGVHD. However, due to small sample sizes, it cannot be conclusively stated that the pulmonary function parameters analyzed do not differ in the two patient groups.


A scoring system for lung function tests in infants.

Measurements of thoracic gas volume (TGV), airway resistance (Raw), and airway conductance (Gaw) were calculated in a group of 42 normal infants using a whole-body plethysmograph. Maximum expiratory flow at functional residual capacity was measured in a separate group of 108 normal infants. Using data obtained from these infants the following regression equations were calculated: Gaw (L.s-1.cmH2O) = -0.0475 + 0.00164 x length (cm) square root of TGV (mL1/2) = -3.22 + 0.263 x length (cm) VmaxFRC (mL.s-1) = -173 + 5.2 x length (cm). The standard errors of prediction are a measure of the scatter of individual results from the normal population about the true regression line. They were used to define limits of the normal ranges for these tests of lung function, and to develop a scoring system. This approach is preferable to expressing results as percent predicted, which gives no indication of how likely a measurement is to be within normal limits.


Reproducibility of late phase pulmonary response to exercise and its relationship to bronchial hyperreactivity in children with chronic asthma.

To determine the reproducibility of the delayed response to exercise and its effect on bronchial hyperreactivity, we had 26 asthmatic children perform treadmill exercise challenge on two occasions 1 week apart. Both challenges were preceded by 2 control days and 1 histamine challenge day, and were followed by another histamine challenge day. Peak expiratory flow rate (PEFR) was measured hourly for 12 hours on each control day and for 12 hours after each exercise or histamine challenge. During the first week, five patients showed a late reaction (PEFR change > 15%) after exercise, which was present in only two of them the following week. These two patients, however, also showed a spontaneous fall > 15% of PEFR from baseline during the other control study days. A similar pattern was seen in two other patients who had a late response during the second exercise challenge but not during the first. No significant change occurred in histamine PC-20 FEV1 between before and after the exercise challenges. An apparent late asthmatic response after exercise challenge may represent a within-day fluctuation in pulmonary mechanics that develops spontaneously in children with asthma.


The clinical and imaging spectrum of findings in patients with congenital lobar emphysema.

Congenital lobar emphysema (CLE) is an important cause of infantile respiratory distress that may require surgical intervention. We retrospectively reviewed the clinical and imaging findings in eight infants with CLE. In our series, CLE was more common in females, predominantly involved the right lung, often presented with an opaque lobe from retained fetal lung fluid, and frequently involved the lower lobes, multiple segments or lobes, and both lungs. Most patients with CLE were diagnosed and managed on the basis of clinical and plain radiographic findings alone. Computed tomography, and occasionally ventilation/perfusion scintigraphy, were helpful in confirming the diagnosis and in guiding management decisions in several cases; bronchoscopy showed that stenosis of the right mainstem bronchus was the cause of CLE in one case. Three patients experienced progressive worsening of respiratory distress and required surgical resection of the affected lobe for cure; the remaining five patients were managed medically with eventual remission of symptoms.


Evaluation of the Oxford and Sheffield SIDS risk prediction scores.

To evaluate the clinical usefulness (sensitivity and specificity) of the Oxford and Sheffield birth scores for prospective identification of infants at high risk of SIDS. Retrospective medical record reviews of prospectively identified, autopsy-validated SIDS and living control infants. Consecutive sample of 140 infants, born between 1/1/83 and 12/31/87, who died suddenly and unexpectedly in the Avon Area Health Authority in southwest England between 1/1/84 and 12/31/88. Seventeen of the cases were excluded: 6 because they lacked adequate clinical records, 11 because they were not SIDS. The 637 control infants were comprised of every 80th delivery between 1/1/83 and 12/31/87 in the three major hospitals in the area. SIDS incidence was 2.85/1,000 live births. Using standard cut scores to define high SIDS risk (2.0 for Oxford and 500 for Sheffield), sensitivities were 0.55 and 0.35 and specificities were 0.78 and 0.89 for the Oxford and Sheffield scores, respectively. SIDS risk for infants in the high risk group was 7.3/1,000 (Oxford) and 9.3/1,000 (Sheffield). Since there is no intervention with proven efficacy for SIDS prevention, and since approximately one half of SIDS cases occur in low risk groups, clinical use of these scoring systems for allocation of health care resources or personnel for the sole purpose of SIDS prevention is not justified.


Steroid resistance in asthma: our current understanding.

While much information has recently been obtained regarding the features of steroid-resistant asthma, it continues to be a dilemma for practitioners, and investigation into its mechanisms will remain an important part of asthma research. Until a clear marker defining steroid-resistant asthmatics is found, the principle first put forth by Carmichael and colleagues should be adhered to: that is, asthmatics resistant to glucocorticoid therapy need to be identified at an early stage so that unnecessary and perhaps harmful therapy can be discontinued. A 10 day course of high-dose (> or = 30 mg/day) systemic glucocorticoid therapy, as suggested by Kamada and colleagues, may constitute an adequate trial and may sufficiently identify asthmatics who may require alternative treatments. A more rational approach to the selection of alternative asthma treatments will be gained when the mechanisms of steroid resistance are identified.


Validation of respiratory inductance plethysmography ("Respitrace") for the measurement of tidal breathing parameters in newborns.

The ratio of the time to reach peak (maximum) tidal expiratory flow (Tme) to total expiratory time (Te) is smaller in infants who later develop lower respiratory tract disease. In previous studies infants have been sedated and flow measured using a pneumotachograph with face-mask. These methodological factors are known to affect tidal breathing, and the frequent need for sedation limits the use of the technique to relatively small studies. The aim of this study was to validate uncalibrated respiratory inductance plethysmography (Respitrace) to measure Tme/Te in unsedated newborns. Nineteen normal term infants were studied during quiet sleep. Agreement between Tme/Te measured directly using a pneumotachograph and with Respitrace was assessed in 15 infants. Repeatability of the Respitrace technique was assessed in 10 infants. The mean Tme/Te for the 19 infants using Respitrace was 0.46 (S.D. 0.14). The mean difference between Tme/Te obtained using Respitrace and that measured with a pneumotachograph was 0.014; 95% of Respitrace readings were between -0.042 and 0.070 of the pneumotachograph values. The mean difference between repeat Respitrace values was 0.02 with 95% of the second measurements within 0.066 of the first. These results indicate that Respitrace can be used to determine Tme/Te accurately.


Facemasks versus mouthpieces for aerosol treatment of asthmatic children.

Mouthpieces and facemasks are being used with nebulizers for delivery of medication in acute asthma. To compare the effectivity of the two devices, 64 children age 6 to 19 years presenting to the hospital with acute asthma were enrolled in a randomized, single-blind study. Group 1 used a facemask. Group 2 used a mouthpiece connected to the nebulizer via short T-shaped tubing. Clinical evaluation and spirometry were performed at baseline and 20, 40, and 60 minutes after a single treatment with albuterol. Forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1), and forced expiratory flow over the middle 50% of FVC (FEF25-75) were determined at each point. Adverse effects were recorded. There was no significant difference in improvement between the groups. Patients with nasal congestion, age below 10 years, or severe airway obstruction did equally well with each method. Patients in the facemask group had a higher incidence of tremor. We conclude that the mouthpiece is an effective as the facemask and produces less tremor.


Changes in plasma FcRIII demonstrate increasing receptor production during late pregnancy and after preterm birth.

We have previously described reduced expression of the Fc gamma receptor type III on the cell membrane (M-FcRIII) of neutrophils from very preterm neonates. To investigate the mechanism underlying this reduced receptor expression, we have measured neutrophil-derived soluble FcRIII (S-FcRIII) in the plasma of fetuses and neonates from 19 wk gestation. S-FcRIII in fetal plasma and in preterm neonates born before 32 wk gestation was consistently low [mean 13.6 +/- 1.2% (mean adult S-FcRIII = 100%, range 30-240%)]. In utero, S-FcRIII starts to rise from 33 wk and increases more than 4-fold to reach adult levels by term. S-FcRIII measured sequentially in preterm infants born as early as 24 wk of gestation showed a rapid postnatal increase to reach adult levels within 3 wk of birth. The changes in S-FcRIII paralleled changes in M-FcRIII expression on the cell surface. These observations point to a reduced rate of FcRIII production by fetal neutrophils as opposed to an increase in receptor release. The parallel increase in S-FcRIII and M-FcRIII suggests that there may be a programmed activation of FcRIII synthesis within individual cells late in the 3rd trimester of fetal development. In addition, FcRIII production may be switched on early by preterm birth.


Comparative actin polymerization in neonatal and adult bovine neutrophils in vitro.

Neutrophils rely on active reorganization of the cytoskeleton during movement, and functional deficiencies in the cytoskeletal elements may result in impaired neutrophil-mediated host defense. We have compared and quantitated actin polymerization in neonatal (< or = 48 h old) and adult bovine peripheral-blood polymorphonuclear leukocytes (PMN) using fluorescence flow cytometry. Baseline filamentous actin (F-actin) content of neonatal and adult PMN at time zero differed slightly but were not statistically different (p > 0.05). F-actin content of recombinant human C5a (10(-7) M)-stimulated neonatal PMN increased rapidly within 10 s of stimulation to 59.0% over baseline, then declined. F-actin in adult recombinant human C5a-stimulated PMN continued to increase for 30 s and was elevated 87.3% over baseline before subsequently declining. When stimulated with zymosan-activated bovine serum (10%), neonatal (120.7% increase) and adult PMN (115.1% increase) had similar profiles with no significant differences, and both groups reached peak F-actin levels at 30 s after stimulation. Neonatal PMN stimulated with platelet-activating factor (10(-6) M) attained peak F-actin values at 10 s (72.0% increase over baseline), but actin rapidly depolymerized by 30 s poststimulation (reduced to 29.0% increase). Adult PMN stimulated by platelet-activating factor also attained peak values by 10 s (97.6% increase over baseline), but in contrast to neonatal PMN the F-actin remained elevated at 30 s in the adult PMN (still increased 79.5%; p < 0.0.5 compared to neonatal F-actin).(ABSTRACT TRUNCATED AT 250 WORDS)


Sleep organization and energy expenditure of breast-fed and formula-fed infants.

Sleep organization of infants may be influenced by differences in nutrient intakes from human milk and formula. Because sleep/awake and sleep stage patterns affect energy expenditure, we hypothesized that differences in sleep organization between breast-fed and formula-fed infants might account in part for differences in energy expenditure between feeding groups. Sleep stages and cycling of 4-mo-old breast-fed (n = 10) formula-fed (n = 10) infants were studied with simultaneous measurements of energy expenditure. EEG, electrooculogram, body movement by triaxial accelerometry, heart rate, and oxygen saturation were monitored during an overnight sleep session. Sleep stages, nonrapid eye movement (NREM), and rapid eye movement (REM) were determined. Behavioral observations were recorded by video tape and by a technologist. Oxygen consumption and carbon dioxide production were measured with an indirect calorimeter. Total number and duration of sleep cycles, REM latency, number of NREM and REM epochs, and duration of NREM epochs did not differ between feeding groups. Sleep latency was shorter (p < 0.05) and duration of REM epochs longer (p < 0.01) in the formula-fed group. Formula-fed infants spent a higher percentage of sleep time in REM compared with the breast-fed infants (42 versus 34%) (p < 0.003). Conversely, breast-fed infants spent a higher percentage of sleep time in NREM sleep and their heart rates during sleep were lower (114 versus 126 bpm; p < 0.01). Energy expenditure during REM sleep was 13.0 +/- 4.4% higher than during NREM sleep (p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)


Pain perception and effectiveness of the eutectic mixture of local anesthetics in children undergoing venipuncture.

The emulsion of lidocaine and prilocaine (EMLA) is effective in preventing the pain of venipuncture in children. It is therefore important to identify children who could benefit the most from EMLA. We studied the safety and feasibility of two methods of application of EMLA (patch and cream) in a randomized, open-label trial of EMLA patch versus EMLA cream in 160 children with chronic diseases undergoing venipuncture. EMLA patch or cream was applied 60 to 120 min before puncture. Pain was assessed by the children using a visual analogue score. Children also scored the pain of their last puncture and the pain of removing the tape. EMLA patch and cream had similar efficacy (visual analogue scores for the venipuncture were 8.5 +/- 16 and 9.5 +/- 17 out of 100, respectively). Side effects occurred in similar frequencies in the two groups. Adhesiveness of the patch was less effective than that of the cream with Tegaderm. Age was a major determinant of pain perception; younger children recalled more severe pain in their previous puncture. Children recently diagnosed had higher visual analogue scores than those with a long history of chronic disease. We concluded that EMLA patch and cream have a similar efficacy in children undergoing venipuncture. Young children recently diagnosed with chronic disease are most likely to benefit from EMLA.


Changes in piglet auditory brainstem response amplitudes without increases in serum or cerebrospinal fluid neuron-specific enolase.

We studied the relationship between changes in auditory brainstem responses (ABR) and serum and cerebrospinal fluid levels of neuron-specific enolase (NSE) in hyperbilirubinemic 2- to 8-d-old piglets. Infusion of a stabilized solution of bilirubin resulted in serum bilirubin levels of 571.1 +/- 48.8 mumol/L (mean +/- SEM) after 6 h. ABR were obtained at baseline and then hourly until the piglets were killed. We measured peak amplitudes and latencies for waves I-V, as well as latency for the post-V trough. Changes in amplitudes and latencies were analyzed as slopes because of heterogeneous variances. Over time, a significant reduction was observed in peak II-V amplitudes of bilirubin-infused piglets, but not in those of corresponding controls. No change was observed in latencies. NSE was analyzed by RIA. Serum NSE remained stable throughout the experiment (means 5.1-6.6 micrograms/L) and did not differ between the groups. Cerebrospinal fluid NSE values also remained stable, and no differences that could be ascribed to hyperbilirubinemia were detected. We conclude that hyperbilirubinemia induced significant changes in piglet ABR amplitudes without concomitant evidence of severe neuronal compromise, as might have been indicated by significant increases in serum and/or cerebrospinal fluid NSE levels. This provides further support to the clinical impression that early ABR changes during hyperbilirubinemia may be reversible.


Transient neonatal hypothyroxinemia and the auditory brainstem evoked response.

Ten premature infants with low serum thyroxine levels (less than 84 nmol/L) were compared with 10 biochemically euthyroid infants to determine whether hypothyroxinemia in such infants can lead to alterations in the auditory pathway. The auditory pathway was studied between 6 and 11 wk of life by analyzing brainstem evoked potentials elicited by a 10/s, 75 dB above normal adult hearing level click stimulus presented at the infant's ears. Peak latencies of components I, III, and V and interpeak latencies I-III, III-V, and I-V did not yield statistically significant differences between groups. The present study indicates that untreated neonatal hypothyroxinemia does not lead to abnormalities of auditory brainstem evoked response.


Cerebral hemodynamic effects of treatment with modified natural surfactant investigated by near infrared spectroscopy.

The purpose of this study was to investigate the effects on cerebral hemodynamics of administering modified natural surfactant (Curosurf, 200 mg.kg-1) to infants requiring mechanical ventilation for hyaline membrane disease. Observations were made using near infrared spectroscopy on 20 infants for between 26 and 109 (median 57) min before and 22 to 112 (median 46) min after surfactant instillation. Changes in cerebral oxyhemoglobin concentration and cerebral blood volume (CBV) were monitored continuously; cerebral blood flow, oxygen delivery, and the response of CBV to changes in arterial carbon dioxide tension were measured while the infants were stable shortly before and after surfactant was given. Cerebral oxyhemoglobin concentration fell transiently in all infants immediately after surfactant by a median of -0.21 (range -0.46 to 0.05) mL x 100 g-1, but quickly recovered so that the median change during the 10 min after surfactant was 0.01 (-0.46 to 0.46) mL x 100 g-1. Alterations in CBV also occurred ranging from -0.44 to 0.40 (median 0) mL x 100 g-1, which represented -12 to 16% of total CBV; these changes rapidly resolved. When the infants were stable before and after surfactant, the values for mean (SD) cerebral blood flow were 20.5 (7.5) and 23.1 (5.2) mL.100 g-1 x min-1, respectively (n = 9); for mean cerebral oxygen delivery, values were 2.71 (0.89) and 3.15 (0.73) mL x 100 g-1 x min-1 (n = 9); and for response of CBV to changes in arterial carbon dioxide tension, they were 0.14 (0.09) and 0.11 (0.11) mL x 100 g-1 x kPa-1 (n = 16); these changes were not statistically significant.(ABSTRACT TRUNCATED AT 250 WORDS)


Response of the cerebral circulation to hypocarbia in postasphyxia newborn lambs.

Respiratory alkalosis is used in the treatment of newborn infants with persistent pulmonary hypertension. Many of these infants have suffered a prior asphyxial insult. Previous studies in a newborn lamb postasphyxia model have demonstrated abnormalities in the response of the cerebral circulation to hypoxia and to changes in blood pressure. Although vasodilation in response to these stimuli was impaired, the ability of the brain to extract oxygen was not. Therefore, because the principal response of the cerebral circulation to lowering arterial carbon dioxide tension is vasoconstriction with a compensatory increase in oxygen extraction, it was hypothesized that the postasphyxia response of the cerebral circulation to decreases in carbon dioxide tension would be intact. Ten newborn lambs were subjected to an asphyxial insult. Postasphyxia whole brain and regional blood flows were measured at three to four different levels of arterial carbon dioxide tension using the radiolabeled microsphere technique. In addition, arterial and venous oxygen content and blood gases were measured in the brachiocephalic artery and the sagittal sinus. The response of whole brain cerebral blood flow (CBF) to changes in arterial carbon dioxide tension (PaCO2) is described by ln CBF = 0.031 PaCO2 + 3.15 (r = 0.83, p < 0.001). Responses of individual brain regions did not differ from whole brain flow. Cerebral oxygen consumption remained stable, and fractional O2 extraction (E) increased according to the relationship ln (1 - E) = -0.023 PaCO2 - 1.35 (r = 0.89, p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)


Cerebral oxidative metabolism during hypothermia and circulatory arrest in newborn dogs.

To ascertain the alterations in cerebral oxidative and energy metabolism that occur during hypothermic circulatory arrest, nitrous oxide-anesthetized, paralyzed, and artificially ventilated newborn dogs were surface cooled to 18-20 degrees C, after which their hearts were arrested with KCl. At 10, 30, 60, and 105 min of circulatory arrest, their brains were prepared by in situ freezing for the regional analysis of glycolytic intermediates and high-energy phosphate reserves. Hypothermia alone was associated with optimal preservation of labile metabolites in brain, even in caudal brainstem and cerebellum, compared with barbiturate-anesthetized littermates. After onset of hypothermic circulatory arrest, glucose decreased progressively in cerebral cortex, caudate nucleus, hippocampus, and subcortical white matter to negligible levels by 30 min. Pyruvate increased transiently (+50%) at 10 min, whereas lactate increased and plateaued (10-11 mmol/kg) at 30 min. The disproportionate increases in pyruvate and lactate resulted in a progressive rise in the lactate/pyruvate ratio. Phosphocreatine fell precipitously to < 0.5 mmol/kg in all structures, with a preservation of ATP for the first 10 min of cerebral ischemia. Thereafter, ATP decreased to < 0.1 mmol/kg in cerebral cortex and between 0.1 and 0.2 mmol/kg in caudate nucleus, hippocampus, and white matter. Total adenine nucleotides (ATP+ADP+AMP) were partially depleted by 30 min in the gray matter structures but were unchanged from control for 60 min in white matter. The findings showed a direct correlation between preservation of cerebral energy stores during hypothermic circulatory arrest and the selective resistance of subcortical white matter to ischemic damage.(ABSTRACT TRUNCATED AT 250 WORDS)


Apolipoprotein synthesis in newborn piglet intestinal explants.

To determine the effects of hormones and epidermal growth factor (EGF) on the small intestinal synthesis of apolipoproteins B-48, A-I, and A-IV in the neonatal mammal, apolipoprotein synthesis by proximal jejunal explants from 2-d-old female piglets was studied in tissue culture. Initial comparison studies with various media showed optimal total protein and apo A-I synthesis with Williams' medium E without fetal bovine serum. Sets of explants were prepared containing EGF and various hormones in the medium. After 35S-methionine radiolabeling, explants were homogenized, and specific apolipoprotein synthesis was quantitated by immunoprecipitation as the percentage of total protein synthesis. Apo B-48 synthesis was not affected by any additives except the combination of EGF and hydrocortisone, which slightly decreased synthesis. Apo A-I synthesis was significantly increased by EGF. This EGF-induced increase in apo A-I synthesis was blunted by concomitant treatment with hydrocortisone. In contrast, the combination of insulin and hydrocortisone induced a significant increase in apo A-I synthesis. Although EGF and insulin modestly increased apo A-IV synthesis, the combination of insulin and hydrocortisone treatment up-regulated apo A-IV synthesis by 2.6-fold. Thyroid hormone lacked effect on synthesis of any of the apolipoproteins. EGF, glucocorticoids, and insulin may play regulatory roles in the developmental expression of apolipoprotein synthesis in the neonatal small intestine.


Safety and efficacy of treatment of pediatric cholesteryl ester storage disease with lovastatin.

The aim of this study was to prospectively assess the safety and efficacy of lovastatin in the treatment of cholesteryl ester storage disease in siblings who were ages 11.6 and 5 y at the beginning of treatment. Mean total and LDL cholesterol in the male proband, 7.40 and 5.68 mmol/L, respectively, on diet alone, fell 30% to 5.2 (p < or = 0.001) and 31% to 3.9 mmol/L (p < or = 0.001) on lovastatin 40 mg/d over 3.3 y, with simultaneous resolution of hepatosplenomegaly. In his sister, on lovastatin 20 mg/d for 1.5 y, total and LDL cholesterol fell, but not significantly; her hepatosplenomegaly was also reduced on treatment. Lovastatin was well tolerated without overt side effects or complications and without adverse changes in liver function tests or creatine phosphokinase. Normal and expected accretion of height and weight occurred during the treatment period for both children. Lovastatin appears to be a safe and effective treatment for pediatric cholesteryl ester storage disease.


Prenatal exposure to ethanol in rats: effects on postnatal maturation of the small intestine and liver.

To examine the effects of prenatal exposure to ethanol on postnatal development of small intestinal and liver functions, female rats were accustomed to increasing amounts of ethanol (10 to 25%, vol/vol) in tap water for 1 mo. During pregnancy, ethanol-fed dams had higher daily caloric intake and similar weight gain compared with controls. In ethanol offspring, neonatal mortality was 28.9% compared to 0% in controls. Although ethanol had been withdrawn at birth, pups issued from ethanol-treated mothers showed at 5 and 10 d postpartum decreased values of body weight, jejunal and ileal weights, and intestinal DNA concentration per unit of length, as well as lower specific and total activities in lactase and maltase, compared with controls. DNA synthesis rates, measured by the incorporation of [3H]thymidine into mucosal DNA, were also significantly (-20 to -34%, p < 0.01) depressed in the jejunum and ileum of ethanol pups at 5 and 10 d of age. All these parameters returned to control levels by d 15 postpartum. Electron microscopy of jejunal mucosal samples at 5, 10, and 15 d of age revealed that ethanol pups differed from controls by a fetal-like immature aspect of the enterocytes, which persisted up to d 15. The ontogenic upsurge in sucrase and the decline in lactase occurred at weaning with the same chronology in both groups, but the level reached by sucrase activity was about 50% lower in alcohol offspring than in controls. Except for moderate steatosis, the ultrastructure of hepatocytes was unaltered in sucklings.(ABSTRACT TRUNCATED AT 250 WORDS)


Effect of methylxanthines on diaphragmatic fatigue in the piglet.

Studies in adult animal and human subjects have suggested that the methylxanthine drugs can delay the onset or attenuate the severity of diaphragmatic fatigue. We have investigated the effect of aminophylline and caffeine on the pressure-generating capacity of the fatigued diaphragm in 1-mo-old piglets. Measurements of ventilation, transdiaphragmatic pressure, blood gases and pH, diaphragmatic electromyogram, diaphragmatic pressure-frequency curve (PdiFC), diaphragmatic blood flow, and end-expiratory lung volume were obtained at baseline, after 90 min of inspiratory resistive loaded breathing (IRL), and again 30 min after methylxanthine infusion while still on IRL. IRL resulted in a significant decrease in minute ventilation secondary to a fall in tidal volume. Spontaneously generated transdiaphragmatic pressure increased 7-fold from baseline. EMG activity increased to both segments of the diaphragm. Abdominal expiratory muscle activity was noted after the onset of IRL and was accompanied by a fall in end-expiratory lung volume. The PdiFC was significantly decreased from baseline after 90 min of IRL, demonstrating diaphragmatic fatigue. Aminophylline did not alter the PdiFC of the diaphragm. Diaphragmatic electromyogram and tidal volume increased. No change in diaphragmatic blood flow was demonstrated after infusion of aminophylline. Serum theophylline levels averaged 117 +/- 11 mumol/L (21 +/- 2 micrograms/mL). Caffeine administration did not alter the PdiFC or the diaphragmatic electromyogram during IRL. Blood flow to both segments of the diaphragm decreased after caffeine infusion. Serum caffeine levels averaged 86 +/- 30 mumol/L (16.6 +/- 5.9 micrograms/mL).(ABSTRACT TRUNCATED AT 250 WORDS)


The effect of outflow pressure upon thoracic duct lymph flow rate in fetal sheep.

Edema develops when lymph does not return to the venous circulation at a rate equal to the rate of capillary filtration. Fetal sheep develop edema as well as an increased central venous pressure while undergoing atrial pacing at 320 beats per min. We hypothesized that the increased central venous pressure augmented the appearance of fetal edema by impairing the return of thoracic duct lymph to the venous circulation. To investigate this hypothesis, we studied the effect of outflow pressure upon thoracic duct lymph flow in 10 unanesthetized fetal sheep who had low resistance lymph catheters placed in the cervical thoracic duct near its junction with the left jugular vein. After the ewe and fetus recovered for 5 d, we altered the outflow pressure of the lymph catheter by adjusting its height with respect to amniotic fluid pressure and measured the resultant change in thoracic duct lymph flow rate. We found that lymph flow rate was constant over the range of outflow pressures (central venous pressures) normally encountered but decreased in a linear fashion at pressures greater than 0.68 kPa (5.1 torr). Lymph flow stopped at an outflow pressure of 2.40 kPa (18 torr). The data points are best fit by two lines obtained by a piecewise linear regression rather than a single line obtained from a linear regression. We conclude that fetal thoracic duct lymph flow is sensitive to elevations in outflow pressure. Lymph flow begins to diminish at outflow pressures corresponding to central venous pressures commonly encountered in pathologic conditions and may augment the appearance of fetal edema.


Effects of inspiratory resistive loading on chest wall motion and ventilation: differences between preterm and full-term infants.

The ability to maintain effective tidal volume and minute ventilation during resistive loaded breathing depends on both adequate central neural respiratory output response and respiratory system mechanical properties such as respiratory muscle strength and chest wall stability. We hypothesized that chest wall instability limits the ability of the preterm (PT) infant to respond to inspiratory resistive loading (IRL) compared with full-term (FT) infants. To test this hypothesis, we subjected eight FT and 10 PT infants to IRL with loads of 1.3, 2, and 6 times intrinsic lung resistance and measured steady state tidal volume (VT), minute ventilation (VE), and chest wall motion. Thoracoabdominal asynchrony was measured by respiratory inductive plethysmography and quantitated by measuring the phase angle, theta, between rib cage and abdominal motion (0 degrees = synchronous motion, 180 degrees = paradoxic motion). At baseline, VT/kg (mL/kg, mean +/- SEM) was similar between PT (7.0 +/- 0.7) and FT (7.5 +/- 0.5) infants. VE/kg (mL/min/kg) was greater in PT (545 +/- 50) than in FT (385 +/- 33) infants (p < 0.05) as a result of increased respiratory frequency in the former. PT infants demonstrated significantly greater chest wall asynchrony (theta = 38 +/- 9 degrees) than FT infants (theta = 9 +/- 3 degrees) (p < 0.01). With the highest resistive loads, VT decreased significantly in the PT but not the FT infants. Furthermore, during IRL, VE decreased to 417 +/- 50 mL/min/kg (p < 0.05) and theta increased to 56 +/- 7 (p < 0.05) in the PT infants, whereas no significant change in either value was observed in the FT group.(ABSTRACT TRUNCATED AT 250 WORDS)


Natural surfactant instilled in premature lambs increases lung volume and improves ventilation homogeneity within five minutes.

The immediate effects on lung volume, ventilation homogeneity, and lung mechanics of tracheal instillation of surfactant were studied in premature lambs, gestational age 120-122 d, with respiratory distress syndrome. Six lambs received surfactant by tracheal instillation 25 min after delivery by cesarean section; five received only vehicle and served as controls. The lambs were studied for 60 min thereafter. Functional residual capacity was measured with a computerized tracer gas washin-washout technique using sulfur hexafluoride as tracer gas. A measure of ventilation inhomogeneity (pulmonary clearance delay) was also calculated from the washout curves. Pressure-volume curves were studied with an interrupter technique during deflation of the lungs from an airway pressure of 30 cm H2O. In the surfactant group, arterial oxygenation and ventilation homogeneity improved within 5 min of giving surfactant; major increases in functional residual capacity, vital capacity, and compliance occurred within 5 to 20 min and were followed by gradual further improvements. The pressure-volume curve thus increased in amplitude and became steeper, but the lung volumes at various inflation pressures, and compliance, remained constant when expressed as fractions of total lung capacity volume. It is concluded that an improvement in lung volume, respiratory mechanics, and ventilation homogeneity occurs very soon after surfactant instillation and that there is a phase of successive further improvement over the next hour. Although the amplitude of the pressure-volume curve varied considerably, its basic shape varied little. This suggests that opening of new distal airways by surfactant predominated over changes in the mechanics of already aerated lung regions.


Six new mutations in the ornithine transcarbamylase gene detected by single-strand conformational polymorphism.

We describe six new mutations in the ornithine transcarbamylase (OTC) gene found in patients with OTC deficiency. These mutations were detected by single-strand conformational polymorphism analysis of amplified genomic DNA and characterized by direct sequencing of double-stranded DNA. Three of the mutations were found in males who had neonatal onset of hyperammonemia. The mutations are a single base deletion (guanine) in exon 5 at nucleotide 403 causing a frame-shift error, a guanine to adenine substitution at the 3' end of intron 2 nucleotide 217 (-1) causing an acceptor splicing site error, and a guanine to adenine substitution at base 236 changing the code from glycine to glutamic acid at position 47 of the mature enzyme. Two different mutations were found in two males whose onset of clinical problems occurred after the neonatal period. One patient had a guanine to cytosine transversion in the sense strand of exon 3 at nucleotide 281 resulting in a substitution of threonine for arginine in position 62 of the mature OTC protein. This substitution changes the composition of the putative active site for carbamyl phosphate from Ser-Thr-Arg-Thr-Arg to Ser-Thr-Arg-Thr-Thr. The second patient has a guanine to thymine substitution at nucleotide 912 of the sense strand of exon 9, changing the code for leucine to phenylalanine in position 272 of the mature OTC protein. This changes a conserved domain of the gene likely to be the ornithine binding site from Phe-Leu-His-Cys-Leu-Pro to Phe-Leu-His-Cys-Phe-Pro.(ABSTRACT TRUNCATED AT 250 WORDS)


Pulsatile and sexually dimorphic secretion of luteinizing hormone in the human infant on the day of birth.

Experimental evidence indicates that the hypothalamic-pituitary-gonadal axis is operational and sexually dimorphic in the mammalian fetus and newborn. We examined the dynamics of human luteinizing hormone (LH) secretion in five male and three female infants on the day of birth, after 34-41 wk of gestation. The infants were polycythemic, and blood samples were obtained every 20 min for 160 to 360 min during a therapeutic, standardized, isovolumetric, partial exchange transfusion. Serum LH was measured by an immunoradiometric assay that does not cross-react with human chorionic gonadotropin. The serum profiles of LH presented a striking sex dimorphism with elevated LH levels in male compared with female newborns. Deconvolution analysis of all male LH profiles was consistent with a high-frequency, pulsatile secretory pattern. Testosterone, measured in a pooled serum sample of each infant, was 10-fold higher in male than in female newborns. These results document pulsatile and sexually dimorphic secretion of LH in the human infant as early as the first day of postnatal life. It is possible that the augmented LH secretion in the male newborn participates in the neonatal rise of the serum testosterone concentration.


Assessment of protein coding measures.

A number of methods for recognizing protein coding genes in DNA sequence have been published over the last 13 years, and new, more comprehensive algorithms, drawing on the repertoire of existing techniques, continue to be developed. To optimize continued development, it is valuable to systematically review and evaluate published techniques. At the core of most gene recognition algorithms is one or more coding measures--functions which produce, given any sample window of sequence, a number or vector intended to measure the degree to which a sample sequence resembles a window of 'typical' exonic DNA. In this paper we review and synthesize the underlying coding measures from published algorithms. A standardized benchmark is described, and each of the measures is evaluated according to this benchmark. Our main conclusion is that a very simple and obvious measure--counting oligomers--is more effective than any of the more sophisticated measures. Different measures contain different information. However there is a great deal of redundancy in the current suite of measures. We show that in future development of gene recognition algorithms, attention can probably be limited to six of the twenty or so measures proposed to date.


The TATA-binding protein participates in TFIIIB assembly on tRNA genes.

The TATA-binding protein TBP has been recently recognized as a general class III transcription factor. Using the gel shift assay to monitor initiation complex assembly on a yeast tRNA gene, we show that TBP is required for the TFIIIC-dependent assembly of TFIIIB. TFIIIB depleted of TBP by a simple chromatographic step does not bind stably to the TFIIIC-tDNA complex. Addition of yeast or human recombinant TBP allows the formation of a TFIIIB-TBP-TFIIIC-tDNA complex. The presence of TBP in the complex was inferred from the effect of anti-TBP antibodies and from the different migration properties of TFIIIB-TBP-tDNA complexes formed with yeast or human TBP.


Solution conformation of an oligonucleotide containing a urea deoxyribose residue in front of a thymine.

Urea residues are produced by ionizing radiation on thymine residues in DNA. We have studied an oligodeoxynucleotide containing a thymine opposite the urea residue, by one and two dimensional NMR spectroscopy. The urea deoxyribose exists as two isomers with respect to the orientation about the peptide bond. For the trans isomer we find that the thymine and urea site are positioned within the helix and are probably hydrogen bonded. The oligonucleotide adopts a globally B form structure although conformational changes are observed around the mismatch site. A minor species is observed, in which the urea deoxyribose and the opposite base adopt an extrahelical position and this corresponds to the isomer cis for the peptide bond.


Characterization and localization of cis-diamminedichloro-platinum(II) adducts on a purified oligonucleotide containing the codons 12 and 13 of H-ras proto-oncogene.

The use of substrates containing well defined adducts at precise sites, is required to perform a careful analysis of the toxic and mutagenic potential of a lesion. As a first step in this direction the octamer 5'-d(CCGGCGGT), containing the sequence of the codons 12 d(GGC) and 13 d(GGT) of the human H-ras gene, was reacted with the antitumoral drug cis-diamminedichloroplatinum(II). The platinated products have been purified by HPLC. A first set of experiments, including enzymatic digestions with nuclease P1 followed by alkaline phosphatase and acid-catalysed hydrolysis, allowed us to determine which bases were engaged in the cis-DDP lesions. Our results indicate that only guanine residues were chelated with cisplatin to yield bifunctional adducts. Furthermore, by performing enzymatic digestions with phosphodiesterases, we have located the adducts with respect to the 5' end of the octamer. Among the purified and characterized platinated oligonucleotides, three present a particular interest, since we have shown here that the cis-d(GpG) adduct is precisely situated either at the d(GGC) or at the d(GGT) or at both sites of their sequence.


A direct-repeat sequence of the human BiP gene is required for A23187-mediated inducibility and an inducible nuclear factor binding.

We have recently isolated a functional promoter encoding the human polypeptide-binding protein (BiP) gene from Burkitt's lymphoma cells by polymerase chain reaction (The EMBL Data Library accession number X59969, 1991). This promoter DNA segment (termed BiP670) was fused to the bacterial chloramphenicol acetyltransferase (CAT) reporter gene and expressed in NIH3T3 cells. BiP670 retains basal and Ca2+ ionophore A23187-inducible activities. Using 5' deletion assay, we found three basal expression elements (BEE) in the BiP670. Removal of the distal BBE (BBE3), which is contained in a segment spanning -368/-170, caused a 50% loss of the basal activity; removal together with the middle BBE (BBE2), which is contained in a segment spanning -170/-107, resulted in a further 30% loss of the activity. Further removal of the proximal BBE (BBE1), which spans -107/-39, abolished greater than 95% of the basal expression. In addition, an A23187-inducible element (AIE) appeared to be associated with the BBE1. At least a six-fold inducibility remained as long as the BiP promoter retained the sequences -107/-39. Using an in vitro gel mobility shift assay, an A23187-inducible nuclear factor (AINF) was detected from NIH3T3 cells. DNA binding competition experiments indicate that the -107/-39 segment contains a sequence motif which interacts with this cellular factor. Further analysis showed that the two direct repeats, ranging -108/-73 and -72/-40, are the target for AINF binding. A 3-4 fold increase of the AINF binding to both repeated sequences was detected from induced cells. Similar results were also demonstrated in HeLa cells, suggesting that transcriptional control of BiP gene expression in mammalian cells is conserved. These findings also imply that the identified nuclear factor may be important in mediating transcriptional activation of the BiP gene.


SEF1 binding is important for T cell specific enhancers of genes for T cell receptor-CD3 subunits.

A family of proteins, denoted SL3-3 enhancer factor 1 (SEF1), interacts with DNA sequences in the T cell specific enhancer of SL3-3 murine leukemia virus and in the enhancers of several other viruses. A putative SEF1 binding site was also identified in the T cell specific enhancer of the gene encoding the human T cell antigen receptor (TcR) associated CD3-epsilon polypeptide. In this study we show that the identified sequence is a strong SEF1 binding site, and that purified SEF1 proteins bind specifically to the sequence. We report also that the SEF1 binding site is important for T cell specific activation of transcription by the CD3-epsilon enhancer. We show that SEF1 binding sites are present also in the T cell specific enhancers of other subunits of the TcR-CD3 complex, and that SEF1 proteins appear to play a central role in the T cell specific expression of this set of enhancers.


BsuBI--an isospecific restriction and modification system of PstI: characterization of the BsuBI genes and enzymes.

The enzymes of the Bacillus subtilis BsuBI restriction/modification (R/M) system recognize the target sequence 5'CTGCAG. The genes of the BsuBI R/M system have been cloned and sequenced and their products have been characterized following overexpression and purification. The gene of the BsuBI DNA methyltransferase (M.BsuBI) consists of 1503 bp, encoding a protein of 501 amino acids with a calculated M(r) of 57.2 kD. The gene of the restriction endonuclease (R.BsuBI), comprising 948 bp, codes for a protein of 316 amino acids with a predicted M(r) of 36.2 kD. M.BsuBI modifies the adenine (A) residue of the BsuBI target site, thus representing the first A-N6-DNA methyltransferase identified in B. subtilis. Like R.PstI, R.BsuBI cleaves between the A residue and the 3' terminal G of the target site. Both enzymes of the BsuBI R/M system are, therefore, functionally identical with those of the PstI R/M system, encoded by the Gram negative species Providencia stuartii. This functional equivalence coincides with a pronounced similarity of the BsuBI/PstI DNA methyltransferases (41% amino acid identity) and restriction endonucleases (46% amino acid identity). Since the genes are also very similar (58% nucleotide identity), the BsuBI and PstI R/M systems apparently have a common evolutionary origin. In spite of the sequence conservation the gene organization is strikingly different in the two R/M systems. While the genes of the PstI R/M system are separated and transcribed divergently, the genes of the BsuBI R/M system are transcribed in the same direction, with the 3' end of the M gene overlapping the 5' end of the R gene by 17 bp.