Term pregnancy in a patient with McKusick-Kaufman syndrome.
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Biomedical subjects
Publications and source records attributed to E Cohen.
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Physicians were the most over-represented academic profession in the Third Reich. They participated in the Nazi programs of forced sterilization, systematic euthanasia, human experimentation, and mass genocide. Recent research has shifted from documenting the atrocities committed by medical professionals to elucidating the process by which the German medical community became integrated into the Nazi state. The Nazi doctrine attracted a profession in economic and political distress during the Weimar Republic. It drew physicians into its movement by appealing to the medical profession's pride and prosperity in the context of a philosophy that glorified contemporary medical practice. Physicians were attracted to the Nazi party's biologically based tenets that championed biomedical solutions to social problems. They perceived the Nazi regime as instrumental in improving their incomes, reducing unemployment by purging the profession of Jewish physicians, neutralizing the insurance bureaucracy, and re-structuring the profession. The Nazi government's popularity among doctors peaked in 1937, by which time physicians had already played an integral role in the orchestration of the Nazi state.
A case of multiple dorsal dislocations of the metacarpophalangeal joints is presented with a review of literature. Prompt recognition of the dislocation type is essential, followed by trial of closed reduction under proper anesthesia; open reduction is sometimes required. A short period of immobilization is needed, followed by intensive rehabilitation.
Interleukin-1 (IL-1), a cytokine secreted by activated macrophages, inhibits sexual behavior in female but not male rats. The present study examined the effects of IL-1 on sexual attractiveness of the injected animal and on the sexual responses exhibited by its mating partner. In Experiment 1, a male rat was placed with an estrous female, injected with either IL-1 beta (2 or 10 micrograms/kg) or saline. Males exhibited more mounts and intromissions per ejaculation and longer ejaculation latencies with IL-1- than with saline-injected females. In a second experiment, a male was placed with two estrous females, one injected with IL-1 beta (5 micrograms/kg) and the other with saline. Males performed less sexual behavior and spent less time with the IL-1-injected female. In a third experiment, an estrous female was placed with two males, one injected with IL-1 beta (5 or 20 micrograms/kg) and the other with saline. IL-1 had no effect on the time spent by the female with each male, and only the high dose reduced proceptive (courtship) behavior. In conclusion, IL-1 administration to females reduces the quality of the sexual act, thus reducing the chances for conception during infection, which is associated with spontaneous abortion and abnormal development of the fetus. In males, the chances for reproduction are less affected by IL-1, possibly because reproduction during infection is not as risky in males as in females.
Bioscavengers of organophophates (OP) have been examined as potential substitutes for the currently approved drug treatment against OP toxicity. The present work was designed to assess the ability of butyrylcholinesterase, purified from human serum (HuBChE), to prevent the toxicity induced by soman and VX in rhesus monkeys. The consistency of the data across species was then evaluated as the basis for the extrapolation of the data to humans. The average mean residence time of the enzyme in the circulation of monkeys following an intravenous loading was 34 hr. High bioavailability of HuBChE in blood (>80%) was demonstrated after intramuscular injection. A molar ratio of HuBChE:OP approximately 1.2 protected against an i.v. bolus injection of 2.1 x LD50 VX, while a ratio of 0.62 was sufficient to protect monkeys against an i.v. dose of 3.3 x LD50 of soman, with no additional postexposure therapy. A remarkable protection was also seen against soman-induced behavioral deficits detected in the performance of a spatial discrimination task. The consistency of the results across several species offers a reliable prediction of both the stoichiometry of the scavenging and the extent of prophylaxis with HuBChE against nerve agent toxicity in humans.
OBJECTIVES: (1) To prospectively evaluate the incidence of increased intraocular pressure (IOP) in patients suffering from chronic uveitis. (2) To identify the main factors responsible for an increase in the IOP among these patients. METHODS: Two hundred and one patients suffering from chronic uveitis were included. Enrolled patients had an initial IOP of 8-18 mmHg. The patients were treated and clinically monitored during a period of 4 years. The IOP was measured at each visit and its changes followed prospectively. All patients were followed up for at least 12 months after enrollment. RESULTS: Twenty-four (12%) of the 201 patients had IOP higher than 24 mmHg at two or more consecutive visits. Of these 24 patients, 19 suffered from bilateral uveitis and 5 had unilateral disease. Four of the 19 patients with bilateral uveitis developed a constant IOP higher than 24 mmHg in both eyes, while in 15 patients an IOP higher than 24 mmHg persisted only in one eye. A close association between the increased IOP and the use of corticosteroids was found in 18 of the 24 cases (75%). This association was ascertained in 16 of these patients by the decrease in IOP levels on discontinuation of the corticosteroid regimen and the renewed increase IOP was due to pupillary block in three cases (12.5%), to iris and angle neovascularization in two (8.3%), and to the inflammatory process per se in one case only (4.2%). CONCLUSIONS: This study demonstrates that a persistent elevation of the IOP in patients suffering from chronic uveitis is, in the majority of cases, associated with the use of corticosteroids.
PURPOSE: To compare the postoperative complications, visual outcome, and incidence of strabismus in children suffering from traumatic cataract corrected with contact lens or intraocular lens and to follow up the refractive changes in these eyes for an extended period of time. METHODS: Forty children, 2 to 13 years old at time of surgery for unilateral traumatic cataract, were followed up for 1.5 to 11 years. Seventeen children were corrected with contact lenses and 23 with intraocular lenses. Thirty-two underwent a primary posterior capsulectomy and anterior vitrectomy. RESULTS: The mean follow-up after surgery was 7.4 years for the children with contact lenses and 6.2 years for those with intraocular lenses. The incidence of secondary surgical interventions was higher among the children corrected with contact lenses. The eight children (five with contact lenses, three with intraocular lenses) who did not undergo primary posterior capsulectomy had Nd:YAG capsulectomy within 1 year after surgery. Fifteen of the 23 children with intraocular lenses (65.2%) achieved a best-corrected visual acuity of 20/40, and 17 children (73.9%) had a final visual acuity of 20/50, but only five of 17 children with contact lenses (35.3%) achieved this level of visual acuity. CONCLUSIONS: Correction of unilateral aphakia by intraocular lens in children after traumatic cataracts results in better final visual acuities and binocularity with a smaller incidence of strabismus than when correction is carried out by contact lens. Intraocular lens implantation should be considered the primary aphakic correction in children with traumatic cataract.
The endogenous opiate system plays a role in fetal sexual differentiation during development. We examined long-term effects of prenatal morphine on adult sexual behavior in male rats. Pregnant Fischer 344 rats were given increasing doses of morphine (0.75-12.0 mg/day) in slow-release emulsion during gestational days 12-18. Control rats were injected with vehicle and were either pair-fed with morphine rats or ad lib fed. At birth, all litters were culled to eight pups and fostered to naive dams. Testing began when rats were 10-12 weeks old. Masculine behavior was assessed using receptive stimulus females and recording instances of mount, intromission, and ejaculation. Feminine receptivity of the male rats was assessed following castration and priming with ovarian hormones; lordosis quotient of the experimental males was recorded using stimulus male studs. Males prenatally exposed to morphine exhibited normal rates of male copulatory behavior but a significantly higher lordosis quotient, suggesting that prenatal morphine induced long-lasting feminizing effects.
Conditioned place preference (CPP) is a commonly used method for assessing the rewarding qualities of drugs, including opiates. In the present study, we examined long-term effects of prenatal morphine on morphine-associated place preference. Pregnant Fischer 344 rats were given increasing doses of morphine (0.75-12.0 mg/day) in slow-release emulsion during gestational days 12-18. Control rats were injected with vehicle and were fed either with morphine rats or ad libitum. At birth, all litters were culled to 8 pups and fostered to naive dams. Testing began when rats were 10-12 weeks old. Rats prenatally exposed to morphine exhibited a significantly higher preference for the morphine-paired compartment, suggesting that prenatal morphine induces a long-lasting enhancement of its reinforcing effect. Thus, prenatal morphine may result in enhanced activity and/or sensitivity of the endogenous opiate system, thereby placing the organism at higher risk for opiate drug abuse.
OBJECTIVE: The purpose of the study is to evaluate whether a posterior capsulectomy combined with anterior vitrectomy is a necessity in pediatric cataract. DESIGN: The incidence of posterior capsule opacification, the need for additional surgical interventions, and the influence of a primary posterior capsulectomy after cataract surgery in children were evaluated. The analysis was carried out by studying patients' records retrospectively or after prospective follow-up. PARTICIPANTS: In 94 eyes (69 aphakic and 25 pseudophakic), the medical records were studied retrospectively. Twenty-eight eyes (18 aphakic and 10 pseudophakic) were observed prospectively during 1 year after surgery. In 20 eyes (6 aphakic and 14 pseudophakic) of 10 patients with bilateral cataract, a prospective comparison between the 2 eyes of the same patient also was carried out. INTERVENTION: Cataract surgery through the limbus with or without a primary posterior capsulectomy was performed in 114 eyes (43 of these received a posterior chamber intraocular lens [IOL] and 71 remained aphakic). In 28 eyes, the surgery was carried out by way of the pars plana (6 eyes received an anterior chamber IOL and 22 remained aphakic). MAIN OUTCOME MEASURES: Incidence of posterior capsule opacification, the need for secondary surgical intervention, and visual acuity were measured. RESULTS: Opacification of the posterior capsule is observed in all children's eyes when a primary posterior capsulectomy (combined with an anterior vitrectomy) was not carried out. Earlier secondary cataract formation is associated with a younger age and with implantation of an IOL. Eyes undergoing a primary opening of the posterior capsule during the initial surgery of children with bilateral cataract achieved, in most cases, a better visual acuity than did their fellow eyes. CONCLUSION: Although possibly a choice in older children, a primary posterior capsulectomy combined with anterior vitrectomy is a must in younger children and particularly when implantation of an IOL is planned.
After working side by side with three generations, the authors unfolds a story of survival. This poignant testimony to humanity focuses on the courage and the strength of the people of North Dakota during the 1997 flood.
A 12-day-old infant presented with marked cyanosis of the right lower limb, mimicking vascular compromise. Physical examination, plain radiography, and laboratory evidence of systemic infection suggested septic arthritis of the hip. Pyoarthrosis was verified by needle aspiration and open drainage. Streptococcus pneumoniae was isolated. A cyanotic limb may be an atypical presentation for septic arthritis in the newborn.
Palinavir is a potent inhibitor of the human immunodeficiency virus type 1 (HIV-1) and type 2 (HIV-2) proteases. Replication of laboratory strains (HIV-1, HIV-2, and simian immunodeficiency virus) and HIV-1 clinical isolates is inhibited by palinavir with 50% effective concentrations ranging from 0.5 to 30 nM. The average cytotoxic concentration of palinavir (35 microM) in the various target cells indicates a favorable therapeutic index. Potent antiviral activity is retained with increased doses of virus and with clinical isolates resistant to zidovudine (AZT), didanosine (ddI), or nevirapine. Combinations of palinavir with either AZT, ddI, or nevirapine demonstrate synergy or additivity in the inhibition of HIV-1 replication. Palinavir retains anti-HIV-1 activity when administered postinfection until times subsequent to the reverse transcription step. In chronically infected CR-10 cells, palinavir blocks Gag precursor polyprotein processing completely, reducing greater than 99% of infectious particle production. The results indicate that the antiviral activity of palinavir is specific to inhibition of the viral protease and occurs at a late stage in the replicative cycle of HIV-1. On the basis of the potent in vitro activity, low-level cytotoxicity, and other data, palinavir was selected for in-depth preclinical evaluation.
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Protein phosphatase 2A (PP2A) plays a central role in essential phosphorylation-dependent signal transduction pathways. It is also a principal target for many natural toxicants (cantharidin, microcystins, diarrhetic shellfish poisons) and a synthetic herbicide (endothall). This study develops a cellular model to explore the toxicology of PP2A inhibitors by use of a [3H]cantharidic acid ([3H]CA) ligand binding assay to quantify interactions at the toxicant site and cell viability to evaluate in vivo toxicity. Mouse neuroblastoma (N1E-115) cells are similar to mouse brain with respect to the affinity (12-15 nM), number (B(max), 9-22 pmol/mg protein) and ligand specificity of this binding site. In addition, the competitive potency of ten analogs of CA (including endothall) and two potent diarrhetic shellfish poisons (okadaic acid and calyculin A) is correlated (r2 = .9) with and therefore predictive of their cytotoxicity. The only exception is microcystin LR which is a potent inhibitor at the binding site but is not cytotoxic, possibly reflecting a lack of cellular uptake. ATP and several other phosphorus-containing bifunctional acids inhibit [3H]CA binding by phosphorylation-independent pathways; pyrophosphate apparently acts as a competitive inhibitor. Mn++ and five other divalent cations are also inhibitors with a unique action of Mn++ at 25 to 50 microM in increasing [3H]CA binding, which suggests a specific role in PP2A function. Neuroblastoma cells are therefore suitable to study the mechanisms by which the toxicant, ATP and Mn++ binding sites regulate PP2A activity and cell physiology.
The first part of this article reviews the distribution of ventilation (V) and perfusion (Q) during the supine and the lateral decubitus position. The changes in the V/Q during the lateral position with and without paralysis are discussed. The second part evaluates the degree of transpulmonary shunt during one lung ventilation (OLV) and the role of hypoxic pulmonary vasoconstriction in maintaining arterial oxygenation. Finally, the influence and the use of nitric oxide during OLV is reviewed.
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