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OBJECTIVES: Poor communication is a major contributor to sentinel events in hospitals. Suboptimal communication between physicians and nurses may be due to poor understanding of team members’ roles. We sought to evaluate the impact of a shadowing experience on nurse–resident interprofessional collaboration, bidirectional communication, and role perceptions. METHODS: This mixed-methods study took place at 2 large academic children’s hospitals with pediatric residency programs during the 2018–2019 academic year. First-year residents and nurses participated in a reciprocal, structured 4-hour shadowing experience. Participants were surveyed before, immediately after, and 6 months after their shadowing experience by using an anonymous web-based platform containing the 20-item Interprofessional Collaborative Competency Attainment Survey, as well as open-ended qualitative questions. Quantitative data were analyzed via linear mixed models. Qualitative data were thematically analyzed. RESULTS: Participants included 33 nurses and 53 residents from the 2 study sites. The immediate postshadowing survey results revealed statistically significant improvements in 12 Interprofessional Collaborative Competency Attainment Survey question responses for nurses and 19 for residents (P ≤ .01). Subsequently, 6 questions for nurses and 17 for residents revealed sustained improvements 6 months after the intervention. Qualitative analysis identified 5 major themes related to optimal nurse–resident engagement: effective communication, collaboration, role understanding, team process, and patient-centered. CONCLUSIONS: The reciprocal shadowing experience was associated with an increase in participant understanding of contributions from all interprofessional team members. This improved awareness may improve patient care. Future work may be conducted to assess the impact of spread to different clinical areas and elucidate patient outcomes that may be associated with this intervention.

AIM Unnecessary antibiotic prescriptions to treat otitis media (OM) contribute to adverse drug reactions, increased cost and antibiotic resistance. Clinical care guidelines can help promote consistent treatment of conditions such as OM. This study evaluates adherence before and after implementation of an institutional guideline for the diagnosis and treatment of paediatric OM. METHODS A retrospective chart review was performed to collect encounter information for paediatric patients seen within a primary care clinic network and diagnosed with OM before and after full implementation of a clinical care guideline. Patient cohorts from 2013 and 2016 were compared to determine which factors, including age, symptoms and diagnosis, were associated with treatment guideline adherence. RESULTS Comparison of encounters from 2013 (n = 418) to 2016 (n = 635) revealed a significant difference in adherence to the 2013 Michigan Medicine Otitis Media Guideline. Overall adherence increased from 61.2% in 2013 to 70.6% in 2016 (χ2 = 9.85, P

Mistreatment in the learning environment is associated with negative outcomes for trainees. While the Association of American Medical Colleges (AAMC) annual Graduation Questionnaire (GQ) has collected medical student reports of mistreatment for a decade, there is not a similar nationally benchmarked survey for residents. The objective of this study is to explore the prevalence of resident experiences with mistreatment.Residents at three academic institutions were surveyed using questions similar to the GQ in 2018. Quantitative data were analyzed based on frequency and Mann-Whitney U tests to detect gender differences.Nine hundred ninety-six of 2682 residents (37.1%) responded to the survey. Thirty-nine percent of residents reported experiencing at least one incident of mistreatment. The highest reported incidents were public humiliation (23.7%) and subject to offensive sexist remarks/comments (16.0%). Female residents indicated experiencing significantly more incidents of public embarrassment, public humiliation, offensive sexist remarks, lower evaluations based on gender, denied opportunities for training or rewards, and unwanted sexual advances. Faculty were the most frequent instigators of mistreatment (66.4%). Of trainees who reported experiencing mistreatment, less than one-quarter reported the behavior.Mistreatment in the academic learning environment is a concern in residency programs. There is increased frequency among female residents.

Physician attire may influence the parent-provider relationship. Previous studies in adult and outpatient pediatrics showed that formal attire with a white coat was preferred. We aimed to describe parent preferences for physician attire in the neonatal intensive care unit (NICU). We surveyed 101 parents in a level IV NICU. The survey included photographs of a physician in seven different attires. Attire was scored in five domains and parents selected the most preferred attire in different contexts. All attires were compared with formal attire with white coat. Descriptive statistics, Fisher's exact tests, and one-way analysis of variance were used to compare parent responses. Scrubs without white coat (40.8 [7.0]) and formal attire without white coat (39.7 [8.0]) had the highest mean (standard deviation) composite preference scores. However, no significant differences between formal attire with white coat (37.1 [9.0]) versus any other attire were observed. When asked to choose a single most preferred attire, scrubs with a coat (32%) and formal with a coat (32%) were chosen most often, but preferences varied by clinical context and parent age. For example, parents preferred surgical scrubs for physicians performing procedures. Parents indicated that physician attire is important to them but does not influence their satisfaction with care. Although parents generally favored formal attire and scrubs, the variations based on the context of care and lack of significant preference of one attire suggests that a single dress code policy for physicians in a NICU is unlikely to improve the patient-provider relationship.· Adult patients prefer doctors to wear formal attire.. · Physician attire preferences influenced by age, setting, and context of care.. · Little is known about physician attire preferences of the parents of neonates.. · Unlike adult patients, NICU parents did not prefer formal attire with a white coat..

Background: Despite increasing representation of women in medicine, gender bias remains pervasive. The authors sought to evaluate speaker introductions by gender in the grand rounds of multiple specialties at a large academic institution to understand the cultural context of this behavior and identify predictors of formality. Materials and Methods: The authors reviewed grand rounds recordings of speakers with doctorates presenting to the departments of family medicine, general surgery, internal medicine, obstetrics and gynecology, and pediatrics at one institution from 2014 to 2019. The primary outcome was whether a speaker's professional title was used as the first form of address. The authors assessed factors correlated with professional introduction using multivariable logistic regression. Results: Speakers were introduced professionally in 346/615 recordings (56.3%). Female introducers were more likely to introduce speakers professionally (odds ratio [OR]: 2.52). A significant interaction existed between speaker gender and home institution: female speakers visiting from an external institution were less likely than male external speakers to be introduced professionally (OR: 0.49), whereas female speakers internal to the institution were more likely to be introduced professionally than male internal speakers (OR: 1.75). Use of professional titles varied by specialty and was higher than average for family medicine (83.2%), surgery (75.8%), and pediatrics (64.0%) and lower for internal medicine (37.5%) and obstetrics and gynecology (50.7%). Conclusions: These findings suggest a complex relationship between gender and formality of introduction that merits further investigation. Understanding differences in culture across specialties is important to inform efforts to promote equity.

Background: Returning to work and lack of support for expressing breast milk (pumping) at work is often cited as a reason that mothers discontinue breastfeeding, particularly among female ...

Lotus birth is the practice of leaving the umbilical cord uncut until separation occurs naturally. Our case series report describes delivery characteristics, neonatal clinical course, cord and placenta management, maternal reasons for a lotus birth, and desire for future lotus births. Between April 2014 and January 2017, six lotus births occurred. Mothers (four of the six) were contacted by phone after giving birth. A chart review was completed on each patient to evaluate if erythromycin ointment, hepatitis B vaccine, and vitamin K (intramuscular or oral) were administered, treatment of the placenta, maternal group B streptococcus status, postnatal infant fevers, infant hemoglobin or hematocrit levels, jaundice requiring phototherapy, and infant readmissions. Three of the six families decided to cut the cord before hospital discharge. No infections were noted. All contacted mothers would elect for a lotus birth again (4/6). One hepatitis B vaccine was given; all others declined perinatal immunization.

BACKGROUND: Pediatric hypertension can predispose children to adult cardiovascular disease and can be the first presentation of significant medical conditions. However, it is recognized that pediatric hypertension is underdiagnosed due to difficulty identifying elevated blood pressures (BPs). Evidence suggests that electronic medical record (EMR) automated alerts (e.g. best practice advisory, BPA) can improve detection rate of pediatric hypertension. However, published efforts have been variably successful. We developed a multi-level BPA to improve the detection rate of elevated BPs in a large academic pediatric program. METHODS: A retrospective analysis …

What's New Communication of medical students' pediatric milestone assessments and individual learning plans from medical schools to pediatric residency directors allows for effective educational handovers promoting the continuum of education. Existing undergraduate medical education assessments can provide meaningful data to determine most pediatric milestone levels.

1. Morgen Govindan, MD* 2. Heather L. Burrows, MD, PhD* 1. *Department of Pediatrics and Communicable Diseases, Mott Children’s Hospital, University of Michigan Medical School, Ann Arbor, MI Neonatal brachial plexus injury presents as weakness or paralysis of the upper extremity or extremities at birth, most often related to stretching of the brachial plexus in the perinatal period. Early recognition and management in the newborn period can significantly impact outcomes. Therefore, it is important for pediatricians to be knowledgeable regarding the clinical spectrum of injury, prognosis, and treatment options. The incidence of brachial plexus injury ranges from 0.4 to 4 per 1,000 births. The primary risk factors are shoulder dystocia and macrosomia (birthweight >4,000 g). Other risk factors include maternal diabetes or obesity, prolonged labor, and delivery with forceps or a vacuum extractor. Although cesarean delivery decreases the risk of brachial plexus injury, it does not eliminate it, and it carries other risks for both mother and infant. The brachial plexus is composed of nerve roots C5 through T1 and can be divided into the upper (C5 and C6), middle (C7), and lower (C8 and T1) trunks. Peripheral nerves arising from the plexus innervate the muscles of the upper extremity. There are multiple ways to classify brachial plexus injuries. One example uses the Narakas classification system, which grades the severity of injury from group I to IV, with lower groups being associated with higher rates of spontaneous recovery. Group I represents injury to the upper trunk alone, C5 and C6. The shoulder is adducted and internally rotated with an extended elbow, commonly described as the “waiter’s tip” position known as Erb-Duchenne palsy. Function of the wrist and hand is maintained, …

Introduction Addressing vaccine hesitancy and the antivaccination movement has become part of pediatric practice, particularly in the context of the reemergence of previously eradicated vaccine-preventable illnesses. Oftentimes, trainees do not feel comfortable speaking to patients and families who are hesitant to vaccinate or wish to follow alternative schedules. This curriculum was developed in order to address this identified gap in pediatric trainee education. Methods The curriculum begins with a simulated patient encounter with a vaccine-hesitant parent. The trainees undergo a series of lectures on vaccine-preventable illnesses, vaccine safety and administration, personal experience with a family affected by vaccine-preventable illnesses, and communication techniques with role-play opportunities. Finally, trainees undergo the simulated patient encounter again. In reviewing our intervention, we compared pre- and postcurriculum assessments to see how residents perceived their experience and comfort. Simulated patient encounters were graded on a Likert scale by experienced faculty. Results We administered our curriculum to 26 pediatric interns. Our results showed that residents improved in self-competence and confidence in addressing vaccine concerns with vaccine-hesitant families. Following the curriculum, residents were all willing to engage vaccine-hesitant families when the opportunity arose. Furthermore, based on graded simulated patient encounters, our residents improved in multiple aspects of their knowledge, comfort, and counseling techniques. Discussion Our study demonstrated that providing this educational curriculum positively influenced trainees' engagement in conversation with vaccine-hesitant families.

Human cells have evolved several mechanisms for responding to damage created by ionizing radiation. Some of these responses involve the activation or suppression of the transcriptional machinery. Other responses involve the downregulation of enzymes, such as topoisomerase I, which appear to be necessary for DNA repair or apoptosis. Over the past five years, many studies have established links between DNA damage, activation of transcription factors that are coupled to DNA repair mechanisms, increased gene transcription and altered cell cycle regulation to allow for repair or cell death via apoptosis or necrosis. Together these factors determine whether a cell will survive with or without carcinogenic consequences. The immediate responses of human cells to ionizing radiation, in terms of sensing and responding to damage, are therefore, critical determinants of cell survival and carcinogenesis.

Objectives To characterize pediatric patient contacts with their primary care clinic in the 2 days preceding a visit to the emergency department (ED) and explore how the type of clinic contact relates to ED resource use. Study design We conducted a retrospective chart review of 368 pediatric ED visits in the first 7 days of each month, from September 2012 to August 2013. Visits were included if the family contacted their child's general pediatric clinic in the study health system in the 2 days preceding the ED visit. Descriptive statistics were calculated. Primary outcomes were ED resource use (tests, treatments) and disposition (admission or discharge). Outcomes by type of clinic contact were compared with χ 2 statistics. Results Of 1116 records with ED visits in the 12 study weeks extracted from the electronic medical record, 368 ED visits met inclusion criteria. Most ED visits followed a single clinic contact (78.8%). Of the 474 clinic contacts, 149 were in-person visits, 216 phone calls when clinic was open, and 109 phone calls when clinic was closed. ED visits that followed an in-person clinic contact with advice to go to the ED had significantly greater rates of testing and admission than those advised to go to the ED after phone contact and those never advised to go to the ED. Conclusions In-person clinic visits with advice to go to the ED were associated with the greatest ED resource use. Limitations include a study of a single health system without a uniform process for triaging patients to the ED across clinics.

Organ-specific expression of a cre recombinase transgene allows for the analysis of gene function in a particular tissue or cell type. Using a 4.6 kb promoter from the mouse glycoprotein hormone alpha-subunit (alphaGSU or Cga) gene, we have generated and characterized a line of transgenic mice that express cre recombinase in the anterior and intermediate lobes of the pituitary gland. Utilizing a cre-responsive reporter transgene, alphaGSU-cre transgene expression was detected in the pituitary primordium and in all five cell types of the adult anterior pituitary. alphaGSU-cre transgene activity was also detected in the cardiac and skeletal muscle. Little or no activity was evident in the gonads, adrenal glands, brain, ventromedial hypothalamus, or kidneys. The alphaGSU-cre transgenic mice characterized here will be a valuable tool for examining gene function in the pituitary gland.

Corticotropin-releasing hormone (CRH) is widely recognized as the primary mediator of the neuroendocrine and behavioral responses to stress, including stress-induced anxiety. The biological activity of CRH and other mammalian CRH-like peptides, such as urocortin, may be modulated by CRH-binding protein (CRH-BP). To assess directly the CRH-BP function, we created a mouse model of CRH-BP deficiency by gene targeting. Basal adrenocorticotropic hormone and corticosterone levels are unchanged in the CRH-BP-deficient mice, and the animals demonstrate a normal increase in adrenocorticotropic hormone and corticosterone after restraint stress. In contrast, adult male CRH-BP-deficient mice show significantly reduced body weight when compared with wild-type controls. CRH-BP-deficient mice also exhibit a significant increase in anxiogenic-like behavior as assessed by the elevated plus maze and defensive withdrawal tests. The increased anorectic and anxiogenic-like behavior most likely is caused by increased “free” CRH and/or urocortin levels in the brain of CRH-BP-deficient animals, suggesting an important role for CRH-BP in maintaining appropriate levels of these peptides in the central nervous system.

This resource is a part of a seven-module curriculum intended to provide teaching faculty caring for well newborns with accessible, approachable, easily delivered, hands-on tools for bedside teaching in the newborn nursery. The seven modules are linked. This module focuses on newborn jaundice. Jaundice is an exceedingly common problem in the early newborn period, yet the approach to the physical examination and evaluation of jaundiced infants will vary depending on infant age, condition, and risk factors. The appropriate management of neonatal jaundice depends on one's ability to distinguish infants at risk for developing jaundice from those at risk for developing neurotoxicity from jaundice. In addition, the physician must be able to recognize the uses and limitations of published guidelines and to correctly interpret findings on the physical examination. This module is designed to review the clinically relevant aspects of neonatal hyperbilirubinemia that presents in the first days of life and then translate that knowledge into informed management of a jaundiced infant. It has been used in the newborn nursery setting to stimulate thought and discussion about jaundice. It has primarily been used by attending physicians who are teaching pediatric residents and medical students, but could also be used by a senior resident who is functioning in a supervisory or teaching role. Medical students and resident physicians have given very positive feedback about the material presented, and attending physicians have found it easy to use. Third-year medical students and pediatric residents were evaluated using a 5-point Likert scale (1 = strongly disagree, 5 = strongly agree). Results are as follows: “Presentation was well-organized and presented clearly.” (4.57 average); “Audiovisual aids were helpful.” (4.43); “Topic was important and useful.” (4.71); “Presentation was appropriate for my level of training.” (4.71); “Presenter achieved stated objectives.” (4.71); “Overall, teaching was effective.” (4.43); and “This presentation should be continued.” (4.71).

Introduction This resource is a part of a seven module curriculum intended to provide teaching faculty caring for well newborns with accessible, approachable, easily delivered, hands-on tools for bedside teaching in the newborn nursery. The seven modules are linked. Methods This module focuses on acquiring the skills to complete a newborn physical examination. Also included is a guide to newborn reflexes. This checklist has been used for third-year medical students, pediatric, medicine-pediatric and family medicine interns, and physician assistant students at three different institutions. Results This checklist was evaluated by randomizing 22 medical students into one of two groups: students who received feedback using this checklist and students who received routine feedback without using this checklist (control group). At the end of their one week newborn rotation, students' newborn physical exam skills were assessed by a blinded pediatrician. Using the checklist, students were given a score (0 = not done, 1 = needs improvement, 2 = done). Students who had received feedback using this checklist had a higher average score on individual items (average score 1.72 vs. 1.55 for control group, not significant). Discussion Attending physicians found the checklists easy to understand and easy to use. They felt that the checklists improved the quality of the feedback that the students received by covering more areas and by focusing on specific points. This checklist has been part of the University of Michigan student and intern curriculum since 2008.

Pituitary gland is a small endocrine gland located at the base of the brain under the optic chiasm and the arachnoid membrane, in a bony indentation called the sella turcica. Its name comes from the Greek hypophysis, which means undergrowth. The role of the pituitary gland is the regulated synthesis and secretion of polypeptide hormones that are essential for the development and function of many other organs in the body. Releasing hormones and inhibiting factors reach the anterior pituitary via hypothalamic neurons that terminate in the capillary beds of the median eminence, just dorsal to the pituitary gland. These capillary beds are connected to the hypophyseal portal vessels that nourish the anterior pituitary. In response to these stimulatory stimulatory factors, pituitary hormones are released into hypophyseal portal blood vessels and carried through the blood stream to their target organs. An intriguing feature of pituitary development is the initial organization of the cell types into discrete patches and the loss of this spatial organization as the organ expands. The rodent pituitary is composed of three lobes. The posterior pituitary (neurohypophysis or pars nervosa) is derived from neural ectoderm and contains the nerve terminals that secrete oxytocin and vasopressin. The intermediate lobe (pars intermedia) and anterior lobe are both derived from oral ectoderm. The bulk of the anterior lobe (pars distaIis) is at the same level as the intermediate lobe, but a portion of it known as the pars tuberalis extends dorsally along the pituitary stalk.

CRH is the key physiological mediator of the endocrine, autonomic, and behavioral responses to stress. The recent characterization of urocortin, a new mammalian CRH-like ligand, adds to the complexity of the CRH system. Both CRH and urocortin mediate their endocrine and/or synaptic effects via two classes of CRH receptors. Similarly, both CRH and urocortin bind to the CRH-binding protein (CRH-BP). This secreted binding protein is smaller than the CRH receptors, but binds CRH and urocortin with an affinity equal to or greater than that of the receptors, and blocks CRH-mediated ACTH release in vitro. Several regions of CRH-BP expression colocalize with sites of CRH synthesis or release, suggesting that this binding protein may have a profound impact on the biological activity of CRH (or urocortin). While in vitro and in vivo studies have characterized the biochemical properties and regulation of the CRH-BP, animal models of altered CRH-BP expression can provide additional information on the in vivo role of this important modulatory protein. This review focuses on three mouse models of CRH-BP overexpression or deficiency. These animal models show numerous physiological changes in the HPA axis and in energy balance, with additional alterations in anxiogenic behavior. These changes are consistent with the hypothesis that CRH-BP plays an important in vivo modulatory role by regulating levels of "free" CRH and other CRH-like peptides in the pituitary and central nervous system.

The anterior lobe of the pituitary gland is derived from the oral ectoderm early in gestation. A variety of techniques have been used to understand how early precursor cells differentiate to form the five major cell types that populate the adult anterior lobe. Current evidence suggests that corticotropes arise from a lineage distinct from that of the other four cell types. The cells of the other lineage branch - thyrotropes, gonadotropes, somatotropes and lactotropes - appear to be related because of their dependence on common transcription factors and the frequent occurrence of cells that produce multiple hormones. While thyrotropes arise through two routes, the lineage related to somatotropes and lactotropes appears to be the most important for hormone production. Each cell type can populate the organ and function in the absence of the other cell types, except for lactotropes, which have a strong dependence on somatotropes. Our current knowledge of anterior pituitary cell lineage relationships may contribute to a better understanding of the origin of pituitary adenomas and tumors.

Corticotropin-releasing hormone (CRH) is the primary hypothalamic releasing factor that mediates the mammalian stress response. The CRH-binding protein (CRH-BP) is secreted from corticotropes, the pituitary CRH target cells, suggesting that the CRH-BP may modulate hypothalamic-pituitary-adrenal (HPA) axis activity by preventing CRH receptor stimulation. Transgenic mice were generated that constitutively express elevated levels of CRH-BP in the anterior pituitary gland. RNA and protein analyses confirmed the elevation of pituitary CRH-BP. Basal plasma concentrations of corticosterone and adrenocorticotropin hormone (ACTH) are unchanged, and a normal pattern of increased corticosterone and ACTH was observed after restraint stress. However, CRH and vasopressin (AVP) mRNA levels in the transgenic mice are increased by 82 and 35%, respectively, to compensate for the excess CRH-BP, consistent with the idea that CRH-BP levels are important for homeostasis. The transgenic mice exhibit increased activity in standard behavioral tests, and an altered circadian pattern of food intake which may be due to transgene expression in the brain. Alterations in CRH and AVP in response to elevated pituitary CRH-BP clearly demonstrate that regulation of CRH-BP is important in the function of the HPA axis.

The various hormones of the anterior pituitary are expressed in a specific temporal and spatial pattern during organogenesis, which is interpreted as a reflection of a temporal pattern of pituitary cytodifferentiation. The first pituitary transcripts detected are from alpha GSU, which encodes the alpha-subunit common to the gonadotropins (FSH and LH) and TSH. TSH beta-subunit transcripts appear several days later but precede transcription of the GH and FSH beta and LH beta-subunit genes. To determine the lineage relationship between the alpha-subunit-expressing cells and the other hormone-producing cells of the anterior pituitary, we have employed the technique of transgene ablation. Transgenic mice were generated that express either the normal diphtheria toxin A chain or a 30-fold less active attenuated version in pituitary gonadotrope and thyrotrope cells. The absence of detectable transcripts for alpha-subunit, TSH beta-subunit, or LH beta-subunit by in situ hybridization confirmed that ablation was complete. In spite of the absence of gonadotropes and thyrotropes, the GH and ACTH-producing cells developed normally. These results imply that although thyrotropes appear early in pituitary development, they are not obligate intermediates in the developmental pathway. Instead, commitment to individual differentiated pituitary cell fates must occur autonomously or before the expression of currently known differentiation markers.

Normal human fibroblast (i.e., GM2936B, GM2907A, and IMR-90) and cancer-prone human fibroblast (i.e., Fanconi's anemia, Bloom's syndrome, and Ataxia telangiectasia) cells demonstrated the induction of intracellular and extracellular levels of tissue-type plasminogen activator (t-PA) at 6 and 12 hr, respectively, following ionizing radiation. Induced t-PA enzymatic activities following ionizing radiation were blocked by actinomycin D treatments. t-PA enzymatic activities were induced over 14-fold in Ataxia telangiectasia cells, over 9-fold in Bloom's syndrome cells, and over 6-fold in Fanconi's anemia cells, as compared to normal human fibroblasts. Similarly, the induction of t-PA mRNA levels in cancer-prone cells were between 5- to 10-fold higher than those observed in normal cells following equitoxic doses of ionizing radiation. Temporal induction of t-PA mRNA levels for normal and cancer prone human cells were consistent with quantifiable enzymatic activities. The elevated induction of an intracellular protease (i.e., t-PA) in cancer-prone human cells is reminiscent of an “SOS”-like response observed in yeast and bacteria.

Little is known about the molecular mechanisms responsible for the survival recovery process(es) (known as potentially lethal damage repair), which occurs in mammalian cells following ionizing radiation. Previously, we presented data indicating a role for the DNA unwinding enzyme, topoisomerase I, in DNA repair. We now demonstrate that camptothecin, a specific inhibitor of topoisomerase I, causes dramatic radiosensitization of an extremely resistant human melanoma (U1-Mel) cell line. Camptothecin radiosensitized U1-Mel cells when it was administered either during or immediately following x-irradiation. U1-Mel cells were optimally radiosensitized with 4 microM camptothecin for a period of 4-6 hrs after x-irradiation. Enhanced cell killing by camptothecin was proportional to the initial extent of damage created by x-irradiation; the higher the dose of ionizing radiation, the greater the radiosensitization. The apparent synergy observed with camptothecin and x-rays was irreversible; camptothecin-treated U1-Mel cells were not able to carry out PLDR in a 48 hr period after the drug was removed. We hypothesize that the administration of camptothecin causes lesion modification through a topoisomerase I-mediated mechanism. These data support a role for topoisomerase I in DNA repair and indicate that camptothecin, or more effective derivatives, may have clinical use.