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R J Hardy

Publications and source records attributed to R J Hardy.

At least 55 records · Page 3Linked to original sources
PubMed1997

Impact of HIV/AIDS on life expectancy in the United States.

OBJECTIVES: The potential gains in life expectancy of the US population by the partial and total elimination of deaths from HIV/AIDS were compared with that of deaths from heart disease and malignant neoplasms. METHODS: The data from the 1992 advanced mortality report and detailed information provided by the National Center for Health Statistics were analysed by using the partial multiple decrement life-table technique. RESULTS: For the total population of the United States in 1992, the gains in future life expectancy through the elimination of deaths from HIV/AIDS, heart disease and malignant neoplasms were 0.34, 3.25 and 3.21 years, respectively. The gains in life expectancy in those of working age 15-64 years) through the elimination of deaths from these three causes of deaths were 0.20, 0.40 and 0.55 years, respectively. Race/sex-specific calculations indicate that the total elimination of deaths from HIV/AIDS, heart disease and malignant neoplasms in white men of working age resulted in increased life expectancy of 0.28, 0.54 and 0.53, respectively, whereas the corresponding figures for black men were 0.82, 0.90 and 0.76 years, respectively. Although the impact of the elimination of the other causes remained relatively stable from 1987 to 1992, the potential gains in life expectancy for black men of working age by eliminating HIV/AIDS rose from 0.36 years in 1987 to 0.82 years in 1992. For the total US population of working age, the elimination of HIV/AIDS deaths resulted in increased life expectancy similar to that observed for a 50% reduction of heart disease or malignant neoplasms, whereas among black men of working age, the increased years of life expectancy from the elimination of HIV/AIDS deaths were virtually the same as those observed for the elimination of heart disease or malignant neoplasms. CONCLUSIONS: The potential gains in life expectancy by reduction of deaths from heart disease and malignant neoplasms are more heavily influenced by increasing years after the working ages (15-64 years), whereas the potential gains in life expectancy by reducing deaths from HIV/AIDS make a greater contribution to those of working age. Hence, in terms of the economic costs and benefits, these results indicate that in evaluating policy issues regarding allocation of research funds, studies of life expectancy are far more important than the simple approach which allocates funds on the basis of the number of deaths due to various diseases.

Acquired Immunodeficiency Syndrome↗
PubMed1996

Neural cell type-specific expression of QKI proteins is altered in quakingviable mutant mice.

qkI, a newly cloned gene lying immediately proximal to the deletion in the quakingviable mutation, is transcribed into three messages of 5, 6, and 7 kb. Antibodies raised to the unique carboxy peptides of the resulting QKI proteins reveal that, in the nervous system, all three QKI proteins are expressed strongly in myelin-forming cells and also in astrocytes. Interestingly, individual isoforms show distinct intracellular distributions: QKI-6 and QKI-7 are localized to perikaryal cytoplasm, whereas QKI-5 invariably is restricted to the nucleus, consistent with the predicted role of QKI as an RNA-binding protein. In quakingviable mutants, which display severe dysmyelination, QKI-6 and QKI-7 are absent exclusively from myelin-forming cells. By contrast, QKI-5 is absent only in oligodendrocytes of severely affected tracts. These observations implicate QKI proteins as regulators of myelination and reveal key insights into the mechanisms of dysmyelination in the quakingviable mutant.

Aging↗
PubMed1996

Cytoplasmic and nuclear localization of myelin basic proteins reveals heterogeneity among oligodendrocytes.

Myelin basic proteins (MBPs) are major proteins of central nervous system (CNS) myelin, where they facilitate the apposition of cytoplasmic faces of myelin lamellae. Myelin-bearing oligodendrocytes transport MBP mRNA to myelin, where newly translated protein is directly inserted into the myelin sheath. An apparent absence of MBPs in oligodendrocyte perikarya has suggested that MBP localized to the soma is translationally inert. We now demonstrate by confocal immunofluorescence microscopy that not only are MBPs present in the majority of oligodendrocyte perikarya but oligodendrocytes are heterogeneous with respect to their localization of MBPs; MBPs are concentrated in some cells at the plasmalemma and distributed in others throughout the cytoplasm and, surprisingly, the nucleus. MBPs are present in the nuclei of over half of oligodendrocytes in the adult, but in almost all MBP+oligodendrocytes during myelinogenesis. Transport of MBPs into nuclei appears to be a regulated process since some cells exhibit robust MBP accumulation in their cytoplasm but exclude MBPs from their nuclei. We show that oligodendrocyte nuclei contain all four major MBP isoforms, but that in transgenic mice, the epitope-tagged 14 kD MBP isoform preferentially segregates to the plasmalemma. Our data demonstrate that oligodendrocytes are not required to exclude MBPs from their perikarya and suggest that MBPs have a specific function in the oligodendrocyte perikarya and nucleus.

Animals↗
PubMed1996

Statistical analysis of the standardized mortality ratio and life expectancy.

A new theoretical relation that does not require the constant age-specific mortality ratio assumption is established between the standardized mortality ratio (SMR) and the life expectancy. A set of regression equations is developed from the theoretical relation to derive estimates of the future expectation of life from estimates of the SMR. Curves are presented showing the changes in life expectancy that are associated with a given SMR for individuals aged 25, 45, and 65 years. These results will provide practical applications in estimating remaining life expectancy in epidemiologic studies in which the SMR is the summary statistic. An application is shown for studies in occupational health to develop and illustrate the method.

Adult↗
PubMed1996

A likelihood approach to meta-analysis with random effects.

In a meta-analysis of a set of clinical trials, a crucial but problematic component is providing an estimate and confidence interval for the overall treatment effect theta. Since in the presence of heterogeneity a fixed effect approach yields an artificially narrow confidence interval for theta, the random effects method of DerSimonian and Laird, which incorporates a moment estimator of the between-trial components of variance sigma B2, has been advocated. With the additional distributional assumptions of normality, a confidence interval for theta may be obtained. However, this method does not provide a confidence interval for sigma B2, nor a confidence interval for theta which takes account of the fact that sigma B2 has to be estimated from the data. We show how a likelihood based method can be used to overcome these problems, and use profile likelihoods to construct likelihood based confidence intervals. This approach yields an appropriately widened confidence interval compared with the standard random effects method. Examples of application to a published meta-analysis and a multicentre clinical trial are discussed. It is concluded that likelihood based methods are preferred to the standard method in undertaking random effects meta-analysis when the value of sigma B2 has an important effect on the overall estimated treatment effect.

Antihypertensive Agents↗
PubMed1996

Partial retinal detachment at 3 months after threshold retinopathy of prematurity. Long-term structural and functional outcome. Multicenter Trial of Cryotherapy for Retinopathy of Prematurity Cooperative Group.

OBJECTIVE: To investigate the structural and functional outcome at age 4 1/2 years of eyes that had partial retinal detachment (RD) at 3 months after the occurrence of threshold retinopathy of prematurity; these eyes were involved in the Multicenter Trial of Cryotherapy for Retinopathy of Prematurity study. METHODS: Of the 531 eyes in the randomized portion of the Multicenter Trial of Cryotherapy for Retinopathy of Prematurity study, 61 had partial RD at the 3-month examination. The extent of retinal involvement was recorded, and the presence of a foveal detachment was noted. At the examination conducted at age 4 1/2 years, the fundus structure was graded into cicatricial retinopathy of prematurity outcome categories by study ophthalmologists, and the visual acuity was measured by masked examiners using the Teller Acuity Card procedure and the crowded HOTV recognition acuity test. RESULTS: Of the 61 eyes, 7 eyes continued to have partial RD at age 4 1/2 years. Of the remaining eyes, 20 eyes had structural outcomes classified as favorable in the Multicenter Trial of Cryotherapy for Retinopathy of Prematurity study, and 27 eyes had unfavorable structural outcomes. Data were unrecordable for 3 eyes and missing for 4 eyes. No difference in outcome was found for eyes with partial RD at 3 months that had undergone cryotherapy vs eyes that had served as controls. Only 6 eyes had a visual acuity better than 20/200. When partial RDs did not involve the fovea at 3 months, structural and functional outcomes at 4 1/2 years were better than when RDs involved the fovea. The best predictor of outcome was the extent of RD at 3 months. CONCLUSIONS: Partial RD present 3 months after threshold retinopathy of prematurity is unstable anatomically, and the visual outcome is generally poor. Structure and function at 4 1/2 years are related to the extent of RD and the involvement of the fovea at 3 months.

Child, Preschool↗
PubMed1996

Visual fields measured with double-arc perimetry in eyes with threshold retinopathy of prematurity from the cryotherapy for retinopathy of prematurity trial. The CRYO-Retinopathy of Prematurity Cooperative Group.

PURPOSE: To measure monocular visual field extent in very-low birth weight children in whom severe (threshold) acute-phase retinopathy of prematurity (ROP) developed in one or both eyes, and who had random assignment of eyes to cryotherapy or no cryotherapy. A control group of very-low birth weight children in whom ROP did not develop also was tested. METHODS: There were 78 children in the severe ROP group from 5 of 23 centers in the randomized trial of cryotherapy for ROP (CRYO-ROP). The comparison cohort consisted of 75 study participants in whom ROP did not develop. All subjects had birth weights of less than 1251 g. At the 5 1/2-year study examination, visual field size was measured using double-arc kinetic perimetry. Testers were masked to treatment status of each eye. Four meridia were tested: superotemporal (ST), inferotemporal (IT), inferonasal (IN), and superonasal (SN). Target size was 6 degrees. RESULTS: When blind eyes were assigned a score of 0 degree, the no-ROP, treated, and control eyes had an average visual field extent of 62 degrees, 35 degrees, 27 degrees at ST; 73 degrees, 42 degrees, 35 degrees at IT; 51 degrees, 30 degrees, 21 degrees IN; and 50 degrees, 26 degrees, 22 degrees at SN, respectively. Among 25 children who had bilateral threshold ROP and measurable fields in each eye, values for treated and control eyes were 59 versus 62 at ST, 69 versus 80 at IT, 44 versus 49 at IN, and 41 versus 48 at SN, respectively. CONCLUSIONS: Overall, visual fields in eyes that reached threshold ROP were smaller than those of eyes that did not develop ROP. When only pairs of sighted eyes were considered, visual fields in the treated eyes were 6.4 degrees smaller than those of control eyes. Therefore, it appears that a small loss of peripheral field occurs when cryotherapy prevents the development of retinal detachment.

Child, Preschool↗
PubMed1996

Progressive remodeling of the oligodendrocyte process arbor during myelinogenesis.

Myelin sheaths develop in the central nervous system (CNS) as elaborations of the processes of oligodendrocytes. Although many details of the spiral wrapping of oligodendrocyte processes around axons and their subsequent transformation into myelin sheaths are known from thin-section electron-microscopic studies, the three-dimensional architecture of the myelin-forming cells is incompletely understood. To characterize this aspect of oligodendrocyte development, we labeled thick (100- to 300-microns) sections of developing murine CNS with oligodendrocyte marker antibodies, recorded individual cells in serial optical sections by confocal microscopy, and created whole-cell reconstructions of oligodendrocytes before and during the initiation of myelination. We distinguish three stages in the maturation of oligodendrocytes, which at all three stages are labeled by the O4, O1 and Ranscht monoclonals and by antibodies against the myelin-specific proteins CNP and myelin basic protein. Premyelinating oligodendrocytes, present before axonal ensheathment begins, emit multiple irregular processes which have predominant radial orientation. These processes, which generally terminate within 50 microns of the cell body, have a surface area 3-8 times or more that of the cell body itself and may represent a mechanism for sampling the local environment of each cell and for identifying target axons. Transitional cells have initiated one or more myelin sheaths; these cells progressively reduce the number of their radial processes as they increase the number of their myelin internodes. The radial processes of each transitional cell are most reduced in parts of the process arbor where ensheathment has begun, suggesting directional control in the elaboration or stability of the radial processes. Mature myelin-bearing oligodendrocytes entirely lack the radial processes and instead emit a few sparsely branching processes which connect cell bodies with myelin internodes. Three-dimensional analysis of the earliest stages in myelin sheath formation reveals two distinct phases. The initiating event in the formation of myelin internodes is the growth of thin unbranched processes, termed 'initiator processes', along axons. The second phase, spiral ensheathment of target axons, begins through the elaboration from each initiator process of lamellar extensions which extend circumferentially around the target axon and thereby form the first turn of its myelin sheath.

Animals↗
PubMed1996

Oligodendrocyte progenitors are generated throughout the embryonic mouse brain, but differentiate in restricted foci.

Recent evidence from studies mapping the expression of putative oligodendrocyte progenitor specific mRNAs has suggested that oligodendrocyte progenitors arise during embryogenesis, in specific foci of the neuroectoderm. In order to test this hypothesis, we have assayed different regions of the embryonic central nervous system for their ability to generate oligodendrocytes following transplantation into neonatal cerebrum. To allow identification of donor-derived oligodendrocytes in wild-type host brain, we used the MbetaP transgenic mouse, which expresses lacZ in oligodendrocytes, as donor tissue. We found that tissue fragments derived from several levels of the anterior-posterior axis of the neural tube at E14.5 and E12.5, chosen to include (hindbrain, cervical and lumbar spinal cord), or exclude (dorsal telencephalon) putative foci of oligodendrocyte progenitors, all produced oligodendrocytes following transplantation. In addition, these same regions taken from E10.5, prior to the appearance of putative oligodendrocyte progenitor markers, also all yielded oligodendrocytes on transplantation. This indicates that precursor cells that can generate oligodendrocytes are widespread throughout the neuroectoderm as early as E10.5. We have also used the oligodendrocyte lineage-specific glycolipid antibodies O4, R-mAb and O1 to identify those regions of the developing brain that first support the differentiation of oligodendrocytes from their progenitor cells. We found that the first oligodendrocytes arise in prenatal brain at E14.5, in a restricted zone adjacent to the midline of the medulla. These cells are mitotically inactive, differentiated oligodendrocytes and, using light and electron microscopy, we show that they become functional, myelin-bearing oligodendrocytes. We have mapped the subsequent appearance of differentiated oligodendrocytes in the prenatal brain and show that they appear in a restricted, tract-specific manner. Our results suggest that oligodendrocytes are generated from neuroectodermal cells positioned throughout the rostrocaudal axis of the neural tube, rather than at restricted locations of the neuroectoderm. By contrast, the differentiation of such cells into oligodendrocytes does occur in a restricted manner, consistent with local regulation of oligodendrocyte progenitor differentiation.

Animals↗
PubMed1996

Color vision measured with pseudoisochromatic plates at five-and-a-half years in eyes of children from the CRYO-ROP study.

PURPOSE: To investigate the prevalence of color deficits at age 5 1/2 years in preterm children with birth weights of less than 1251 g who participated in the multicenter Cryotherapy for Retinopathy of Prematurity (CRYO-ROP) study. METHODS: Two cohorts of CRYO-ROP participants served as subjects: 1055 children who participated in a long-term study of the natural history of ROP at 5 of the 23 CRYO-ROP centers, and 187 children (from all 23 study centers) who had threshold ROP in both eyes and who were randomized to receive cryotherapy in 1 eye. Monocular color vision was tested at age 5 1/2 years, using the Standard Pseudoisochromatic Plates, part 2 (SPP2) for acquired color vision defects. RESULTS: In the Natural History cohort, prevalence of red-green (R-G) color deficits was 6.6% for males and 1.0% for females, similar to that of the general adult population. Prevalence of blue-yellow (B-Y) color deficits was 2.8% for males and 2.2% for females, more than 200 times that in the general adult population. Prevalence of B-Y deficits was not related to birth weight, gestational age, acute-phase ROP, optic atrophy, or retinal residua of ROP, but was related to visual acuity. In the Threshold ROP cohort, color vision deficits were no more likely in eyes that had received cryotherapy than in control eyes. CONCLUSIONS: The results confirm an increased prevalence of B-Y deficits in children born before term, and provide evidence that the increased prevalence is not related to birth weight, gestational age, or severity of ROP within this group of preterm children. No evidence was found to indicate that cryotherapy increased the rate of color vision deficits in eyes with threshold ROP.

Birth Weight↗
PubMed1995

Correlation of retinopathy of prematurity in fellow eyes in the cryotherapy for retinopathy of prematurity study. The Cryotherapy for Retinopathy of Prematurity Cooperative Group.

OBJECTIVE: To examine the similarity of extent (sectors) and severity (stage) of acute-phase retinopathy of prematurity (ROP) between fellow eyes and the concordance of cicatricial outcomes at age 1 year of eyes that did not develop threshold disease. METHODS: Four thousand ninety-nine infants with birth weights of less than 1251 g who participated in a natural history segment of the Cryotherapy for Retinopathy study underwent biweekly eye examinations from 4 to 6 weeks after birth until retinal vasculature was complete or until ROP regressed or reached threshold severity. Eyes were categorized as follows: (1) no ROP, (2) less than prethreshold ROP, (3) prethreshold ROP, (4) threshold ROP, and (5) unable to determine. The presence and stage of ROP residua in fellow eyes were evaluated at 12 months. RESULTS: Acute-phase ROP status between 32 and 42 weeks postconceptional age showed a high degree of correspondence between fellow eyes in severity (stage) and location (zone) of ROP, presence of plus disease, and sectors of stage 3 retinopathy. More variability between eyes was seen when cicatricial status at age 1 year was examined. This higher variability was evident even though results from patients with threshold ROP (many of whom underwent cryotherapy) were excluded. CONCLUSION: The usual course of ROP during its acute phase is for fellow eyes to be very similar in ROP status. However, asymmetry between eyes is not unusual in eyes with posterior pole residua of ROP.

Acute Disease↗
PubMed1994

Data monitoring in clinical trials: the case for stochastic curtailment.

Interim analyses have become an essential part of the monitoring process of clinical trials. Stochastic curtailment has been used in such analyses. This procedure allows for calculation of the probability of rejecting the null hypothesis at the end of a trial given the current data and assuming the null or an alternative hypothesis for the remainder of the trial. Such information can be used to decide whether a trial should continue or be stopped early due to either treatment benefit or harm or because of lack of power to show an effect. Using stochastic curtailment, stopping rules for one- or two-sided test trials can be easily visualized by constructing boundaries based on the null and alternative hypotheses. Interim Z test statistics falling above or below these boundaries can aid in interim monitoring decisions. Methods for constructing boundaries, expected trial times and examples of clinical trials in cardiovascular and vision research where stochastic curtailment was used are presented.

Clinical Trials as Topic↗
PubMed1993

Surfactant prophylaxis and retinopathy of prematurity.

OBJECTIVE: The use of exogenous surfactant has led to a decrease in mortality of low-birth-weight infants. In some instances, use of this drug has also led to a reduction in neonatal morbidity, such as respiratory distress syndrome. This study was undertaken to determine whether prophylactic surfactant therapy has an effect on the incidence and severity of retinopathy of prematurity. DESIGN: The authors reviewed the findings of sequential prospective ophthalmologic examinations performed in two neonatal intensive care units that participated in randomized trials of prophylactic exogenous mammalian surfactant. PATIENTS: There were 43 patients in the control group (no prophylactic surfactant) and 43 patients in the prophylactic surfactant group. These groups did not differ on the basis of birth weight, gestational age, race, or gender. RESULTS: The incidence and severity of retinopathy of prematurity did not vary between the control and surfactant-treated infants. Only birth weight appeared to be significantly related to the incidence and severity of retinopathy of prematurity. CONCLUSIONS: These results suggest that the widespread use of prophylactic surfactant therapy will not change the incidence of retinopathy of prematurity in extremely low-birth-weight infants. However, the absolute number of affected patients will likely increase because of the decrease in mortality of extremely low-birth-weight patients, the patients most at risk for retinopathy of prematurity.

Female↗
PubMed1993

Prognostic factors in the natural course of retinopathy of prematurity. The Cryotherapy for Retinopathy of Prematurity Cooperative Group.

BACKGROUND: There exists no reliable information that allows the ophthalmologist to predict with any degree of certainty a particular infant's chances of requiring surgical treatment for retinopathy of prematurity (ROP) or of reaching an unfavorable outcome on the basis of the retinal findings at the time of the nursery examination. METHODS: In the Multicenter Trial of Cryotherapy for Retinopathy of Prematurity (CRYO-ROP), 4099 infants weighing less than 1251 g at birth underwent eye examinations that began at 4 to 6 weeks after birth and subsequently continued at 2-week intervals. Independent variables in the population were studied using multiple logistic regressions. RESULTS: An increased risk of reaching threshold ROP was found associated with lower birth weights, younger gestational age, white race, multiple birth, and being born outside a study center nursery. For infants who developed ROP (66%), corresponding probabilities are presented for developing severe ("threshold") ROP or of having an unfavorable macular outcome. The risk of an unfavorable macular outcome was increased with zone 1 ROP, "plus" disease, the severity of the stage, and the amount of circumferential involvement. A higher risk also was associated with a rapid rate of progression of ROP to prethreshold disease but not with the postconceptional age at which ROP was first noted. CONCLUSION: The findings indicate that the ocular characteristics of ROP, along with some easily identifiable and available basic systemic and demographic information about an infant, can assist the ophthalmologist in understanding variations in an individual baby's chance for a good or poor macular outcome.

Child, Preschool↗
PubMed1992

The standardized mortality ratio and life expectancy.

This paper develops a theoretical relation between the standardized mortality ratio (SMR) and the expected years of life and establishes a regression equation for easy conversion between these two statistics. The mathematical expression of the derived relation is an approximation, requiring an assumption of constant age-specific mortality ratios. It underestimates the "true" value calculated based on life table technique when the age-specific mortality ratios increase with age. This equation provides a conservative method to estimate the expected years of life for cohort mortality studies and facilitates an assessment of the impact of work-related factors on the length of life of the worker. It also allows one to convert the SMR to life expectancy in smaller studies whose sole objective is to determine the SMR in a working population. A 1% decrease (or increase) in the standardized mortality ratio will result in 0.1373 years increased (or decreased) life expectancy based on white male data for the US population. Furthermore, with data from 14 large oil refinery and chemical worker cohorts of white males, the "derived" expected years of life based on the regression equation closely predicts the corresponding value calculated using a standard life table technique. This statistical equation is expected to have practical applications when used in conjunction with the SMR to provide an approximate measure of life expectancy, a term and statistic familiar to most lay people.

Adult↗
PubMed1992

Combined simian hemorrhagic fever and Ebola virus infection in cynomolgus monkeys.

Simian hemorrhagic fever (SHF) virus and a new strain of Ebola virus were isolated concurrently in recently imported cynomolgus monkeys (Macaca fascicularis) being maintained in a quarantine facility. Ebola virus had never been isolated in the U.S. previously and was presumed to be highly pathogenic for humans. A chronology of events including measures taken to address the public health concerns is presented. The clinicopathologic features of the disease were abrupt anorexia, splenomegaly, marked elevations of lactate dehydrogenase, alanine aminotransferase, and aspartate aminotransferase, with less prominent elevations of blood urea nitrogen, creatinine, and other serum chemistry parameters. Histologically, fibrin deposition, hemorrhage, and necrosis of lymphoid cells and reticular mononuclear phagocytes were present in the spleens of SHF and of Ebola virus-infected animals. Intravascular fibrin thrombi and hemorrhage were also present in the renal medulla and multifocally in the gastrointestinal tract. Necrosis of lymphoid and epithelial cells was occasionally noted in the gastrointestinal tract. The histopathologic findings considered specific for Ebola virus infection include hepatocellular necrosis, necrosis of the zona glomerulosa of the adrenal cortex, and interstitial pneumonia, all of which were generally associated with the presence of 1 to 4 mu intracytoplasmic amphophilic inclusion bodies. The disease spread within rooms despite discontinuation of all direct contact with animals, and droplet or aerosol transmission was suspected. Antibody to Ebola virus developed in animal handlers but no clinical disease was noted, suggesting a less virulent strain of virus.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Genetic epidemiology of childhood brain tumors.

The study goal was to determine the genetic (heritable) contribution to childhood brain tumors (CBT) which cause nearly one quarter of all childhood cancer deaths. Their etiology remains unknown, but previous studies have suggested a proportion of CBT may be heritable. In this study we collected family histories of 243 confirmed CBT patients referred to The University of Texas M. D. Anderson Cancer Center between the years 1944 and 1983, diagnosed before age 15, and residents of the United States or Canada. Family histories were obtained for all the probands' first degree relatives (parents, siblings, and offspring) and extended to include selected second degree relatives (aunts, uncles, grandparents) using sequential sampling. To determine if these CBT families exhibited excess cancer, we compared their cancer experience to age-, race-, sex-, and calendar-year specific rates from the Connecticut Tumor Registry. No cancer excess was observed among 1,099 first and second degree relatives [39 cancers observed (O) and 44 expected (E) for a standardized incidence ratio (SIR) of 0.88]. For colon cancer, although small numbers, five cases were observed among the probands' first degree relatives with 1.6 expected, for a significant SIR of 3.10. Segregation analysis demonstrated that chance alone could not account for the observed cancer distribution with a multifactorial model providing the best overall explanation of the data. Overall, heredity played a role in the etiology of CBT in 4% of the study families: four (1.7%) due to known hereditary syndromes (nevoid basal cell carcinoma syndrome and von Recklinghausens neurofibromatosis--NF-1), four (1.7%) with multifactorial inheritance, and two additional families with cancers aggregating similar to the clinical criteria described for the Li-Fraumeni cancer family syndrome.

Adolescent↗