Are the UK oncology trainees adequately informed about the needs of older people with cancer?

BACKGROUND: Outcomes for older people with cancer are poorer in the United Kingdom compared with that in other countries. Despite this, the UK oncology curricula do not have dedicated geriatric oncology learning objectives. This cross-sectional study of UK medical oncology trainees investigates the training, confidence level and attitudes towards treating older people with cancer. METHODS: A web-based survey link was sent to the delegates of a national medical oncology trainee meeting. Responses were collected in October 2011. RESULTS: The response rate was 93% (64 out of 69). The mean age of the respondents was 32.3 years (range 27-42 years) and 64.1% were female. A total of 66.1% of the respondents reported never receiving training on the particular needs of older people with cancer, 19.4% reported to have received this training only once. Only 27.1% of the trainees were confident in assessing risk to make treatment recommendations for older patients compared with 81.4% being confident to treat younger patients. Even fewer were confident with older patients with dementia (10.2%). CONCLUSION: This first study of the UK medical oncology trainees highlights the urgent need for change in curricula to address the complex needs of older people with cancer.

History of aromatase: saga of an important biological mediator and therapeutic target.

Aromatase is the enzyme that catalyzes the conversion of androgens to estrogens. Initial studies of its enzymatic activity and function took place in an environment focused on estrogen as a component of the birth control pill. At an early stage, investigators recognized that inhibition of this enzyme could have major practical applications for treatment of hormone-dependent breast cancer, alterations of ovarian and endometrial function, and treatment of benign disorders such as gynecomastia. Two general approaches ultimately led to the development of potent and selective aromatase inhibitors. One targeted the enzyme using analogs of natural steroidal substrates to work out the relationships between structure and function. The other approach initially sought to block adrenal function as a treatment for breast cancer but led to the serendipitous finding that a nonsteroidal P450 steroidogenesis inhibitor, aminoglutethimide, served as a potent but nonselective aromatase inhibitor. Proof of the therapeutic concept of aromatase inhibition involved a variety of studies with aminoglutethimide and the selective steroidal inhibitor, formestane. The requirement for even more potent and selective inhibitors led to intensive molecular studies to identify the structure of aromatase, to development of high-sensitivity estrogen assays, and to "mega" clinical trials of the third-generation aromatase inhibitors, letrozole, anastrozole, and exemestane, which are now in clinical use in breast cancer. During these studies, unexpected findings led investigators to appreciate the important role of estrogens in males as well as in females and in multiple organs, particularly the bone and brain. These studies identified the important regulatory properties of aromatase acting in an autocrine, paracrine, intracrine, neurocrine, and juxtacrine fashion and the organ-specific enhancers and promoters controlling its transcription. The saga of these studies of aromatase and the ultimate utilization of inhibitors as highly effective treatments of breast cancer and for use in reproductive disorders serves as the basis for this first Endocrine Reviews history manuscript.

Inhibition of post-meningitic cochlear injury with cerebrospinal fluid irrigation.

OBJECTIVE: Labyrinthitis ossificans, the pathologic ossification of the otic capsule associated with profound deafness and loss of vestibular function occurs frequently as a sequella of bacterial meningitis and subsequent purulent labyrinthitis. Experimentally, in Streptococcus pneumoniae meningitis, it has been shown that a vigorous inflammatory response to teichoic acids in the bacterial cell wall contributes to cochlear damage and subsequent fibrosis and ossification. The hypothesis of this study is that a dilution of concentration of inflammatory mediators through cerebrospinal fluid (CSF) irrigation will lead to a reduction in both inner ear pathology and permanent hearing loss. STUDY DESIGN AND SETTING: Auditory brainstem response testing was used to determine baseline hearing thresholds in 20 Mongolian gerbils (12 irrigated, 8 sham irrigated animals) at 32 kHz, 16 kHz, 8 kHz, and 4 kHz frequencies. Their thresholds at 14 days and 120 days post-procedure were also obtained. Streptococcus pneumoniae meningitis was induced in both groups of animals by intrathecal (i.t.) injection of bacteria. Both groups received penicillin treatment. Forty-eight hours after inoculation, both groups were implanted with i.t. inflow and outflow catheters. The irrigated group was infused continuously with artificial CSF over 36 hr at a rate of 70 muL/hr and the outflow sampled. The tubing in the sham irrigated group was clamped (without sampling). They were sacrificed at 120 days post-procedure and histomorphometric analysis carried out. The concentration of interleukin 1beta (IL-1beta) for the CSF samples from the irrigated group were compared to samples collected from an additional control group of 8 non-irrigated meningitic gerbils. IL-1beta was chosen to study because it is a potent pro-inflammatory cytokines in bacterial meningitis that is unaffected by the neurosurgical trauma of the experimental protocol. RESULTS: Twenty animals survived the meningitis (6 irrigation, 6 sham irrigation, 8 non-irrigation meningitic controls). At Days 14 and 120 post-infection, the irrigated animals manifested significantly less hearing loss with a mean loss of 28.82 dB compared to the sham irrigation group mean loss of 40.76 dB (P < 0.03). The degree of hearing loss in both groups was frequency-dependent with greater loss at higher frequencies (mean loss = 22.4 dB at 32 kHz, 23.0 dB at 16 kHz, 18.6 dB at 8 kHz, and 12.5 dB at 4 kHz). Histomorphometric analysis demonstrated a marked reduction in degeneration of the spiral ligament, spiral ganglion cells, and stria vascularis in experimental animals as compared to controls. Immunohistochemistry showed a significant reduction in IL-beta1 concentrations in the irrigated animals compared to the non-irrigated, infected controls (P < 0.03). CONCLUSIONS: Irrigation of CSF resulted in a significant reduction in post-meningitic cochlear injury when compared to controls. This model for continuous cerebrospinal fluid irrigation provides a means to evaluate the effects of a dilution of inflammatory mediators on hearing loss and labyrinthitis ossificans after bacterial meningitis. SIGNIFICANCE: Despite advances in the prevention of meningitis and improved antibiotic treatment, bacterial meningitis continues to have significant associated morbidity. This study provides insight into some of the mechanisms responsible for post-meningitic hearing loss and labyrinthitis ossificans and presents a novel approach to reduce these complications.

Choristoma of the middle ear: a component of a new syndrome?

CASE REPORT: Salivary choristoma of the middle ear is a rare entity. The authors report the 26th known case, which is unique in several respects: the patient had abnormalities of the first and second branchial arches, as well as the otic capsule and facial nerve in ways not yet reported. Our patient presented with bilateral preauricular pits, conchal bands, an ipsilateral facial palsy, and bilateral Mondini-type deformities. A review of the literature revealed salivary choristomas of the middle ear to be frequently associated with branchial arch abnormalities, most commonly the second, as well as abnormalities of the facial nerve. REVIEW OF THE LITERATURE: All 25 cases were reviewed and the results reported with respect to clinical presentation, associated abnormalities, operative findings, and hearing results. It has been proposed that choristoma of the middle ear may represent a component of a syndrome along with unilateral hearing loss, abnormalities of the incus and/or stapes, and anomalies of the facial nerve. CONCLUSION: Eighty-six percent of the reported patients with choristoma have three or four of the four criteria listed to designate middle ear salivary choristoma as part of a syndrome. In the remaining four patients, all of the structures were not assessed.

MR, CT, and plain film imaging of the developing skull base in fetal specimens.

BACKGROUND AND PURPOSE: The developing fetal skull base has previously been studied via dissection and low-resolution CT. Most of the central skull base develops from endochondral ossification through an intermediary chondrocranium. We traced the development of the normal fetal skull base by using plain radiography, MR imaging, and CT. METHODS: Twenty-nine formalin-fixed fetal specimens ranging from 9 to 24 weeks' gestational age were examined with mammographic plain radiography, CT, and MR imaging. Skull base development and ossification were assessed. RESULTS: The postsphenoid cartilages enclose the pituitary and fuse to form the basisphenoid, from which the sella turcica and the posterior body of the sphenoid bone originate. The presphenoid cartilages will form the anterior body of the sphenoid bone. Portions of the presphenoid cartilage give rise to the mesethmoid cartilage, which forms the central portion of the anterior skull base. Ossification begins in the occipital bone (12 weeks) and progresses anteriorly. The postsphenoid (14 weeks) and then the presphenoid portion (17 weeks) of the sphenoid bone ossify. Ossification is seen laterally (16 weeks) in the orbitosphenoid, which contributes to the lesser wing of the sphenoid, and the alisphenoid (15 weeks), which forms the greater wing. CONCLUSION: MR imaging can show early progressive ossification of the cartilaginous skull base and its relation to intracranial structures. The study of fetal developmental anatomy may lead to a better understanding of abnormalities of the skull base.

Nursing assistants detect behavior changes in nursing home residents that precede acute illness: development and validation of an illness warning instrument.

BACKGROUND: Acute illness causes considerable morbidity and mortality in nursing home residents but is often difficult to recognize early. Nursing assistants often notice early signs of acute illness but do not methodically document or communicate their observations with medical staff. OBJECTIVE: To enhance nursing assistants' observation and documentation of signs of acute illness by developing a validated, standardized instrument for communication with medical staff. DESIGN: Observational cohort study. SETTING: Urban not-for-profit nursing home. SUBJECTS AND METHODS: Candidate instrument items were generated in focus group interviews with nursing home staff. Twenty-three nursing assistants completed the instrument on 74 nursing home residents over 4 weeks. Acute illness, the primary outcome, was identified by nurse report and chart review and determined according to preset criteria. MEASUREMENTS: Predictive validity was assessed by determining the relationship between instrument responses and development of acute illness within 7 days. Interobserver agreement was calculated between morning and afternoon nursing assistants' responses. Convergent validity was assessed by comparing instrument responses with three standard status indicators. RESULTS: The instrument consisted of 12 items that assessed behavioral and functional status changes. Residents with an instrument-recorded change were more likely to develop an acute illness within 7 days than those with no change (risk ratio 4.1, 95% confidence interval 2.6, 6.3). A final five-item instrument had a sensitivity of 53% and a specificity of 93% for acute illness. Nursing assistants' documentation of signs of illness preceded chart documentation by an average of 5 days. Interobserver agreement between morning and afternoon nursing assistants was 76%. Correlation of responses with standard indicators of functional, mental, and global status was high. CONCLUSIONS: A new instrument developed for nursing assistants to document behavioral and functional status changes in nursing home residents demonstrates fair sensitivity and high specificity for acute illness. Close monitoring of patients with a positive instrument might avert morbidity and mortality from acute illness by allowing earlier treatment.

Effects of depletion of complement in the development of labyrinthitis ossificans.

HYPOTHESIS: Labyrinthitis ossificans results in part from the intense inflammatory response to Streptococcus pneumoniae cell wall components. Depletion of complement in Mongolian gerbils following induction of meningitis will reduce the degree of inflammation and subsequent cochlear fibrosis. STUDY DESIGN: Random prospective study. Histological evaluations were performed with the researcher blinded to the experimental group METHODS: S. pneumoniae meningitis was induced in 10 control and 18 experimental Mongolian gerbils with an intrathecal injection of the bacteria. Both groups of animals received treatment with penicillin. The experimental group was also treated with cobra venom factor to deplete complement in the animals. Three months after the induction of meningitis, the animals' temporal bones were harvested for histological evaluation. RESULTS: The decomplemented animals developed significantly less intracochlear fibrosis (P < .01). The mortality rate for the experimental group was 11% compared with 40% in the control group (P = .14). CONCLUSIONS: Reduction of the intense inflammatory response to the S. pneumoniae cell wall components in suppurative labyrinthitis secondary to bacterial meningitis reduced the degree of labyrinthitis ossificans.

The efficacy of perioperative steroid therapy in pediatric primary palatoplasty.

OBJECTIVE: To determine if perioperative steroid therapy benefits pediatric primary palatoplasty patients. DESIGN: A prospective, double-blind, randomized trial with a placebo control. SETTING: An academic medical center. PATIENTS: Forty-five children undergoing primary repair of their cleft palate between 1989 and 1996 who were under the age of 48 months and without developmental delay or any associated syndrome. INTERVENTIONS: Intravenous dexamethasone sodium phosphate (0.25 mg/kg) or a placebo (5% dextrose in water) immediately preoperatively and once every 8 hours for two doses postoperatively. MAIN OUTCOME MEASURES: Postoperative airway distress, fever, oral fluid intake, discharge eligibility, and palatal fistula formation. RESULTS: Perioperative steroid therapy significantly reduced the incidence of postoperative airway distress (p = .05) and postoperative fever (p = .02); postoperative oral fluid intake, discharge eligibility, and palatal fistula formation were not significantly affected. CONCLUSIONS: Perioperative steroids effectively lower the risk of postoperative airway distress and postoperative fever in children undergoing the primary repair of their cleft palate. This finding favors a customary role for perioperative steroid therapy in pediatric primary palatoplasty.

Chronology of labyrinthitis ossificans induced by Streptococcus pneumoniae meningitis.

OBJECTIVE: Labyrinthitis ossificans consists of novel osteogenesis that fills the normally patent cochlear and vestibular lumen as an end-stage sequelae to various pathologies. This study was designed to establish the sequence of events and chronology of the osteoneogenesis and calcification. STUDY DESIGN: A prospective randomized double-blind study. METHODS: By using serial application of different colored fluorochromes, which deposit in newly forming bone, the timing of bone deposition and bone remodeling can be established. Labyrinthitis ossificans was induced in six groups (n = 5) of gerbils by an intrathecal injection of live Streptococcus pneumoniae. Group 1 received no fluorochrome labels, group 2 received one label, group 3 received three labels, and groups 4, 5, and 6 received four labels. The temporal bones were harvested after 2 weeks (group 1), 1 month (group 2), 3 months (group 3), 4 months (group 4), 6 months (group 5), and 12 months (group 6). RESULTS: Sixteen of the 25 animals that received labels developed ossification, demonstrated with fluorescent microscopy. In the animals that developed labyrinthitis ossificans, newly formed disorganized bone began calcifying as early as 3 weeks (label 1) after S. pneumoniae injection. Osteoneogenesis continued as evidenced by the presence of the other labels when first applied at 6 weeks (label 2), and 10 weeks (label 3). Ossification, calcification, and remodeling proceeded through a 12-month course, wherein a reduction of labels was present at 6 months and total disappearance by 12 months. CONCLUSIONS: The use of fluorescent stains in this animal model provides a means to establish a timeline of the ossification seen in labyrinthitis ossificans.

Anesthetic management of preeclampsia/eclampsia.

Preeclampsia/eclampsia affects only a small proportion of all pregnancies, yet accounts for much of the obstetric morbidity and mortality seen in the USA and UK. A full understanding of preeclampsia/eclampsia, its variable presentation and complex pathophysiology allows the consulting anesthesiologist to optimize a plan for anesthetic management of the afflicted patient.

Induction of labyrinthitis ossificans after pneumococcal meningitis: an animal model.

Newly formed disorganized bone fills the open spaces within the otic capsule in various pathologic conditions, resulting in labyrinthitis ossificans. The pathologic mechanisms of this disease remain poorly understood. To better study the sequence of events and contributing mechanisms involved in labyrinthitis ossificans, an animal model was developed. Three groups of Mongolian gerbils received either an intralabyrinthine injection of normal saline solution (group 1) or Streptococcus pneumoniae polysaccharide capsule antigens (groups 2 and 3). The temporal bones were harvested after 3 months and serially sectioned. None of the eight control animals (group 1), which received intralabyrinthine injections of normal saline solution had any histologic changes in their temporal bones. Nine of the surviving 19 animals in groups 2 and 3 had fibrosis or evidence of early ossification. A fourth group of Mongolian gerbils received two intrathecal injections of live S. pneumoniae organisms. The temporal bones were harvested after 3 months and serially sectioned. Fourteen of the surviving 15 animals had fibrosis or ossification or both. This animal model will provide a method for study of the mechanisms of labyrinthitis ossificans.

Removal of a cholesteatoma in a dog, using a caudal auricular approach.

A new surgical method for treating cholesteatoma in dogs is described. Although rarely reported in dogs, cholesteatomas may be more common than previously believed. Complete excision of a cholesteatoma is associated with low recurrence and good long-term prognosis. Surgical intervention, with total ear canal ablation and lateral bulla osteotomy, has been recommended in dogs with tumors of the middle ear; however, this technique often results in conductive hearing loss. Through a caudal auricular approach to the tympanic bulla, we were able to preserve the external ear canal, reconstruct the auditory ossicles, and graft the tympanic membrane. Results of brain stem auditory-evoked response tests in the dog revealed intact conduction potentials. A caudal auricular approach to the tympanic bulla is technically possible, preserves normal appearance, and may maintain, or even improve, hearing conduction of affected ears in dogs.

Prophylactic antibiotics for posttraumatic cerebrospinal fluid fistulae. A meta-analysis.

OBJECTIVE: To determine the efficacy of prophylactic antibiotics in the treatment of posttraumatic cerebrospinal fluid fistulae. DESIGN: Meta-analysis with literature review. METHODS: A MEDLINE search was performed to obtain all the reports pertaining to posttraumatic cerebrospinal fluid fistulae between 1970 and 1995. All the series that provided data specifying whether prophylactic antibiotics were provided and the incidence of the meningitis were included in the analysis. RESULTS: The findings of 6 studies, involving 324 patients, were analyzed. In these studies, 237 received prophylactic antibiotics and 87 did not. Only 6 of the 237 patients who received prophylactic antibiotics developed meningitis, yielding an incidence of 2.5%. Nine (10%) of the 87 patients who did not receive prophylactic antibiotics developed meningitis. The incidence of meningitis was significantly lower in the patients who received prophylactic antibiotics than in those who did not receive prophylaxis (Fisher exact test, P = .006). CONCLUSIONS: Individually, each of the studies included in this analysis demonstrated no significant difference in the incidence of meningitis with prophylactic antibiotic therapy. The reason for this is that inadequate numbers of patients were available at each institution. Pooling the data from the past 25 years revealed a statistically significant reduction in the incidence of meningitis with prophylactic antibiotic therapy.

Normatology: a review and commentary with reference to abortion and physician-assisted suicide.

PIP: This article opens with a review of the concept of "normatology," which was developed by Sabshin and Offer in four books published over a period of 30 years. Normatology seeks to produce an "operational definition of normality and health" over the life cycle. Such a definition can be used as a guideline in the deliver of health care. The importance of this field of study is highlighted when considering issues such as abortion or physician-assisted suicide. Fortunately, the proclivity of Americans to conduct public opinion polls helps researchers determine what is considered "normal" at any given time. Gallup Polls, which have posed the same question about the legality of abortion from 1975 to 1995, indicate that about half of all Americans continuously occupy the middle ground on this issue despite a somewhat liberalizing trend. In general, public opinion holds that it is normal to want to avoid giving birth to a damaged child, to place the mother's health and safety above that of the fetus, and to terminate a pregnancy resulting from rape. It is less normal to abort a healthy fetus on demand. Thus, abortion will likely continue to be a source of controversy and confusion in our society and among psychiatric patients. In comparison, psychiatrists express attitudes about abortion that are more liberal than normal. In the case of physician-assisted suicide, public approval has increased since 1950 as scientific advancements have facilitated the prolongation of unproductive and painful life. If legalized, physician-assisted suicide may depend upon psychiatric assessment of an absence of mental disease. Such an assessment is required in the Northern Territory of Australia, where voluntary euthanasia is legal, but not in the Netherlands, where it is government-regulated. Psychiatrists must understand public opinion in order to influence it or deal with it competently.^ieng

Management of complications from 820 temporal bone fractures.

OBJECTIVE: To review the incidence of complications resulting from temporal bone fractures and analyze the outcomes from surgical and nonsurgical management. STUDY DESIGN: A retrospective review of 699 patients with 820 temporal bone fractures occurring over a 5-year period. SETTING: A single level 1 trauma center. PATIENTS: All patients with clinical or radiologic evidence of a temporal bone fracture. RESULTS: A total of 820 fractured temporal bones resulted in 58 facial nerve injuries, 122 CSF fistulae, and 15 cases of meningitis. The two most important prognostic factors in recovery of facial paralysis were severity and delay of onset. All patients with incomplete paralysis recovered. All but one of the delayed onset palsies had good recovery of function. A total of 40% of patients with immediate onset complete paralysis had poor recovery of function. Ninety-five of the 122 CSF fistulae closed spontaneously within 1 week. CSF fistulae persisting for > 7 days had a significantly increased risk of developing meningitis (23%) compared with patients whose fistulae closed within 7 days (3%) (p = 0.001). Another important risk factor for the development of meningitis was concurrent infection. CONCLUSIONS: Facial function following temporal bone fractures should be evaluated in the emergency room. If facial motion is noted at any time after the injury, surgical intervention is rarely indicated. Prophylactic antibiotics should be considered in temporal bone fractures when CSF fistulae are present. Surgical closure of a CSF fistula is indicated if it persists for > 7-10 days.

Venous channels of the petrous apex: their presence and clinical importance.

A methyl methacrylate casting technique was used to make detailed casts of the intracerebral venous system of four human cadaver specimens. Seven of the eight petrous apices studied were diploeic (n = 5), or pneumatic (n = 2) and had venules coursing in the anterior petrous apex. These venules form conduits connecting the cavernous to the inferior petrosal sinus or the jugular bulb and have not been previously described. In addition to the air cell system of the petrous apex, these venules may represent pathways for the spread of infection and the development of petrous apicitis, Gradenigo's syndrome, and the rare otogenic cavernous sinus thrombophlebitis. Their presence also may help explain the location of cholesterol granulomas, which afflict this area of the skull base.

Imaging findings of the developing temporal bone in fetal specimens.

PURPOSE: To trace the development of the normal fetal temporal bone by means of plain radiography, MR, and CT. METHODS: Eighteen formalin-fixed fetal specimens, 13.5 to 24.4 weeks' gestational age, were examined with a mammographic plain film technique, CT, and MR imaging at 1.5 T. Temporal bone development and ossification were assessed. RESULTS: The membranous labyrinth grows with amazing rapidity and attains adult size by the middle of the gestation period. The cochlea, vestibule, and semicircular canals are very prominent and easily recognized on MR images. The otic capsule develops from a cartilage model. Ossification of the otic capsule proceeds rapidly between 18 and 24 weeks from multiple ossification centers that replace the cartilaginous framework. The mastoid, internal auditory canal, vestibular aqueduct, and external auditory canal continue to grow after birth. CONCLUSION: The study of fetal developmental anatomy may lead to a better understanding of congenital disorders of the ear. Faster MR scanning techniques may provide a method for in utero evaluation of the fetal temporal bone.

A prospective, double-blind, randomized study of the effects of perioperative steroids on palatoplasty patients.

OBJECTIVE: To determine whether perioperative steroids affect the outcome of patients who undergo palatoplasty. DESIGN: A prospective, double-blind, randomized study. SETTING: A university medical center. PATIENTS: Twenty patients undergoing primary repair of a cleft palate. INTERVENTION: A prospective double-blind technique was used to randomly assign patients to receive a placebo or dexamethasone sodium phosphate perioperatively. MAIN OUTCOME MEASURE: Patients were monitored for postoperative airway distress, fever, oral fluid intake, days of hospitalization, and wound healing. RESULTS: The use of perioperative steroids was associated with shorter hospitalizations. No adverse sequelae from the administration of steroids were identified. CONCLUSIONS: In our current managed care environment, the use of perioperative steroids may play an important role in reducing health care costs.

Dexamethasone inhibition of the development of dysplastic bony lesions in LP/J mice.

Inbred LP/J mice have been observed to spontaneously develop abnormal bony lesions of the ossicles and otic capsule that progress throughout the life of the animals. This genetically inherited murine disorder produces bony lesions that share some gross and histologic features with bony lesions seen in human tympanosclerosis. Previous studies on LP/J mice have demonstrated evidence of immunologically mediated injury in the progression of the newly forming bony lesions. This study was designed to examine the effects of dexamethasone on the development of the bony lesions in LP/J mice. The purpose was to attempt to elucidate the relationship of the immunologic injury observed in earlier studies and the progression of the dysplastic bony lesions. The results show that LP/J mice treated with dexamethasone developed significantly fewer dysplastic bony lesions compared to the age-matched, saline-treated controls. There was also a statistically significant difference in the quantity and cellularity of the middle ear effusions between the experimental and control animals.

Macrothrombocytopenia and progressive deafness: a new genetic syndrome.

We report a kindred with hereditary macrothrombocytopenia and progressive sensorineural hearing loss. Although the occurrence of hereditary sensorineural hearing loss associated with macrothrombocytopenia has been reported in a small number of families, varying degrees of renal pathology have always been present. In contrast to the previously reported syndromes involving a giant-platelet disorder and deafness, none of the family members in this report have had any evidence of renal dysfunction. The disorder was inherited in a linear pattern from great-grandmother to grandmother to mother to daughter. The clinical manifestations include hearing impairment that begins before the third decade and progresses to severe to profound bilateral hearing loss by the fourth decade. The platelet disorder manifests in early childhood and persists lifelong, although it tends to remain subclinical. Hematologic and ultrastructural findings will be contrasted to those found in Alport syndrome.