A patient- and observer-rated analysis of the impact of lateral rhinotomy on facial aesthetics.

OBJECTIVE: To determine, using patient- and observer-rated facial disfigurement measures, whether a lateral rhinotomy imparts significant aesthetic morbidity. DESIGN: Retrospective and subject-controlled study in a large, tertiary-referral, academic otolaryngology department. Twenty-one consecutive patients who had undergone lateral rhinotomy for the treatment of inverted papilloma were studied in the long-term. MAIN OUTCOME MEASURES: Scores on the following: (1) the novel Patient-Rated Facial Disfigurement Analogue Scale questionnaire and (2) the reliable and validated Observer-Rated Facial Disfigurement 9-Point Likert Scale. RESULTS: Patients rated their facial appearance as minimally altered and significantly less apparent to others. The observers in this study, a surgeon (J.C.I.) and a psychiatrist (M.R.K.), rated the patients' facial disfigurement as minimally visible. Patients seem to rate how apparent their appearance is to others in a similar fashion to observers. The observer-rated facial disfigurement scale used is valid and reliable. CONCLUSION: Patient- and observer-rated facial disfigurement measures suggest that a lateral rhinotomy does not impart significant aesthetic morbidity.

Reliability and validity of an observer-rated disfigurement scale for head and neck cancer patients.

BACKGROUND: Facial disfigurement is considered to be one of the most distressing aspects of head and neck cancer and its treatment, but it has been the focus of little systematic study. Existing studies have yielded conflicting results about the psychosocial impact of disfigurement. No studies to date have examined disfigurement using a valid and reliable observer-rated measure. The purpose of the current study was to examine the validity (convergent and discriminant) and the inter-rater reliability of a novel nine-point observer-rated disfigurement scale. METHODS: The sample consisted of 74 ambulatory head and neck cancer patients more than 6 months post treatment. Ratings of disfigurement were assigned independently by surgical and nonsurgical raters. Validity was assessed by comparing the association between disfigurement ratings and sociodemographic and illness treatment variables. Reliability was assessed by examining the concordance between the surgical and nonsurgical ratings. RESULTS: Disfigurement ratings were not associated with several sociodemographic variables, supporting the discriminant validity of the scale. Disfigurement was significantly related to a diagnosis of oral cancer, a history of adjunctive radiation, the type of surgical procedure performed, the degree of physical dysfunction, and the presence of postoperative complications. Observer ratings of disfigurement were significantly related to patient ratings of disfigurement. These findings support the convergent validity of the disfigurement scale. Inter-rater reliability of the scale was high (intraclass correlation coefficient =.91). CONCLUSION: The study provides preliminary evidence for the validity and inter-rater reliability of a novel nine point observer-rated disfigurement scale that may be useful in evaluating the impact of disfigurement on quality of life in head and neck cancer.

Accuracy of clinical impressions and Mini-Mental State Exam scores for assessing capacity to consent to major medical treatment. Comparison with criterion-standard psychiatric assessments.

The authors evaluated the accuracy of clinical impressions and Mini-Mental State Exam scores for assessing patient capacity to consent to major medical treatment, relative to expert psychiatric assessment. Consecutive medical inpatients (N = 63) facing a decision about major medical treatment received a clinical impression of capacity from their treating physician and the Standardized Mini-Mental State Exam (SMMSE); 48 received independent psychiatric assessment of capacity. Analyses revealed that both clinical impressions and SMMSE scores were generally inaccurate in determining capacity, although all 23 participants with a clinical impression of "definitely capable" were found capable by the psychiatrist. Given the importance of assessing capacity to consent to major medical treatment, better approaches to the clinical assessment of capacity are required. Several strategies are discussed.

Self-esteem and cancer: theory and research.

OBJECTIVE: To examine the relationship between self-esteem and the psychosocial response to cancer. METHODS: The authors review methodological issues associated with measuring self-esteem in patients with cancer and examine existing empirical studies in light of these issues. RESULTS: Self-esteem in cancer has been variously viewed as an outcome variable, a mediator of other psychosocial outcomes, and as a personal resource that facilitates coping. Unidimensional measures of global self-esteem have been most often employed in research studies, despite increasing recognition that self-esteem is multidimensional. Evaluation of global self-esteem has generally revealed no differences between cancer patients and controls. Aspects of multidimensional self-esteem, particularly body self-esteem, appears to be disturbed in many patients with cancer. CONCLUSIONS: The clinical and theoretical literature have emphasized the importance of self-esteem to the psychosocial response to cancer. Empirical study of self-esteem in cancer has been limited by conceptual and methodological issues. Strategies for future research are discussed.

Spontaneous migration of an intracranial bullet into the cervical canal.

We have reported a case of intracranial to intraspinal migration of a retained bullet fragment over a course of approximately 4 years. The patient remained asymptomatic. The bullet was removed via a posterior cervical laminectomy. Migration of bullet fragments, though rare, should be included as one of the delayed complications of gunshot wound to the head.

Clinical, pathologic, and biochemical features of a cholesterol lipidosis accompanied by hyperlipidemia and xanthomas.

We describe the unique clinical and histopathologic features of a child with biochemical and immunocytochemical features of Niemann-Pick disease type C (NPC). Clinically, she was found to have multiple xanthomas of the upper aerodigestive tract with dysphagia and expressive language delay, splenomegaly, bony infarcts, and type IIb hyperlipidemia. Neurologic examination was otherwise normal. Microscopy revealed foam cells in her bone marrow, liver, tongue, tonsils, glottis, and in normal-appearing peritonsillar mucosa. Lipid analysis of a liver biopsy specimen showed a small increase in phospholipids, a twofold increase in sphingomyelin, a fivefold increase in cholesterol, and a marked (25-fold) increase in bis(monoacylglycerol) phosphate. Lysosomal acid hydrolase activities in cultured skin fibroblasts were nondiagnostic. Biochemical and immunocytochemical studies of cultured fibroblasts demonstrated lysosomal accumulation of unesterified LDL-derived cholesterol as well as delayed induction of homeostatic responses to endogenous cholesterol consistent with a diagnosis of NPC. Based upon these observations, we speculate that this patient could have a new phenotypic expression of NPC or represents a new cholesterol lipidosis biochemically resembling NPC. The chance occurrence of two separate lipid disorders seems less likely.

Terminal transverse limb defects associated with familial cavernous angiomatosis.

Terminal transverse limb defects rarely are reported as familial. Multiple pathogenetic mechanisms, including vascular disruption, have been proposed to account for these defects. We report on a family followed over the past 6 years known to have familial cavernous angiomatosis in which 2 relatives have similar terminal transverse defects at the mid-forearm. Multiple relatives have had episodic bleeding from intracranial cavernous angiomas, a distinct finding in this disorder. Other findings in this family include retinal cavernous angiomas (2 patients), a high incidence of skin angiomas (12 patients), cavernous angiomas of the soft tissue (2 patients), and a hepatic angioma (one patient). One of the 2 individuals with the limb defect was evaluated extensively. Magnetic resonance imaging of the forearm with the terminal transverse defect using gadolinium-DTPA enhancement showed abrupt termination of all structures distal to the normal radial and ulnar heads. We propose that familial cavernous angiomatosis may be a new cause of vascular disruption resulting in terminal transverse limb defects.

Ophthalmologic manifestations of type B Niemann-Pick diseases.

Type B Niemann-Pick Disease (NPB) is a rare lysosomal storage disease resulting from diminished activity or deficiency of sphingomyelinase and is characterized by multi-system involvement with visceromegaly. Rare ocular involvement (the Macula Halo Syndrome) has been reported. Eight patients (ages 4-36) with NPB underwent complete ophthalmologic evaluations. All patients had periorbital fullness, a hitherto unreported clinical feature. Two patients had a classic Macula Halo Syndrome. One patient developed peri-macular granular deposits forming an incomplete Macula Halo over 5 years. Another patient had macular granular deposits and developed deterioration of central vision and abnormal visual evoked potentials. Ophthalmologic involvement in NPB is more common than previously described. Complete ophthalmologic evaluation is recommended in all patients suspected to have NPB.

Pseudocyesis in organic mood disorders. Six cases.

Pseudocyesis, the delusion of pregnancy, has had an uncertain nosology, primarily because of the concentration on the content of the beliefs and lack of interest in the underlying phenomenology. Six patients with a major mood disorder caused by cerebral dysfunction are presented in this article. The delusion is reviewed with respect to the entities it overlaps, and the clinical manifestations are related to the mood disorders. Although no clear neuroanatomic localization was possible with this group of patients, there may be some association with desomatization caused by parietal lobe dysfunction.

Genetic flanking markers refine diagnostic criteria and provide insights into the genetics of Von Hippel Lindau disease.

Von Hippel Lindau disease (VHL) is a hereditary syndrome, associated with tumors and cysts in multiple organ systems, whose expression and age of onset are highly variable. The availability of a genetic test for the early and reliable detection of individuals carrying the defective gene would be beneficial for VHL patients and their relatives, since many of the manifestations of VHL can be successfully treated if detected in their early stages, while the complications of undetected disease can be devastating. We have previously shown that the VHL gene maps to chromosome 3p. To provide genetic markers for the development of a reliable diagnostic test, and to further narrow and eventually clone the VHL defect, we have generated DNA markers for chromosome 3p. With these markers, we have performed a multipoint genetic linkage analysis in 28 VHL pedigrees, comprising 470 individuals, 164 of whom were affected with VHL. Here we report the identification of tightly linked markers, including flanking markers that bracket the VHL gene to a small region on chromosome 3p25-p26. This finding has several major implications. While visceral cysts of the kidney, pancreas, and epididymis are commonly found in VHL and are considered diagnostic criteria for this disorder, they also occur in the general population. The presence of cysts, unaccompanied by other more typical lesions such as retinal and cerebellar hemangioblastoma, may therefore represent a major diagnostic problem, leading to errors in the assessment of disease status. The application of flanking markers for the VHL gene for presymptomatic diagnostic testing confirms that epididymal cysts are indeed not suitable as a diagnostic criterion in this disorder. Pheochromocytomas occur nonuniformly in VHL families and may also be associated with other hereditary tumor syndromes; our genetic studies imply that the phenotype in VHL families with and without pheochromocytomas is caused by defects within the same gene. The absence or presence of this tumor type is therefore due to the pleiotropic expression of a single gene rather than to the existence of several different genes for VHL. The region on chromosome 3p13-p14 known to contain several chromosomal translocation breakpoints in families with "pure familial renal cell carcinoma" is quite proximal to the VHL locus in 3p25-p26 we have identified. Chromosome 3p may therefore contain two loci for renal cell carcinoma: one gene (or genes) in 3p13-p14 and the VHL gene in 3p25-p26, whose aberration is also associated with other typical manifestations of VHL. Since renal cell carcinoma, pheochromocytoma, and visceral cysts can occur sporadically even in young people and may also be associated with other tumor syndromes, the availability of flanking markers for the VHL gene will be useful in identifying VHL gene carriers, particularly among those individuals at risk in whom these are the only manifestations of disease. The isolation and characterization of the VHL gene, based on the identification of flanking markers, will have important implications for diagnosis and treatment of patients with VHL, as well as for a much larger number of individuals having the sporadic counterparts of VHL-associated tumor types.

Simple renal cysts, atypical renal cysts, and renal cell carcinoma in von Hippel-Lindau disease: a lectin and immunohistochemical study in six patients.

We compare the expression of four markers of renal tubular differentiation in six renal cell carcinomas, five atypical renal cysts, and five simple renal cysts from six patients with von Hippel-Lindau disease. Proximal tubular markers were expressed by five of six renal cell carcinomas, three of five atypical renal cysts, and zero of five simple renal cysts. Distal tubular markers were expressed by one of six renal cell carcinomas, five of five atypical renal cysts, and four of five simple renal cysts. One of the three atypical cysts which expressed distal tubular markers was associated with a renal cell carcinoma which also expressed distal tubular markers. Our findings suggest that simple renal cysts in von Hippel-Lindau disease arise more commonly from distal rather than proximal tubules, while atypical renal cysts show tubular origin similar to renal cell carcinomas.

Central nervous system involvement in Von Hippel-Lindau disease.

Fifty individuals with Von Hippel-Lindau disease (VHL) were studied with gadolinium-enhanced magnetic resonance imaging (MRI) to determine the frequency and distribution of CNS lesions. The associated clinical features were also reviewed. Thirty-six (72%) of the 50 had 1 or more CNS tumors. The most frequently affected sites in the CNS excluding the retina were the cerebellum (52%), spinal cord (44%), and brainstem (18%). New regional predilections for the craniocervical junction and conus medullaris were demonstrated by this study. Forty-one percent of all VHL patients with CNS tumors were neurologically asymptomatic: cerebellar tumors (50%), spinal cord tumors (50%), and brainstem tumors (44%) were often without clinical signs or symptoms. Multiple lesions were common. The mean age of all VHL patients (34.5 years) was similar to the mean age of all CNS VHL patients (34.4 years), suggesting a lack of age association. CNS lesions commonly occurred in the 2nd decade of life. All patients at risk for VHL should be evaluated using gadolinium-enhanced MRI after 10 years of age, although ophthalmic examination should be initiated within the 1st 2 years of life. Enhanced MRI is particularly useful in the detection of CNS tumors in patients with the VHL gene.

Identifying genes determining trait differences in behavior and drug response: a comment on 'Quantitative trait loci and psychopharmacology'.

In Plomin, McClearn and Gora-Maslak's target article (see also Science 248: 183-188, 1990), reverse genetic approaches are emphasized for locating genes determining behavioral and pharmacogenetic traits. Furthermore, prospects for such an undertaking are presented pessimistically in that behavioral traits are asserted to be polygenic (due to the simultaneous action of variant alleles at multiple loci) and are conceptualized as being determined in large part by unshared environmental factors. We disagree with Plomin et al. in three major areas and argue the following:(1) Forward genetic approaches involving candidate locus analysis and detailed analysis of the phenotype are of primary importance for isolating genes for behavioral traits, as for other genetic traits.(2) Virtually all physiologic processes and metabolic pathways involve sets of genes, resulting in genetic heterogeneity (multiple genetic origins for a trait). However, polygenicity is approximately as unusual for behavioral traits as for other traits.(3) Heritability analyses underestimate the extent to which behavioral traits are amenable to genetic analysis and have been misinterpreted to overestimate the importance of environmental factors.

Papillary cystadenoma of the epididymis. A report of three cases with lectin histochemistry.

Papillary cystadenoma of the epididymis is an uncommon benign tumor associated with von Hippel-Lindau disease. Since metastatic renal cell carcinoma may be histologically similar to papillary cystadenoma, and both are associated with von Hippel-Lindau disease, differentiation between these two entities may be difficult. We performed lectin histochemistry studies on three papillary cystadenomas and compared the results with the staining observed in epididymal ducts, epididymal efferent ductules, and three renal cell carcinomas. Common positive staining was observed following incubation with soybean agglutinin in epididymal ducts and two of the three papillary cystadenomas, while the three renal cell carcinomas did not stain. When epididymal tumors histologically consistent with papillary cystadenoma fail to react with soybean agglutinin, thorough clinical evaluation for an occult renal cell carcinoma should be performed.

Gadopentetate dimeglumine enhanced MRI in an anephric patient on dialysis.

Gadopentetate dimeglumine (Gd-DTPA) was injected into an anephric patient on maintenance haemodialysis. Sequential serum Gd levels before and after dialysis demonstrated incomplete removal of the administered dose. No clinical sequelae were observed. Gd-DTPA can be given to patients on dialysis, but like iodinated contrast media, may require more than one session for complete removal.

von Hippel-Lindau disease: radiologic screening for visceral manifestations.

The visceral manifestations of von Hippel-Lindau (VHL) disease can cause significant morbidity and mortality. The authors prospectively screened 37 persons from a single kindred. Twenty-five subjects underwent abdominal ultrasound (US), contrast material-enhanced abdominal computed tomography (CT), and nonenhanced abdominal magnetic resonance (MR) imaging. Eight subjects younger than 16 years of age underwent abdominal US and MR imaging only. Scrotal US was employed in 25 male patients. Eleven subjects had renal cysts or tumors. Contrast-enhanced CT depicted renal abnormalities in 10 of these subjects, US in seven, and MR imaging in nine. Among 12 subjects with pancreatic cysts or tumors, CT showed pancreatic abnormalities in all 12, US in nine, and MR imaging in nine. Three subjects (mean age, 34.5 years) had renal tumors, and three had pancreatic masses. Scrotal US revealed epididymal cystadenomas in seven subjects; two of these tumors were surgically verified. A combination of contrast-enhanced CT and scrotal US in male patients appears to be the best way to screen for visceral manifestations of VHL disease.

Radiologic screening for von Hippel-Lindau disease: the role of Gd-DTPA enhanced MR imaging of the CNS.

Thirty-seven members of a family with von Hippel-Lindau disease (VHL) were prospectively screen for CNS hemangioblastomas; 10 family members were previously known to have VHL. Radiographic studies included noncontrast magnetic resonance (MR) imaging of the head (all patients) and spine (34 patients) and contrast-enhanced CT (CCT) of the head (all adult patients). Eleven patients had Gd-DTPA enhanced MR (CMR) of the head and 10 patients had CMR of the spine. Sixteen patients had radiographic evidence of CNS hemangioblastomas and all but six patients were symptomatic. Using comparable studies, CMR of the head demonstrated more lesions than the other modalities (31, 22, and 19 for CMR, MR, and CCT, respectively). Furthermore, CMR better separated tumor from edema, as well as cystic from solid components. Contrast enhanced MR was superior to noncontrast MR of the spine in lesion detection (31 vs. 4; p less than 0.001). Noncontrast MR was particularly limited in four patients with syringomyelia. We conclude that postcontrast MR of the head and spine is the best currently available means of detecting hemangioblastomas associated with VHL.

Clinical spectrum of Niemann-Pick disease type C.

Analysis of the neurologic symptomatology in 22 patients with Niemann-Pick disease type C revealed 3 phenotypes: (1) an early-onset, rapidly progressive form associated with severe hepatic dysfunction and psychomotor delay during infancy and later with supranuclear vertical gaze paresis, ataxia, marked spasticity, and dementia; (2) a delayed-onset, slowly progressive form heralded by the appearance, usually in early childhood, of mild intellectual impairment, supranuclear vertical gaze paresis, and ataxia, and later associated with dementia and, variably, seizures and extrapyramidal deficits; (3) a late-onset slowly progressive form distinguished from the 2nd pattern by later age of onset (adolescence or adulthood) and a much slower rate of progression. The existence of the 1st and 2nd phenotypes within the same sibship suggests that they are variant expressions of the same clinicopathologic disorder. Niemann-Pick disease type C should be considered not only in infants and children who present with organomegaly and a progressive neurodegenerative course, but also in adolescents and adults who have insidiously progressive neurologic dysfunction and only slight organomegaly. Associated with the disease is a marked deficiency in the ability of cultured fibroblasts to esterify exogenously supplied cholesterol. Assay of this deficiency is particularly useful for confirming the diagnosis in patients with atypical presentation.