Diagnosis of histoplasmosis in urine cytology: reactive urothelial changes, a diagnostic pitfall. Case report and literature review of urinary tract infections

Histoplasmosis not uncommonly causes systemic infection, particularly in immunocompromised patients. In systemic infection, the urinary tract is often involved, although the diagnosis of histoplasmosis in urine cytologic specimens has never been reported. Urinary tract histoplasmosis may present with gross hematuria, raising clinical suspicion for malignancy. The index case presented with intermittent gross hematuria, suprapubic pain, significant weight loss, hoarse voice, and a painful tongue ulcer. Examination of the patient revealed an ulcerated tongue lesion, an anal ulcer, a polypoid lesion on the vocal cord, and cystoscopic examination of the urinary bladder revealed erythematous patchy areas. Surgical biopsy sections from the vocal cord and tongue lesion were diagnostic of histoplasma infection. Urine cytologic examination showed atypical urothelial cells suspicious for malignancy. However, fungal stains performed on the urine specimen showed histoplasma organisms. We conclude that with a high index of suspicion, and the use of special stains, histoplasma organisms can be identified in urine.     

The elastin gene is disrupted in a family with a balanced translocation t(7;16)(q11.23;q13) associated with a variable expression of the Williams-Beuren syndrome

The Williams-Beuren syndrome (WBS) is a complex developmental disorder with multisystemic manifestations including supravalvular aortic stenosis (SVAS), a so-called elfin face, a hoarse voice, and a specific cognitive phenotype. Most WBS patients have a >1 Mb deletion on one of their chromosomes 7 in q11 but except for elastin, whose haploinsufficiency causes the cardiovascular malformations, it is unknown which genes in the deletion area contribute to the phenotype. We have investigated a family with a cytogenetically balanced translocation t(7;16)(q11.23;q13) in which affected individuals manifested a broad spectrum of clinical phenotypes ranging from a hoarse voice as the only feature to the full WBS phenotype. Molecular cytogenetic and DNA sequence analyses of the translocation breakpoint showed that the cytogenetic rearrangement disrupts the elastin gene locus within intron 5 in the exact same manner in all translocation carriers. The recently described large inversion of the 7q11.23 region was not present in this family. Our data demonstrate that disruption of the elastin gene by a translocation breakpoint may cause classical WBS, atypical WBS, SVAS, or no recognisable phenotype, and provide a clear example for extensive phenotypic variability associated with a position effect in humans.     

Multidimensional voice program analysis (MDVP) and the diagnosis of pediatric vocal cord dysfunction.

BACKGROUND: Vocal cord dysfunction (VCD) can present with signs and symptoms that mimic asthma. This may lead to unnecessary pharmacologic treatment or more invasive measures including intubation. Presently, the diagnosis of VCD can only be confirmed when a patient is symptomatic, via pulmonary function testing (PFT) or visualization of adduction of the vocal cords during inspiration by direct laryngoscopy. OBJECTIVE: Multidimensional Voice Program (MDVP) analysis. a computer program which analyzes various aspects of voice, can detect abnormal voice patterns of patients with upper airway pathology. We determined whether MDVP analysis was useful in the diagnosis of VCD. METHODS: We conducted chart reviews of patients referred to our department from 1995 to 1998 with the presumed diagnosis of VCD who had undergone MDVP analysis. The diagnosis of VCD was based on the presenting history, PFT results, laryngoscopy results, as well as voice evaluation conducted by a speech-language pathologist. We analyzed six consecutive patients referred for this investigation. We delineated common trends in the variables measured on MDVP analysis in VCD patients. and compared these with controls and other vocal cord pathology. RESULTS: Five cases of possible VCD had abnormalities in the MDVP variable of soft phonation index (SPI). All five also had abnormalities in the variation in fundamental frequency (vFo). In one case, MDVP analysis was conducted pre- and posttreatment for VCD, and SPI and vFo both normalized. In a sixth case of possible VCD. the diagnosis was not confirmed as the patient had normal PFTs and laryngoscopy. MDVP analysis was normal in this individual. The pattern of abnormal SPI and vFo was not seen in a group of normal controls or in patients with vocal cord nodules. CONCLUSIONS: MDVP analysis may be a useful tool when diagnosingVCD, as well as in evaluating response to treatment.     

一种喉部疾病口语声诊断新方法

本文提出了声带的三质量块模型,并应用这种模型模拟病嗓产生的嘶哑语声。这些嘶声包括有声带闭合不全、声带小结、声带麻痹、喉炎、声带淀粉样变和声门癌等十六种典型情况。采用快速傅里叶变换、线性预测、倒谱技术和离散余弦变换等方法,分析各类喉病引起的嘶哑语声,实验结果表明声带模型分析法是喉病诊断的一种有效方法。     

一种用于喉部疾病语声诊断的新的声带模型

本文提出了一种新的声带模型－非对称四质量块声带模型，给出了它的数学表达式和等效电路，说明了在ＩＢＭ－ＰＣ微机上利用已知的语音信号拟合声带参数的方法，改进了语音嘶哑度的衡量方法，应用该模型对各种正常音和１６种典型喉部疾病患者手术前后的嘶哑语音进行分析比较，结果表明此模型的分析方法可作为喉部疾病诊断和嘶音分析的有效手段。     

喉部疾病的四质量块声带模型诊断方法研究

本文提出了一种新的声带模型－非对称四质量块声带模型，给出了它的数学表达式和等效电路，说明了在ＩＢＭ－ＰＣ微机上得已知的语音信号拟合声带参数的方法，改进了语音嘶哑度的衡量方法，最后应用这种模型对各种正常语音和喉疾患者术前术后的嘶哑语音进行了分析比较，实验结果表明此模型的分析方法可作为嘶音分析和喉疾诊断的一种手段。     

A gene-dosage PCR method for the detection of elastin gene deletions in patients with Williams syndrome

Williams syndrome (WS) is a multisystem developmental disorder associated with microdeletions at 7q11.23 that involve several genes, including the elastin gene. Using genomic DNA from a panel of normal individuals and WS patients with established hemizygosity of the elastin gene locus, we have developed a quantitative polymerase chain reaction (PCR)-based gene-dosage assay that rapidly detects the loss of one allele of the elastin gene. Using this procedure, we also studied a family in which the proband was previously diagnosed with WS and her mother with a balanced 7q translocation [t(7:11)(q34;q13)]. Using DNA isolated from buccal smears obtained from several individuals in this family we were able to establish normal disomy at 7q in all family members except for the proband, in which we established hemizygosity at the elastin gene locus. We were also able to successfully infer normal disomy in an unborn child in this family. The rapid diagnostic procedure described here may have a variety of applications, including fine mapping of deletion breakpoints at 7q11.23 associated with WS.     

Actinomycosis of the vocal cord: a case report

A 30-year-old Chinese lady was admitted for hoarseness of voice of one month's duration. Clinical examination revealed a granuloma of the left vocal cord while chest X-ray showed an opacity in the lower lobe of the right lung. The provisional clinical diagnosis was tuberculous laryngitis. A biopsy of the vocal cord lesion revealed inflamed tissue with actinomycotic colonies. Cultures and sputum smears did not reveal any tuberculous bacilli. The patient responded to a 6-week course of intravenous C-penicillin, regaining her voice on day 5 of commencement of antibiotics. A subsequent CT scan of the neck and thorax revealed multiple non-cavitating nodular lesions in both lung fields, felt to be indicative of resolving actinomycosis. She was discharged well after completion of treatment. It was felt that this is a case of primary actinomycosis of the vocal cord with probably secondary pulmonary actinomycosis.     

Nocturnal stridor in olivopontocerebellar atrophy

We describe a patient with olivopontocerebellar atrophy (OPCA) who was referred for alleged "snoring." Polysomnogram with video and audio monitoring revealed that the patient actually had nocturnal stridor causing repetitive oxygen desaturations. Direct laryngoscopy while awake showed a unilateral vocal cord paralysis. The nocturnal stridor persisted after unilateral vocal cord pinning, suggesting that the patient had probably been experiencing bilateral vocal cord paresis while asleep. We conclude that state-dependent vocal cord dysfunction may be severe in OPCA and related multiple system atrophy. Nocturnal stridor has many causes and may mimic snoring and obstructive sleep apnea syndrome. Polysomnography with audio and video recordings are necessary to make the diagnosis.     

Werner syndrome and mutations of the WRN and LMNA genes in France

Werner syndrome (WS) is a pleiotropic disease of premature aging involving short stature, tight, atrophied, and/or ulcerated skin; a characteristic 'birdlike' facies and high, squeaky or hoarse voice; premature greying and thinning of the hair; and early onset cataracts. Additional common symptoms include diabetes mellitus, hypogonadism, osteoporosis, osteosclerosis of the digits, soft tissue calcification, premature atherosclerosis, rare or multiple neoplasms, malformed teeth, and flat feet. Diagnosis can be difficult due to the variable presentation and rarity of the disorder. Transmission is usually autosomal recessive. The WS gene, WRN, is member of the RecQ DNA helicase family. Biallelic mutations of WRN are responsible for most patients. Although heterozygous missense mutations in the LMNA gene have been observed in severely affected WS patients, this only accounts for a small fraction of non-WRN patients. Eighteen WS cases were referred to us for molecular analysis. Eleven had definite and three had probable WS according to the University of Washington Registry clinical criteria. All exons of the WRN gene and their splice junctions were sequenced. Of the fourteen definite or probable cases, 11 had one or more WRN mutation. Thirteen different mutations were found, and ten of these were previously undescribed. There were few phenotypic differences between patients with WRN mutation(s) and those who met clinical criteria though lacking WRN mutations. However, patients with mutations tended to have more symptoms overall, and mutations were not observed in the two cases with cardiomyopathy.     

Delineation of the common critical region in Williams syndrome and clinical correlation of growth,heart defects,ethnicity, and parental origin

Williams syndrome (WS) is a neurodevelopmental disorder with a variable phenotype. Molecular genetic studies have indicated that hemizygosity at the elastin locus (ELN) may account for the cardiac abnormalities seen in WS, but that mental retardation and hypercalcemia are likely caused by other genes flanking ELN. In this study, we defined the minimal critical deletion region in 63 patients using 10 microsatellite markers and 5 fluorescence in situ hybridization (FISH) probes on chromosome 7q, flanking ELN. The haplotype analyses showed the deleted cases to have deletions of consistent size, as did the FISH analyses using genomic probes for the known ends of the commonly deleted region defined by the satellite markers. In all informative cases deleted at ELN, the deletion extends from D7S489U to D7S1870. The genetic distance between these two markers is about 2 cM. Of the 51 informative patients with deletions, 29 were maternal and 22 were paternal in origin. There was no evidence for effects on stature by examining gender, ethnicity, cardiac status, or parental origin of the deletion. Heteroduplex analysis for LIMK1, a candidate gene previously implicated in the WS phenotype, did not show any mutations in our WS patients not deleted for ELN. LIMK1 deletions were found in all elastin-deletion cases who had WS. One case, who has isolated, supravalvular aortic stenosis and an elastin deletion, was not deleted for LIMK1. It remains to be determined if haploinsufficiency of LIMK1 is responsible in part for the WS phenotype or is simply deleted due to its close proximity to the elastin locus. Am. J. Med. Genet. 78:82–89, 1998. © 1998 Wiley-Liss, Inc.     

Molecular cytogenetic diagnosis of Williams syndrome

Williams syndrome (WS) is characterized by distinct facial changes, growth deficiency, mental retardation, and congenital heart defect (particularly supravalvular aortic stenosis), associated at times with infantile hypercalcemia. Molecular genetic studies have indicated that hemizygosity at the elastin locus (7q11.23) causes WS. The purpose of this study was to confirm that this regional deletion, involving the elastin locus, is the cause of WS in Japan, and to clarify the correlation between the phenotype and the elastin locus. Thirty-two patients with WS and thirty of their relatives were examined by fluorescent in situ hybridization (FISH), using the WS chromosome region (WSCR) probe. All patients had cardiovascular disease (100%), 30 had typical WS facial changes (94%), 31 had mental retardation or developmental delay (97%), 16 were small-for-date at birth (50%), 14 had short stature (44%), and 13 had dental anomalies (41%). No relatives showed any manifestation of WS. Hemizygosity for a region of 7q11.23, involving the elastin locus, was found in all WS patients, but was not found in the 30 relatives. © 1996 Wiley-Liss, Inc.     

Morphometry of corpus callosum in Williams syndrome: shape as an index of neural development

Brain abnormalities in Williams syndrome (WS) have been consistently reported, despite few studies have devoted attention to connectivity between different brain regions in WS. In this study, we evaluated corpus callosum (CC) morphometry: bending angle, length, thickness and curvature of CC using a new shape analysis method in a group of 17 individuals with WS matched with a typically developing group. We used this multimethod approach because we hypothesized that neurodevelopmental abnormalities might result in both volume changes and structure deformation. Overall, we found reduced absolute CC cross-sectional area and volume in WS (mean CC and subsections). In parallel, we observed group differences regarding CC shape and thickness. Specifically, CC of WS is morphologically different, characterized by a larger bending angle and being more curved in the posterior part. Moreover, although CC in WS is shorter, a larger relative thickness of CC was found in all callosal sections. Finally, groups differed regarding the association between CC measures, age, white matter volume and cognitive performance. In conclusions, abnormal patterns of CC morphology and shape may be implicated in WS cognitive and behavioural phenotype.     

Detection of hemizygosity at the elastin locus by FISH analysis as a diagnostic test in both classical and atypical cases of Williams syndrome.

A small pilot study has been carried out in order to assess the reliability of the detection of hemizygosity at the elastin locus by fluorescence in situ hybridisation (FISH) analysis, as a diagnostic test in both classical and atypical cases of Williams syndrome (WS). Five subjects with WS and five others in whom a diagnosis could not be confirmed on clinical criteria alone were evaluated. Hemizygosity at the elastin locus by FISH analysis was detected in all classical Williams syndrome cases and in three of the five atypical subjects. Furthermore, a combination of a few specific facial features found to be present in all subjects with the elastin gene hemizygosity has been suggested to aid the index of clinical suspicion.     

Characterization of extracellular matrix proteins during wound healing in the lamina propria of vocal fold in a canine model: A long-term and consecutive study

The characterization of vocal fold wound healing can be reflected by the changes of extracellular matrix (ECM) proteins in the lamina propria. Although the expression of ECM proteins after vocal fold injury has been widely studied, such observations have lacked time continuity and integrity of marker proteins. In this study, we observed the morphology of injured vocal folds in a canine model. We used immunofluorescence staining to evaluate the expression and distribution of ECM proteins, such as collagen, elastin, hyaluronic acid, decorin and fibronectin, from 15 days to 6 months after injury. The results showed that large amounts of ECM proteins were secreted 15–40 days after injury. Collagen and fibronectin secretion increased significantly, and were disorderly deposited. The secretion of decorin and elastin increased slightly, while hyaluronic acid decreased. The 15–40 day post-injury period may be the critical intervention stage in wound healing of vocal folds. From 3 to 6 months after injury, the secretion of ECM proteins declined. However, collagen and fibronectin secretion were still significantly higher than normal with irregular arrangement, while the secretion of elastin, hyaluronic acid and decorin decreased significantly at 6 months. This led to vocal fold inelasticity and stiffness, which required effective long-term interventions to treat scar formation.     

Detection of an atypical 7q11.23 deletion in Williams syndrome patients which does not include the STX1A and FZD3 genes

We present two patients with the full Williams syndrome (WS) phenotype carrying a smaller deletion than typically observed. The deleted region spans from the elastin gene to marker D7S1870. This observation narrows the minimal region of deletion in WS and suggests that the syntaxin 1A and frizzled genes are not responsible for the major features of this developmental disorder and provides important insight into understanding the genotype-phenotype correlation in WS.     

Pleomorphic adenoma of the larynx

A 40-year-old woman was hoarse for five months due to a pleomorphic adenoma in the false vocal cord. The peripheral, ulcerated portion of the tumor had undergone squamous metaplasia, and this was initially misdiagnosed as squamous cell carcinoma. For that reason, the patient received radiation treatment, but the tumor remained unchanged. It was then locally excised, and the patient was still free of disease 14 years later. This case illustrates the hazard of misinterpreting squamous metaplasia in pleomorphic adenoma, the resistance of this tumor to irradiation, and the satisfactory long-range response to local excision.     

Chromosome 13q deletion with Waardenburg syndrome: further evidence for a gene involved in neural crest function on 13q.

Waardenburg syndrome (WS) is an autosomal dominant disorder characterised by pigmentary abnormalities and sensorineural deafness. It is subcategorised into type 1 (WS1) and type 2 (WS2) on the basis of the presence (WS1) or absence (WS2) of dystopia canthorum. WS1 is always caused by mutations in the PAX3 gene, whereas WS2 is caused by mutations in the microphthalmia (MITF) gene in some but not all families. An association of WS symptoms with Hirschsprung disease (HSCR) has been reported in many families. We report here a patient with characteristics of WS2 and a de novo interstitial deletion of chromosome 13q. We also describe a family with two sibs who have both WS2 and HSCR. In this family, all possible genes for WS and HSCR, but not chromosome 13q, could be excluded. As an association between chromosome 13q and HSCR/WS has been reported previously, these data suggest that there is a gene on chromosome 13q that is responsible for WS or HSCR or both.     

Sensorineural deafness, distinctive facial features, and abnormal cranial bones: a new variant of Waardenburg syndrome?

The Waardenburg syndromes (WS) account for approximately 2% of congenital sensorineural deafness. This heterogeneous group of diseases currently can be categorized into four major subtypes (WS types 1-4) on the basis of characteristic clinical features. Multiple genes have been implicated in WS, and mutations in some genes can cause more than one WS subtype. In addition to eye, hair, and skin pigmentary abnormalities, dystopia canthorum and broad nasal bridge are seen in WS type 1. Mutations in the PAX3 gene are responsible for the condition in the majority of these patients. In addition, mutations in PAX3 have been found in WS type 3 that is distinguished by musculoskeletal abnormalities, and in a family with a rare subtype of WS, craniofacial-deafness-hand syndrome (CDHS), characterized by dysmorphic facial features, hand abnormalities, and absent or hypoplastic nasal and wrist bones. Here we describe a woman who shares some, but not all features of WS type 3 and CDHS, and who also has abnormal cranial bones. All sinuses were hypoplastic, and the cochlea were small. No sequence alteration in PAX3 was found. These observations broaden the clinical range of WS and suggest there may be genetic heterogeneity even within the CDHS subtype.