Isolated cardiac recurrence of acute lymphoblastic leukemia characterized by t(11;19) two years after unrelated allogeneic bone marrow transplantation

A 33-year-old male presented with acute lymphoblastic leukemia (ALL) characterized by translocation (11;19)(q23;p13.3). He received an allogeneic bone marrow transplant from a matched unrelated donor. Two years later his disease relapsed with an isolated intracardiac mass, presenting as right heart failure. He had no evidence of concomitant relapse in the bone marrow. Tumor cytogenetics revealed clonal evolution with the karyotype 46,XY,t(3;16)(q23;p13),t(11;19)(q23;p13.3), the chromosome 16 breakpoint involving the band where the genes for multidrug resistance-associated protein and CREB binding protein are known to reside. To our knowledge, this is the first report of an isolated extramedullary relapse of ALL in the heart.     

Pituitary pathology in erdheim-chester disease

Pituitary morphologic changes in patients with Erdheim-Chester disease have not been described in detail. We report here the histologic and immunohistochemical findings in the autopsy obtained pituitary of a 35-yr-old woman with extensively disseminated Erdheim-Chester disease. The posterior lobe was completely replaced by xanthogranulomatous infiltrates, providing an explanation for the patient’s diabetes insipidus. The anterior lobe was intact and immunohistochemistry demonstrated expression of GH, TSH, FSH, LH, and alpha subunit within the normal range. A clinically observed decrease of anterior pituitary function was interpreted as hypothalamic in origin due to massive destruction of the hypophysial stalk and compression of the hypothalamus. Prolactin immunoreactive cells were numerous, consistent with the view that prolactin cell hyperplasia resulted from the loss of hypothalamic dopaminergic inhibition. Massive Crooke’s hyalinization in the ACTH-producing cells was considered unrelated to Erdheim-Chester disease and was the consequence of treatment with pharmacologic doses of glucocorticoid hormones. It can be concluded that prolactin cell hyperplasia may be the only finding in the adenohypophysis of patients with disseminated Erdheim-Chester disease. It appears that in our patient the clinically apparent anterior hypopituitarism was not due to the lack of storage but rather to insufficient release of adenohypophysial hormones caused by the defect in hypothalamic regulation.     

Functional defects due to spacer-region mutations of human mitochondrial DNA polymerase in a family with an ataxia-myopathy syndrome

Defects of mitochondrial polymerase gamma (POLG) underlie neurological diseases ranging from myopathies to parkinsonism and infantile Alpers syndrome. The most severe manifestations have been associated with mutations of the 'spacer' region of POLG, the function of which has remained unstudied in humans. We identified a family, segregating three POLG amino acid variants, A467T, R627Q and Q1236H. The first two affect the spacer region and the third is a polymorphism, allelic with R627Q. Three grades of disease severity appeared to correlate with the genotypes. The patient with the most severe outcome, cerebellar ataxia syndrome, had all three variants, those with R627Q and Q1236H had juvenile-onset ptosis and gait disturbance and those with a single A467T allele had late-onset ptosis. To evaluate the molecular pathogenesis of these spacer defects, we expressed and purified the mutant proteins and studied their catalytic properties in vitro. The A467T substitution resulted in clearly decreased activity, DNA binding and processivity of the polymerase. Our biochemical data, the dominant manifestation of A467T and its previously reported high frequency in the Belgian population (0.6%), emphasize the role of this mutation as a common cause of neurological disease. Further, biochemical evidence that a polymorphic variant may modify the function of a mutant POLG, if occurring in the same polypeptide, is shown here. Finally, and surprisingly, other pathogenic spacer mutants showed DNA-binding affinities and processivities similar to or higher than the controls, suggesting that the disease-causing mechanisms of spacer mutations extend beyond the basic catalytic functions of POLG.     

Direct isolation of Candida spp. from blood cultures on the chromogenic medium CHROMagar Candida

CHROMagar Candida is a selective and differential chromogenic medium that has been shown to be useful for identification of Candida albicans, Candida krusei, Candida tropicalis, and perhaps Candida glabrata. Colony morphology and color have been well defined when CHROMagar Candida has been used to isolate yeast directly from clinical specimens, including stool, urine, respiratory, vaginal, oropharyngeal, and esophageal sources. Direct isolation of yeast on CHROMagar Candida from blood cultures has not been evaluated. We evaluated whether the color and colony characteristics produced by Candida spp. on CHROMagar Candida were altered when yeasts were isolated directly from blood cultures. Fifty clinical isolates of Candida were inoculated into aerobic and anaerobic blood culture bottles and incubated at 35 degrees C in an automated blood culture system. When growth was detected, an aliquot was removed and plated onto CHROMagar Candida. As a control, CHROMagar Candida plates were inoculated with the same isolate of yeast grown on Sabouraud dextrose agar simultaneously. No significant difference was detected in color or colony morphology between the blood and control isolates in any of the tested organisms. All C. albicans (n = 12), C. tropicalis (n = 12), C. glabrata (n = 9), and C. krusei (n = 5) isolates exhibited the expected species-specific colony characteristics and color, whether isolated directly from blood or from control cultures. CHROMagar Candida can be reliably used for direct isolation of yeast from blood cultures. Direct isolation could allow mycology laboratories to more rapidly identify Candida spp., enable clinicians to more quickly make antifungal agent selections, and potentially decrease patient morbidity and mortality.     

Human growth hormone and prolactin secreting pituitary adenomas analyzed by in situ hybridization

Acidophilic pituitary adenomas commonly produce growth hormone (GH) or prolactin (PRL), according to studies employing immunohistochemical and ultrastructural methods. To examine this question, in situ hybridization with oligonucleotide probes was done on routinely processed tissues received in the pathology laboratory to analyze for the presence of GH and PRL messenger RNA (mRNA) in 4 normal pituitaries, 10 prolactinomas, and 16 GH-secreting adenomas. Most acidophilic cells in normal pituitaries expressed either GH or PRL hormone and the respective mRNAs, but GH mRNA and PRL hormone were also detected in some of the same cells. Patients with a clinical diagnosis of prolactinoma had cells with only PRL mRNA in their tumors, while most (14 of 16) patients with a clinical diagnosis of acromegaly or gigantism had both GH and PRL mRNAs in their tumors. The GH adenomas varied in these studies. In situ hybridization was helpful in characterizing the adenoma from a patient with acromegaly who had immunoreactive PRL, but no immunoreactive GH in the resected tumor; in situ hybridization analysis revealed mRNAs for both GH and PRL in the same tumor cells. Our findings indicate that pituitary adenomas from patients with acromegaly commonly express PRL mRNA. It is concluded that in situ hybridization provides new information about the clinical biology and the histopathologic classification of pituitary adenomas.     

Association analysis between the human interleukin 1beta (-511) gene polymorphism and susceptibility to febrile convulsions

This study was designed to examine whether anxious personality, i.e. trait anxiety, influences the autonomic nervous functions in humans without manipulation of experimental stressors. The degrees of state and trait anxiety, blood pressure, heart rate, pupillary light reflex (PLR), and body temperature were measured at the same hour on four different days in 14 healthy college students. A multiple regression analysis showed that trait anxiety predominantly influenced state anxiety and the PLR parameters. A single regression analysis showed that trait anxiety positively correlated to the initial pupillary diameter and the constricted diameter of PLR and negatively to the amplitude of PLR. It was concluded that trait anxiety predicts state anxiety and a smaller amplitude of PLR in humans at rest.     

Characteristics of very poor outcome schizophrenia

The authors compared 21 "Kraepelinian" schizophrenic patients who had been ill and dependent on others for the past 5 years with 76 chronic schizophrenic patients in remission or with exacerbations requiring hospitalization. The Kraepelinian patients met the criteria for schizophrenia by more diagnostic systems than the exacerbated patients, were less responsive to haloperidol, had more severe negative symptoms, and had similarly severe positive symptoms. They had cerebral ventricles that were more asymmetrical and a greater family history of schizophrenia spectrum disorders than the other chronic patients. These data suggest that patients with 5 years of illness and complete dependency on others may represent a subgroup of schizophrenia.     

Overview and update on molecular testing in non-small cell lung carcinoma utilizing endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) samples

Lung carcinoma remains one of the most frequent and aggressive human neoplasms. Fortunately, in the last decades, the increasing knowledge of the molecular mechanisms leading to cancer development has allowed the use of targeted therapies with improvement of prognosis in many patients. Clinical management has also changed after the introduction of endobronchialultrasonographic bronchoscopy that allows a conservative staging of lung tumors, avoiding the need of mediastinoscopy for lymph node staging. Lung pathologists and cytopathologists are facing the challenge of giving the more comprehensive prognostic and predictive information with ever smaller tissue or cytological samples. The aim of this review is to summarize the molecular testing for non-small cell lung carcinoma and how pathologists can contribute to the patient's outcome with a conscious management of biological samples.     

Cerebral abscesses in children

Summary The authors analyze 81 cases of cerebral abscess in children admitted to the Clinic of Neurosurgery Bucharest, from 1936 to 1964; these cases represent 15 per cent of the total number of 542 cerebral abscesses treated in the clinic.A progressive increase was found in the incidence of cerebral abscesses during the last 10 years; an increase was also observed with the increase in age-group.Of the 81 cases 49 occurred in boys.In accordance with their origin there were: 56% contiguous cerebral abscesses (46% otogenic, 6% rhinogenic, 4% other causes); 17% were associated with the congenital cyanotic disease; 15% were post-traumatic abscesses and 12% of undetermined origin.The location was supratentorial in 56 cases, infratentorial in 23 cases and supra- and infratentorial in 2 cases. There were 17 frontal locations, 17 temporal locations, 4 parietal, 2 occipital; in 10 cases two lobes were involved, in 4 cases three lobes and in 1 case one of the cerebral hemispheres. There were 23 cerebellar abscesses and in 2 cases the abscess was supra- and infratentorial.The clinical picture was dominated by the syndrome of raised intracranial pressure (80 per cent of the cases); the evolution of almost half of the cases was afebrile.Among the clinical features of cerebral abscesses in children particular stress is laid on cerebral abscess in infants and on abscesses accompanying a congenital cyanotic cardiopathy.The difficulties of differential diagnosis with focal encephalities, cortical thrombophlebitis, otogenic hydrocephalus, cerebral tumour, etc. are discussed.The treatment of cerebral abscesses in children is considered by the authors as a neurosurgical emergency. They recommend total ablation of the abscess as the best method of treatment, because of the favourable, immediate and late results (the formation of a supple cicatrix) it offers. The surgical treatment was associated with antibiotics, antioedematous medication, corticotherapy and anticonvulsants.Of the 75 children operated on 42 recovered and 12 showed improvement. There was no lethal case in the 25 cerebral abscesses operated on during the last 5 years.

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Zusammenfassung Die Autoren geben eine Analyse von 81 Fällen kindlicher Hirnabszesse, die zwischen 1936 und 1964 in der Neurochirurgischen Klinik Bukarest beobachtet wurden. In dieser Zeit wurden insgesamt 542 Hirnabszesse behandelt. Die kindlichen machen davon 15% aus. Die Häufigkeit hat in den letzten Jahren zugenommen. Die Hirnabszesse sind bei älteren Kindern häufiger. Sie kommen bei Knaben häufiger vor als bei Mädchen.56% waren fortgeleitet entstanden (46% otogen, 6% rhinogen, 4% andere Ursachen). 17% traten im Verlauf angeborener Herzmißbildungen mit Zyanose auf. 15% entstanden posttraumatisch. Bei 12% war die Ursache nicht zu klären.56 Fälle lagen supratentoriell, 24% infratentoriell und 2 sowohl supra- als auch infratentoriell. 17 waren frontal, 17 temporal, 4 parietal und 2 okzipital lokalisiert. Bei 10 Fällen waren zwei Hirnlappen, bei 4 Fällen drei und bei 2 Fällen eine ganze Hirnhemisphäre befallen. Bei 23 Fällen fand sich der Abszeß im Kleinhirn.Das klinische Bild wurde von den Zeichen intrakranieller Drucksteigerung (80%) beherrscht. Beinahe 50% der Fälle verliefen afebril.Auf die Besonderheiten des Hirnabszesses bei Säuglingen und bei angeborenen Herzmißbildungen im Rahmen des Morbus Coerulius wurde eingegangen. Die Schwierigkeiten der Diagnose und der differentialdiagnostischen Abgrenzung von Herdenzephalitiden, kortikaler Thrombophlebitis, otogenem Hydrozephalus, Hirntumoren usw. wurden besprochen. Der diagnostische Wert von EEG, Angiographie und Kontrastdarstellung des Abszesses wurde betont.Als Behandlung der Wahl gilt die Totalexstirpation, weil sie die besten Früh- und Spätergebnisse gewährleistet und die resultierende Hirnnarbe weniger derb ist. Zusätzlich wurden Antibiotika, Osmotherapeutika, Kortikoide und Antiepileptika gegeben.Von 75 operierten Kindern genasen 42. Bei 12 weiteren wurde eine Besserung erzielt. In den letzten 5 Jahren wurde bei 25 operierten Kindern kein Todesfall mehr verzeichnet.

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Resumen Los autores presentan el análisis de 81 casos de absceso cerebral en niños, casos que se investigaron en la Clínica de Neurocirurgía de Bucarest entre los años 1936 y 1964 y que representan un 15% del total de los 542 abscesos cerebrales registrados en la clínica.Se comprueba un crecimiento progresivo de la frecuencia de los abscesos cerebrales en los últimos 10 años; se observa tambien que la frecuencia crece paralelamente al aumento de la edad de los niños.Predominan los abscesos cerebrales entre los varones (49 casos).Según su origen se encontraron: 56% abscesos cerebrales subyacentes (46% otógenos, 6% rinógenos, 4% debidos a otras causas); 17% abscesos asociados a la enfermedad cianógena congénita; 15% abscesos post-traumáticos y 12% abscesos de origen indeterminado.Desde el punto de vista de su localización, hubo 56 casos supratentoriales, 23 casos infratentoriales y 2 casos supra e infratentoriales. Con localización frontal hubo 17 casos, temporal 17 casos, parietal 4 casos y occipital 2 casos; en 10 casos, el absceso afectó 2 lóbulos, en 4 casos 3 lóbulos y en 2 casos un hemisferio cerebral. 23 abscesos fueron cerebelosos y 2 situados encima y debajo del tentorio.El síndrome de hipertensión intracraneana predominó en el cuadro clínico (80% de los casos); y casi la mitad de los casos evolucionaron sin fiebre.Entre las peculiaridades clínicas del absceso cerebral infantil se ponen de relieve los abscesos cerebrales entre los niños de pecho y los que se asocian a una cardiopatia cianógena congénita.Se discuten las dificultades que encuentra el diagnóstico del absceso infantil en comparación con la encefalitis en el foco, la tromboflebitis cortical, la hidrocefalia otógena, el tumor cerebral, etcétera.Los exámenes paraclínicos subrayan el valor de la electroencefalografia, de la arteriografia cerebral y de la abscesografia.El tratamiento de los abscesos infantiles impone, según los autores, la urgencia neuroquirúrgica; basados en su experiencia, ellos recomiendan como método exclusivo de tratamiento la ablación total del absceso, por dar este método los resultados más favorables tanto inmediatos como ulteriores (permitiendo la formación de una cicatriz cerebral más blanda. El tratamiento quirúrgico se asoció a una medicación antibiótica, antiedematosa, a la corticoterapia y al empleo de anticonvulsivos.De los 74 niños operados sanaron 42 y mejoraron 12. En los últimos 5 años, entre los 25 abscesos cerebrales infantiles operados, no se registró ningún caso de fallecimiento.

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Résumé Les auteurs présentent l'analyse clinique de 81 cas d'abcès cérébraux chez l'enfant, opérés dans la Clinique Neurochirurgicale de Bucarest (Roumanie), depuis 1936 jusqu'à 1964. Ces cas représentent 15% du nombre total de 542 abcès cérébraux hospitalisés dans cette période.On a pu constater, surtout dans les deux dernières années, une fréquence plus grande aussi bien qu'un accroissement du nombre des cas par rapport aux groupes d'âge des enfants.Le nombre de cas chez les garçons (49) l'a emporté sur ceux de l'autre sexe. La répartition des cas d'après leur origine fut la suivante: abcès de voisinage: 56% (dont 46% otogènes, 6% rhinogènes et 4% d'origine différente); abcès associes à une maladie cyanogène congénitale: 17%; abcès posttraumatiques: 15%; abcès d'origine indéterminée: 12%.La répartition des cas d'après la localisation: 56 cas furent des abcès supratentoriels, 23 cas soustentoriels et 2 cas mixtes. Parmi les 56 cas à localisation supratentorielle 17 étaient dans le lobe frontal; 17 dans le lobe temporal, 4 dans le lobe pariétal et 2 dans le lobe occipital; dans 10 cas l'abcès s'étendait à deux lobes, dans 4 cas à trois lobes et dans 2 cas l'abcès envahissait tout un hemisphère cérébral.Un syndrome d'hypertension intracranienne dominait l'aspect clinique dans 80% des cas et environ la moitié des cas eurent une évolution afébrile.Les auteurs insistent sur les particularités cliniques des abcès cérébraux chez le nourrisson et sur ceux accompagnant une cardiopathie cyanogène congénitale.On discute les difficultés diagnostiques de l'abcès cérébral chez les enfants surtout avec l'encéphalite en foyer, avec la trombophlébite corticale, l'hydrocéphalie otogène et les tumeurs cérébrales.Parmi les investigations paracliniques, on souligne la valeur de l'electroencéphalogramme, de l'angiographie cérébrale et de l'abcessographie.Les auteurs insistent sur le caractère d'urgence neurochirurgicale et, de par leur expérience, sont d'avis que le seul traitement qui puisse assurer les meilleurs résultats aussi bien immédiats que tardifs (cicatrice cérébrale plus souple) est l'ablation totale de l'abcès.Une médication antibiotique et antioedémateuse aussi bien qu'une corticotherapie et, des anticonvulsivants ont été constamment associées au traitement chirurgical.Du nombre de 75 enfants opérés, 42 ont été complètement guéris et 12 ameliorés. Dans les derniers 5 ans, il n'y eut aucun decès parmi les 25 enfants opérés pour abcès cérébral.

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Riassunto Gli AA. fanno l'analisi clinica di 81 casi di ascessi cerebrali nei bambini, osservati nella Clinica Neurochirurgica di Bucarest, dal 1936 al 1964, e scelti tra 542 casi di ascessi osservati nello stesso periodo.Si nota un accrescimento notevole della casistica negli ultimi 10 anni e con l'età del malato; il sesso maschile è stato molto più frequentemente colpito (49 casi).Dal punto di vista dell'eziologia sono stati riscontrati: 56% di ascessi per contiguità, tra cui: 46% ascessi otitici, 6% ascessi rinogeni e 4% da altre cause; 17% associati a cardiopatie cianogene congenite, 15% ascessi post-traumatici e 12% ascessi d'origine sconosciuta.La sede degli ascessi è stata molto variabile: 56 ascessi erano sopratentoriali, 23 ascessi sottotentoriali e 2 sopra- e sottotentoriali insieme. Tra gli ascessi sopratentoriali sono stati osservati: 17 casi in sede frontale, 17 in sede temporale, 4 in sede parietale e 2 in sede occipitale. In 20 altri casi risultavano lesi 2 lobi cerebrali, in quattro 3 lobi ed in un caso un emisfero intero.In quadro clinico era dominato dclla sindrome di ipertensione endocranica (80% dei casi); il 50% dei malati era apirettico.Tra le forme cliniche dell'ascesso cerebrale nei bambini, si mettono in rilievo quello del neonato e quello associato alla cardiopatia cianogena congenita.Vengono indicate inoltre brevemente le difficoltà di una diagnosi differenziale tra encefalite a focolaio, tromboflebite corticale, l'idrocefalia otitica ed i tumori cerebrali. Tra le indagini paracliniche si sottolinea l'importanza dell'elettroencefalografia, dell'angiografia cerebrale e dell'ascessografia con aria.La terapia degli ascessi cerebrali nei bambini costituiscono, secondo gli AA., una necessità neurochirurgica urgente e, come tale, il metodo chirurgico di elezione è l'asportazione totale dell'ascesso, visto che i risultati, tanto immediati quanto a distanza, sono migliori dopo l'operazione: per es. si ha una gliosi cerebrale meno retrattile e quindi una minore frequenza dell'epilessia.Alla cura chirurgica si è associato la terapia antibiotica, la medicazione dell'edema cerebrale, i cortisonici ed i farmaci anticonvulsivi.Tra i 75 casi operati si notano: 42 guarigioni e 12 miglioramenti clinici. Negli ultimi 5 anni non si deplora nessun caso mortale nei 25 ascessi cerebrali operati.

     

Predicting esthetics of laminate veneers without tooth preparation

High expectations may contribute to stress in the patient and dentist during dental treatment. Esthetic and restorative results can be predicted for laminate veneers by using a powder blower and a liquid dispenser preoperatively to form self-cured resin veneers. Trial veneers are formed in a precision "salt and pepper" technique that conserves materials and time. The trial veneers are placed, without tooth preparation, on the treatment site so that the patient can preview the planned treatment and so that the dentist can explain proposed treatment in a reversible procedure. This may circumvent misunderstandings between dentist and patient and allow the consideration of alternate treatment plans.