Lethal neonatal Menkes' disease with severe vasculopathy and fractures

A male neonate presented with an acute onset of severe intra-abdominal bleeding, haemorrhagic shock and multiple fractures leading to death on d 27. Menkes' disease was diagnosed at autopsy and confirmed by copper accumulation studies on cultured fibroblasts. Such an early onset of fatal complications in this condition has not been previously reported. New insights into the pathogenesis of Menkes' disease provided by DNA mutation analysis and difficulties in neonatal diagnosis are discussed. Menkes' disease should be considered in male infants with pathological fractures and other signs of connective tissue disease, even in the neonatal period.     

Dummies and the sudden infant death syndrome

The association between dummy use and sudden infant death syndrome (SIDS) was investigated in 485 deaths due to SIDS in the postneonatal age group and compared with 1800 control infants. Parental interviews were completed in 87% of subjects. The prevalence of dummy use in New Zealand is low and varies within New Zealand. Dummy use in the two week period before death was less in cases of SIDS than in the last two weeks for controls (odds ratio (OR) 0.76, 95% confidence interval (CI) 0.57 to 1.02). Use of a dummy in the last sleep for cases of SIDS or in the nominated sleep for controls was significantly less in cases than controls (OR 0.44, 95% CI 0.26 to 0.73). The OR changed very little after controlling for a wide range of potential confounders. It is concluded that dummy use may protect against SIDS, but this observation needs to be repeated before dummies can be recommended for this purpose. If dummy sucking is protective then it is one of several factors that may explain the higher mortality from SIDS in New Zealand than in other countries, and may also explain in part the regional variation within New Zealand.     

CAESAREAN SECTION — CHANGING TRENDS DURING LAST TWO DECADES

Changing trends of caesarean section during last twenty years have been studied. There seems to be a gradual increase in the incidence of caesarean section over the years with a simultaneous decline in the perinatal mortality rate. The incidence of caesarean section has slowly been increasing for post-caesarean pregnancy, breech presentation and foetal distress. This opens up a debate as to what extent this increase is justifiable. The trend needs a close observation.KEY WORDS: Cesarean section, Trends     

The effect of rhGH in vitro on donor-specific hyporesponsiveness in pediatric transplantation

Recombinant human growth hormone (rhGH) improves growth in children after renal transplantation, but may be associated with augmented immune responses. To understand the effect of rhGH in transplantation, we evaluated the role of rhGH in a mixed leukocyte culture (MLC) in vitro. We demonstrated that PBMC isolated from normal adult volunteers cultured in an MLC in the presence of rhGH develop an augmented proliferative (25-400%) and cytotoxic (50-600%) response. Using in situ hybridization (ISH), we demonstrated that the frequency of cells expressing mRNA for IFNgamma increased in the presence of rhGH (100-800%). In vitro responses of PBMC from adults in an MLC may only loosely reflect responses in vivo during pediatric transplantation. After transplantation, adults develop decreased responses to donor-specific antigens in an MLC (donor-specific hyporesponsiveness - DSH). We evaluated the donor-specific responses of 20 pediatric patients who had each received a renal allograft from one parent. Pediatric patients developed DSH similarly to adults; however, no correlation was seen between the amount of DSH and graft function. We also evaluated the expression/production of IFNgamma and IL4 in response to donor-specific alloantigens. Patients exhibit marked DSH of IFNgamma expression and production. However, IL4 production was seen in 8 out of 10 patients with normal renal function, but only 1 out of 7 patients with biopsy proven chronic rejection. Finally, we evaluated the effect of rhGH in vitro on DSH. Only 3 out of 20 patients developed augmented donor-specific responses in the presence of rhGH in vitro. rhGH augments proliferation, cytotoxicity and IFNgamma expression during an MLC. After renal transplantation, rhGH augments donor-specific responses during an MLC in some pediatric patients.     

The Potency of Allospecific Tregs Cells Appears to Correlate With T Cell Receptor Functional Avidity

CD4⁺CD25⁺ regulatory T cells (T_reg cells) are an attractive adoptive cell therapy in mediating transplantation tolerance. T‐cell receptor (TcR) activation is critical for T_reg function, suggesting that the TcR avidity of T_reg cells used in therapy may affect the therapeutic outcome. To address this, we compared the regulatory capacity of T_reg lines expressing TcRs derived from two TcR transgenic mice shown to have the same specificity but different functional avidities. T_reg lines generated from CD4⁺CD25⁺ T cells from C57BL/6 mice were transduced with one of either of these TcRs. The antigen specificity of the transduced T_reg lines was confirmed in vitro. T_reg lines expressing the TcR with higher functional avidity showed stronger suppressive capacity in a linked suppression model in vitro. Furthermore, the same T_reg lines demonstrated a stronger proliferation in vivo following antigen exposure. Pretreatment of recipient BL/6 mice with these T_reg cells, together with anti‐CD8 antibody and Rapamycin therapies, prolonged survival of BALB/c skins, as compared with mice that received T_reg lines with lower TcR avidity. Taken together, these data suggest that the TcR functional avidity may be important for T_reg function. It highlights the fact that strategies to select T_reg with higher functional avidity might be beneficial for immunotherapy in transplantation.     

Cutaneous T-cell lymphoma treated with electron beam irradiation in Indian patients

BACKGROUND: Cutaneous T-cell lymphoma (CTCL) is a rare occurrence in India. Total skin electron irradiation (TSEI) is a well-accepted therapeutic modality for the treatment of CTCL throughout the world. The aim of this study was to retrospectively analyze the treatment outcome of TSEI in Indian patients with CTCL and to determine the different parameters affecting the disease-free survival in these patients. METHODS: Fourteen male patients between 27 and 82 years of age with CTCL (duration of disease, 4 months to 2 years) were treated with TSEI between 1985 and 1998. Seven patients had early stage disease, while the other seven had advanced disease. Two patients had lymph node involvement at the time of presentation. The TSEI was performed according to the Stanford technique delivering a total dose in the range 8-36 Gy. RESULTS: Of the 14 patients, 10 showed complete remission following TSEI. The total follow-up period was 4-110 months (median, 52 months). Five patients were disease free at the end of 5 years. Two patients died due to rapid progression of the disease, while the cutaneous lesions relapsed in three patients after 2-27 months and one patient developed visceral metastasis. CONCLUSIONS: TSEI was an effective therapeutic modality for the treatment of CTCL in this group of patients, both as a curative and palliative measure, although the long-term prognosis is poor.     

Value of radio-active brain scans in the diagnosis of brain tumors as compared with other methods

Summary The physical and clinical properties of two recently introduced radioactive tracers, the mercury²⁰³ and mercury¹⁹⁷ labeled Neohydrin were discussed. Both gave scans of adequate quality. The advantage of Hg¹⁹⁷ is the considerably lesser kidney radiation as compared with Hg²⁰³. The value of the photoscan was stressed as compared to the dot scan. The simplicity, safety and lack of discomfort of the radioactive brain scan was emphasized. The difficulties in the detection of brain tumors at the base of the skull and in the posterior fossa were pointed out. In our series of 90 consecutive intracranial tumors the overall evidence of positive and localizing scans was 75.6%. The supratentorial tumors were more readily detected (83%) as compared with the infratentorial ones (47.3%).Of a total of 80 angiographic studies performed on the same group of tumors 71.2% were positive, localizing the lesion accurately in 55% of cases.Pneumoencephalography and ventriculography were less frequently employed in brain tumor diagnosis. The results were satisfactory. The electroencephalograms were of little localizing value in the diagnosis of our series of brain tumors (12 out of 30).The glioblastomas (92%) and meningiomas (94.1%) have most consistently given accurately localizing findings with this technique. High incidence of positive and localizing scans was also obtained with intracranial sarcomas and metastatic tumors. The more benign and less vascular tumors such as astrocytomas and acoustic neurinomas have shown a lesser tendency to pick up the radioactive material. Completely benign and avascular tumors such as the epidermoids did not display increased pick up of the radioactive substance. No differential diagnosis as to the tumor type is possible on the basis of the scan alone. Since other lesions than brain tumors have shown up in the radioactive brain scan, the differential diagnosis as to the type of the lesion can not be made safely with this technique. The unquestioned value of a good history, thorough neurological examination and classical contrast studies in the diagnosis of brain tumors was emphasized. Although the brain scan is the best single localizing procedure in brain tumor diagnosis it should not be used as a screening test for presence or absence of brain tumors, since a positive scan, generally speaking, means only a lesion (neoplastic or non-neoplastic) with a certain localization and a negative scan has no diagnostic value whatsoever.

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Zusammenfassung Die physikalischen und klinischen Eigenschaften zweier kürzlich eingeführter radioaktiver Substanzen, das Quecksilber 203 und Quecksilber 197 markierte Neohydrin, wurden diskutiert. Beide ergeben Scannings gleicher Qualität. Der Vorteil von Quecksilber 197 liegt in der bedeutend geringeren Strahlenbelastung der Nieren im Vergleich zum Quecksilber 203. Der Wert des Photoscannings im Vergleich zum Punktscanning wurde herausgestellt. Die Einfachheit, Sicherheit und das Fehlen von Beschwerden beim radioaktiven Hirnscanning wurde betont. Die Schwierigkeiten des Nachweisens von Hirntumoren an der Scl ädelbasis, der hinteren Schädelgrube und parasagittaler Lokalisation wurden beschrieben.In unserer Serie von 90 intrakraniellen Tumoren war der Gesamtnachweis durch positive und lokalisierende Scannings 75,6%. Die supratentoriellen Tumoren konnten leichter nachgewiesen werden (83%), wenn man sie mit den infratentoriellen vergleicht (47,3%).Von insgesamt 80 angiographischen Untersuchungen, die an der gleichen Tumorgruppe vorgenommen wurden, waren 71,2% positiv, der Tumor wurde in 55% der Fälle richtig lokalisiert. Pneumenzephalographien und Ventrikulographien wurden weniger häufig zur Hirntumordiagnostik durchgeführt. Die Ergebnisse waren befriedigend. Elektroenzephalogramme hatten einen geringen lokalisatorischen Wert in der Diagnostik unserer Serie von Hirntumoren (12 von 30).Glioblastome (92%) und Meningeome (94,1%) ließen sich am häufigsten mit dieser Technik lokalisieren. Intrakranielle Sarkome und metastatische Tumoren konnten ebenfalls mit einer großen Wahrscheinlichkeit durch positive und lokalisatorische Scannings nachgewiesen werden. Gutartigere und wenig vaskularisierte Tumoren, wie Astrocytome und Akustikusneurinome, zeigten eine geringere Tendenz, das radioaktive Material aufzunehmen. Völlig gutartige und avaskuläre Tumoren, wie Epidermoide, ergaben keine erhöhte Aufnahme der radioaktiven Substanz. Durch das Scanning allein konnte keine Differentialdiagnose des Tumortyps erzielt werden. Da andere Läsionen als Hirntumoren sich in dem radioaktiven Hirnscan dargestellt haben, kann die Differentialdiagnose in bezug auf die Art der Läsion mit dieser Technik nicht sicher gestellt werden. Der unbestrittene Wert einer guten Anamnese, gründlichen neurologischen Untersuchung und der klassischen Kontrastmitteluntersuchung in der Diagnostik der Hirntumoren wurde betont. Obwohl das Hirnscanning als solches die beste lokalisierende Untersuchung in der Hirntumordiagnostik ist, sollte es doch nicht als genereller Test für das Vorhandensein oder Fehlen eines Hirntumors benutzt werden, da ein positiver Scan — um es allgemein auszudrücken — nur eine Läsion (neoplastisch oder nicht neoplastisch) in einer bestimmten Lokalisation darstellt und ein negativer Scan absolut keinen diagnostischen Wert hat.

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Resumen Se discuten las propiedades físicas y biológicas de dos indicadores radioactivos recientemente presentados, el mercurio²⁰³ y el mercurio⁹⁷, llamado Neohydrine. Ambos proporcionan examenes de igual calidad. La ventaja del Hg¹⁹⁷ es su considerable menor radiación en comparación con la del Hg²⁰³. El valor del examen fotográfico quedó reforzado en relación con el examen local. La simplicidad, seguridad y facilidad del examen radio-activo del cerebro son subrayadas. También se destacan las dificultades de detección de los tumores de la base del craneo y de la fosa posterior así como aquellos de las localizaciones parasagitales.En nuestra serie de 90 tumores cerebrales consecutivos los diagnósticos evidentes, positivos y topográficos, fueron del 75,6%. Los tumores supratentoriales fueron detectados con más seguridad (83%) que los infratentoriales (47%).En un total de 80 estudios angiográficos practicado en el mismo grupo de tumores un 71,2% fueron positivos localizando la lesión con precisión en un 55% de los casos.La encefalografia gaseosa y la ventriculografía se emplearon menos frecuentemente para el diagnóstico de los tumores cerebrales. Los resultados fueron satisfactorios. El electroencefalograma fué de escaso valor localizador en el diagnóstico de nuestra serie de tumores cerebrales (12 en 30).Los glioblastomas (92%) y los meningiomas (94,1%) han proporcionado de un modo más consecuente localizaciones precisas con esta técnica. Un gran número de examenes positivos y localizadores pudo obtenerse también en los casos de sarcomas intracraneales y de metástasis.Los tumores más pequeños y menos vascularizados, como los astrocitomas y los neurinomas del acústico demostraron una menor tendencia para fijar los cuerpos radio-activos. Los tumores pequeños y avasculares, como los epidermoides, no aparecìan aumentados y llenos de substancia radio-activa. No pudo hacerse ningún diagnóstico diferencial por lo que se refiere al tipo de tumor con este registro. El valor indiscutable de un buen interrogatorio, lo mismo que el examen neurológico y los estudios clásicos de contraste se ponen de manifiesto. Aunque la gammaencefalografía cerebral sea el procedimiento de localización más sencillo para el diagnóstico de los tumores del cerebro no puede emplearse como un test eliminatorio para la presencia ó ausencia de tumores cerebrales, ya que un examen positivo, hablando en términos generales, demuestra solamente una lesión (neoplásica ó no neoplásica) con una localización segura pero un examen negativo no tiene ningún valor diagnóstico.

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Résumé Les propriétés physiques et biologiques de deux traceurs radio-actifs récemment présentés, le mercure²⁰³ et le mercure¹⁹⁷ nommé Neohydrine furent discutés. Tous les deux donnent des examens d'une qualité égale. L'avantage du Hg¹⁹⁷ est sa considérablement moindre radiation par rapport à celle du Hg²⁰³. La valeur de l'examen photographique fut renforcée par rapport à l'examen local. La simplicité, la sûreté, la facilité de l'examen radio-actif du cerveau sont soulignées. Les difficultés de détection des tumeurs de la base du cerveau et dans la fosse postérieure sont signalées.Dans notre série de 90 tumeurs cérébrales consécutives, les diagnostics positifs et topographiques évidents furent de 75,6%. Les tumeurs supratentorielles furent plus surement détectées (83%) que les tumeurs infratentorielles (47,3%).Sur un total de 80 études angiographiques pratiquées dans le même groupe de tumeurs, 71,2% furent positives, localisant les lésions avec précision dans 55% des cas.L'encéphalographie gazeuse et la ventriculographie furent moins souvent employées dans le diagnostic des tumeurs cérébrales. Les résultats furent satisfaisants. Les electroencéphalogrammes furent de peu de valeur localisatrice dans le diagnostic de notre série de tumeurs cérébrales (12 sur 30).Les glioblastomes (92%) et les méningiomes (94,1%) ont donné de façon plus conséquente des localisations précises avec cette technique. Un grand nombre d'examens positifs et localisateurs furent aussi obtenus dans les cas de sarcomes intracrâniens et de metastases. Les tumeurs plus petites et moins vasculaires telles que les astrocytomes et les neurinomes de l'acoustique ont montré une tendance moindre à fixer les corps radio-actifs. Les tumeurs tout à fait minimes et avasculaires telles que les tumeurs epidermoïdes n'apparaissent pas grossies et pleines de substance radio-active. Aucun diagnostic différentiel pour ce qui est du type de la tumeur n'est possible sur la seule base de l'enregistrement. Depuis que d'autres lésions que les tumeurs du cerveau ont été mises en évidence lors d'examens radio-actifs du cerveau, le diagnostic différentiel sur le type de la tumeur ne peut être fait sûrement avec cette technique. La valeur incontestée d'un bon interrogatoire de même que l'examen neurologique et des examens de contraste classiques est soulignée. Quoique la gammaencéphalographie cérébrale soit le procédé de localisation le plus simple dans le diagnostic des tumeurs du cerveau, elle ne peut pas être employée comme un test éliminatoire pour la présence ou l'absence de tumeurs cérébrales, puisque un examen positif, généralement parlant, désigne seulement une lésion (néoplastique ou non néoplastique) avec une localisation certaine et qu'un examen négatif n'avait aucune valeur diagnostique quoi qu'il en soit.

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Riassunto Vengono discusse le proprietà fisiche e cliniche di due traccianti radio-attivi recentemente introdotti in clinica, la neoidrina marcata con il mercurio 203 e con il mercurio 197. Ambedue i traccianti danno delle scansioni di ottima qualità. Il vantaggio del Hg 197 è rappresentanto dalla minor irradiazione renale rispetto al Hg 203. Il valore della scansione fotografica è confrontato con quello della scansione a punti. Viene anche sottolineata la semplicità, la sicurezza e la mancanza di danni per il paziente rappresentati da questa tecnica. Vengono poi discusse le difficoltà di diagnosi dei tumori della base cranica e della fossa posteriore e di quelli a localizzazione parasagittale.Nella serie presentata di 90 scansioni consecutive per tumori endocranici la diagnosi è stata possibile nel 75,6% dei casi. Questa percentuale è stata più alta per i tumori sopratentoriali (83%) dei casi, rispetto a quelli sottotentoriali (47,3%).Su di un totale di 80 angiografie praticate sugli stessi pazienti il 71,2% è risultato positivo, mentre la lesione è stata localizzata accuratamente solo nel 55% dei casi.La pneumoencefalografia e la ventricolografia sono state usate meno frequentemente nella diagnosi dei tumori cerebrali. I risultati sono soddisfacenti. L'EEG è stato di scarso valore localizzatorio per la diagnosi dei tumori cerebrali (12 su 30).I glioblastomi (92% dei casi) ed i meningiomi (94,1%) sono stati localizzati molto accuratamente. Un'alta incidenza di localizzazioni è stata ottenuta in casi di sarcomi intracranici e di tumori metastatici. I tumori più benigni e meno vascolarizzati come gli astrocitomi ed i neurinomi dell'acustico hanno una minor tendenza a concentrare del materiale radioattivo,Dei tumori completamente benigni ed avascolari come gli epidermoidi non manifestano alcuna concentrazione elettiva del materiale radioattivo. Nessuna diagnosi differenziale del tipo di tumore è possibile mediante la scansione. Anche lesioni diverse da quelle tumorali possono essere localizzate mediante questa tecnica. Il valore di una buona storia clinica accompagnato da evidenze neurologiche e dai classici studi con mezzi di contrasto è sottolineato. Malgrado che la scansione con isotopi radioattivi sia la miglior tecnica singolarmente intesa, per la diagnosi dei tumori cerebrali, essa non deve essere presa in considerazione con test di screening per la presenza o l'assenza di tumori cerebrali, in quanto una scansione positiva, in senso generico, significa solamente la presenza di una lesione (neoplastica o non-neoplastica), con una certa localizzazione ed una scansione negativa non ha comunque valore diagnostico.

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Presented at the Congress of Neurological Surgeons, Miami, Florida on November 19, 1964.

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Aided in part by Training Grant No. NB-5408 from the National Institute of Neurological Diseases and Blindness of the U. S. Public Health Service.