Management of the fetus with a cystic adenomatoid malformation

Prenatal detection and serial sonographic study of fetuses with congenital cystic adenomatoid malformation (CCAM) now makes it possible to define the natural history of this lesion, determine the pathophysiologic features that affect clinical outcome, and formulate management based on prognosis. In a series of 22 prenatally diagnosed cases, the overall prognosis depended on the effects of the lung mass and the consequent physiologic derangement: A large mass may cause mediastinal shift, hypoplasia of normal lung tissue, polyhydramnios, and cardiovascular compromise leading to fetal hydrops. Two types of CCAM were distinguished by gross anatomy, ultrasonographic findings, and prognosis. Microcystic lesions (cysts < 5 mm; solid appearance) are often associated with fetal hydrops and have a poor prognosis. Macrocystic lesions (single or multiple cysts > 5 mm) are not usually associated with hydrops and have a more favorable prognosis. Four initially large lesions partially disappeared on serial prenatal sonography, suggesting that improvement can occasionally occur during fetal life. The finding that fetuses with hydrops are at high risk for fetal or neonatal demise led to fetal surgical resection of the massively enlarged pulmonary lobe (fetal lobectomy) in two cases. Fetuses with CCAM but without hydrops have a good chance for survival with maternal transport, planned delivery, and immediate neonatal resuscitation and surgery.

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Resumen La detección prenatal y el estudio sonográfico seriado de fetos con malformación adenomatosa quística congénita (MAQC) actualmente permite definir la historia natural de esta lesión, determinar las características patofisiológicas que afectan el resultado clínico y formular un manejo basado en pronóstico. En una serie de 22 casos diagnosticados en el período prenatal, el pronóstico global dependió de los efectos de las masas pulmonares y la consecuente alteración fisiológica: una gran masa puede producir desviación mediastinal, hipoplasia del tejido pulmonar normal, polihidramnios y compromiso cardiovascular resultante en hidrops fetal. Los dos tipos de MAQC pudieron ser distinguidos por la anatomía macroscópica, los hallazgos ultrasonográficos y el pronóstico. Las lesiones microquísticas (quiste <5 mm; apariencia sólida) generalmente están asociadas con hidrops fetal y tienen un pronóstico pobre. Las lesiones macroquísticas (quistes únicos/múltiples >5 mm) usualmente no están asociados con hidrops y exhibieron un pronóstico más favorable. Cuatro lesiones inicialmente de gran tamaño desaparecieron subsiguientemente bajo observación con sonografía seriada prenatal, lo cual sugiere que ocasionalmente se presenta mejoría en el curso del desarrollo fetal. El hallazgo de que los fetos con hidrops conllevan un alto riesgo de muerte fetal o neonatal ha llevado a la resección quirúrgica prenatal del lóbulo pulmonar de volumen masivo (lobectomía fetal) en dos casos. Los fetos con MAQC pero libres de hídrops tienen una buena probabilidad de sobrevivir mediante el transporte materno, un parto programado y resucitación y cirugía neonatales inmediatas.

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Résumé L'étude échographique répétée des foetus ayant la maladie kystique (adénomateuse) congénitale du poumon (MKACP) et la détection prénatale ont contribué à augmenter nos connaissances de l'histoire naturelle de la lésion, ont aidé à préciser les données physiopathologiques qui peuvent influencer l'évolution clinique et déterminer une démarche thérapeutique basée sur le pronostic. Dans cette série de 22 cas, diagnostiqués avant la naissance, le pronostic était basé sur l'effet de masse pulmonaire et les conséquences physiologiques: une masse importante peut en effet être responsable d'une déviation du médiastin, de l'hypoplasie des tissus pulmonaires normaux, d'une hydramnios, et d'une décompensation cardiovasculaire dont le résultat global est une anasarque foetale. Selon les données anatomiques macroscopiques, échographiques et pronostiques, on peut distinguer deux types de MKACP. Les kystes microscopiques (kystes < 5 mm, allure solide) sont souvent associés à une anarsaque foetale et un mauvais pronostic. Les lésions macroscopiques (kystes solitaires ou multiples > 5 cm) ne sont pas habituellement associés à une anasarque et le pronostic est généralement plus favorable. Dans cette série, quatre lésions larges initialement, ont diminué de taille au cours de la surveillance échographique, suggérant qu'une amélioration spontanée est toujours possible pendant la vie foetale. En raison du mauvais pronostic associé à une anasarque foetale avec mort foetale ou néonatale, on a été amené à pratiquer une résection chirurgicale élargie des lobes pulmonaires dans deux cas. Les foetus avec MKACP mais sans anasarque ont de bonnes chances de survie à condition d'entourer la maternité, la naissance et les premiers jours de l'enfant avec des soins chirurgicaux et de réanimation adaptés.

     

A comparison of oxymorphone and fentanyl as narcotic supplements in general anesthesia

The safety and efficacy of two potent opiate analgesics, fentanyl and oxymorphone, used as adjuncts in general anesthesia, were studied in 39 patients undergoing elective gynecologic surgery of at least 2 hours duration. Based on a potency ratio of 10:1, patients received either fentanyl 6.5 micrograms/kg or oxymorphone 65 micrograms/kg prior to a thiopental 2 to 3 mg/kg succinylcholine induction and endotracheal intubation. Additional maintenance narcotic and isoflurane were administered as required by the "blinded" anesthesiologist in response to hemodynamic alterations 15% above a presurgical baseline. Overall analysis included hemodynamic response at preset intraoperative intervals, total anesthetic requirements, and stability of vital signs in the recovery room. Blood pressure and heart rate were reliably controlled with either agent; however, less narcotic (ml) and recovery room analgesics were required in the oxymorphone-treated group (p less than 0.05). Decreased naloxone requirements (p less than 0.05) and a more rapid emergence suggested that fentanyl was a safer agent when administered in relatively unrestricted fashion.     

Visceral target organs in systemic St. Louis encephalitis virus infection of hamsters

Ultrastructural aspects of St. Louis encephalitis virus infection of the major extraneutral organs and tissues of suckling hamsters were examined. In the pancreas, both the exocrine and endocrine portions were equally affected by the virus. A feature apparently unique to flaviviruses was the accumulation of virus particles in all types of secretory granules in this organ. Virus particles were seen within myocardial fibers and within the smooth muscle cells and endothelial cells of small blood vessels of the heart. In the intestines, the lamina propria was the most severely infected, with virus particles accumulated in all cell types.     

An efficient method for cloning human autoantigen-specific T cells

T-cell clones are valuable tools for investigating T-cell specificity in infectious, autoimmune and malignant diseases. T cells specific for clinically-relevant autoantigens are difficult to clone using traditional methods. Here we describe an efficient method for cloning human autoantigen-specific CD4+ T cells pre-labelled with CFSE. Proliferating, antigen-responsive CD4+ cells were identified flow cytometrically by their reduction in CFSE staining and single cells were sorted into separate wells. The conditions (cytokines, mitogens and tissue culture plates) for raising T-cell clones were optimised. Media supplemented with IL-2+IL-4 supported growth of the largest number of antigen-specific clones. Three mitogens, PHA, anti-CD3 and anti-CD3+anti-CD28, each stimulated the growth of similar numbers of antigen-specific clones. Cloning efficiency was similar in flat- and round-bottom plates. Based on these findings, IL-2+IL-4, anti-CD3 and round-bottom plates were used to clone FACS-sorted autoantigen-specific CFSE-labelled CD4+ T cells. Sixty proinsulin- and 47 glutamic acid decarboxylase-specific clones were obtained from six and two donors, respectively. In conclusion, the CFSE-based method is ideal for cloning rare, autoantigen-specific, human CD4+ T cells.     

Structural change in dopamine D2 receptor gene in a patient with neuroleptic malignant syndrome

Dysfunction of the dopaminergic system has been suggested as a pathogenic mechanism in neuroleptic malignant syndrome. Therefore, we examined the complete coding sequences of the dopamine D₂ receptor (DRD₂) gene for structural abnormalities in 12 patients with a history of NMS, including two cases of familial NMS. Mutational analysis was performed by denaturing gradient gel electrophoresis (DGGE), a highly sensitive technique for detecting sequence differences. We found in one patient with a history of NMS a nucleotide substitution at codon 310 (CCG→TCG) of exon 7 of the DRD₂ gene which predicts the replacement of proline to serine in the third cytoplasmic loop of the receptor, a part of the receptor that interacts with G-proteins. A larger series of patients with NMS needs to be investigated to establish whether this allele is associated with an increased susceptibility to NMS. © 1995 Wiley-Liss, Inc.     

Simultaneous turnover of normal and dysfunctional C1 inhibitor as a probe of in vivo activation of C1 and contact activatable proteases.

Simultaneous turnover of normal and dysfunctional C1-inhibitor (C1-INH) was carried out in 10 normal subjects and 13 patients with rheumatoid arthritis as a measure of the in vivo activation of C1 and the contact activatable enzymes. In the first series of experiments, dysfunctional protein We was used in simultaneous turnover studies in five normal subjects and nine patients. The fractional catabolic rate of the dysfunctional C1-INH, We, (FCR(d)) was unchanged in both groups but the fractional catabolic rate of the normal C1-INH (FCR(n)) was faster in the patients compared to the controls, in particular patients with vasculitis. The enzyme-dependent catabolism defined as FCR(n-d) X concentration of C1-INH X plasma volume, was raised in the patient group, and correlated with disease activity score (r = 0.83, P less than 0.05). Neither FCR(n) nor FCR(d) was dependent on C1-INH concentration. The latter was higher in the patients (206 mg/l compared with 155 mg/l) indicating a very high synthetic rate in the patients (280.81 micrograms/kg/h compared with 179.77 micrograms/kg). In the second series of turnovers in six patients and five normal subjects, another dysfunctional C1-INH, at, was used. The FCR of C1-INH was slower than C1-INH (We) (1.88%/h compared with 2.7%/h). Enzyme-dependent catabolism of C1-INH in these patients were raised and also correlated with disease activity score (r = 0.82, P less than 0.05).