Abnormalities of the neonatal brain: MR imaging. Part I. Intracranial hemorrhage

The authors prospectively evaluated 82 neonates, ranging in gestational age from 29 to 44 weeks postconception, with magnetic resonance (MR) imaging at 0.6 T. Twenty-two cases of hemorrhage in 15 infants were identified. Ultrasound (US) and computed tomography (CT) were superior to MR in the first few days after parenchymal hemorrhage, since at this time lesions were apparent on only T2-weighted images. After the first 3 days, MR was the single best modality because (a) hemorrhage on CT became imperceptible in the 2d week, whereas the high signal of hemorrhage on MR persisted for 2-11 weeks; (b) MR permitted rough dating of hemorrhage according to changes in signal intensity; and (c) MR was superior in identifying subdural or epidural hemorrhage. Because of the nonspecificity and restricted field of view of US and the inability of CT to depict hemorrhage after 7-10 days, the authors conclude that MR significantly improves the detection of intracranial hemorrhage in neonates.     

Botulinum toxin A in the hemiplegia upper limb: a double-blind trial

In a randomised, double-blind study, the effects of intramuscular injection of botulinum toxin type A (BtA) into the upper limb were compared with those of normal saline solution in 14 patients with cerebral palsy; their mean age was 9 years. Range of movement and function were assessed before injection and at 2 and 12 weeks after injection. BtA injection significantly increased maximum active elbow and thumb extension and significantly reduced tone at wrist and elbow. The hand grasp-and-release score improved, representing a modest functional change, but fine motor function, assessed by the ability to pick up coins, did not improve and in some cases deteriorated temporarily. The most notable subjective change was the cosmetic benefit of reduced involuntary elbow flexion. The tone-reducing effect of BtA was clinically detectable in comparison with the placebo and patients and parents perceived the change as beneficial. The median of changes in the treatment group was small but the range Was large, suggesting that BtA can be useful in selected patients.     

Gene transfer in vivo with DNA-liposome complexes: safety and acute toxicity in mice.

DNA can be introduced into a variety of cell types after formation of liposomal complexes with cationic lipids. In this report, conditions have been established to optimize the production of DNA-liposome complexes that efficiently transfect cells. The safety and toxicity of this method of gene delivery have been assessed after in vivo administration, either by intravenous or direct intratumor injection. Nine to eleven days after intravenous injection, DNA was found primarily in heart and lung tissue by PCR analysis. No abnormalities were evident from histologic examination of tissue, examination of tissue-specific serum enzymes, routine biochemical parameters, or electrocardiographic monitoring. DNA-liposome complexes can therefore be used for the delivery of recombinant genes in vivo with minimal toxicity.     

Mathematical modeling of platelet survival with implications for optimal transfusion practice in the chronically platelet transfusion- dependent patient

BACKGROUND: It is known that in vivo platelet survival varies as the platelet count changes. Previous attempts at curve fitting fail to predict the decreased platelet survival in thrombocythemia. Therefore, mathematical relations that more closely approximate platelet survival were derived and used in models of platelet transfusion practice. STUDY DESIGN AND METHODS: A differential equation for platelet loss was derived that included a constant (constant homeostatic loss), a first- order term (senescent loss), and a second-order term (one proportional to the square of the platelet concentration and whose contribution is expected to be significant only at higher platelet concentrations). Data derived from this model was compared to platelet survival data in normal, thrombocytopenic, and thrombocythemic patients and to the platelet decay after high-dose chemotherapy. To provide further validation of this model, predicted and actual platelet requirements were calculated or obtained (chart review) in bone marrow patients with uncomplicated thrombocytopenia after ablation and at two platelet- transfusion thresholds (20 and 10 × 10(9)/L). RESULTS: The equations accurately modeled normal, thrombocytopenic, and thrombocythemic platelet survival. Chart review demonstrated a 12.5 percent reduction in platelet transfusion requirements when the transfusion threshold was reduced from 20 to 10 × 10(9) per L. The model predicted a reduction of 14.0 percent. For 100 days of uncomplicated thrombocytopenia and a transfusion threshold of 10 × 10(9) per L, transfusion of 3 units of platelet concentrates compared to a 6-unit pool of platelet concentrates, resulted in a 22-percent savings of platelet units. CONCLUSION: Platelet survival as a function of platelet concentration can be modeled by use of a differential equation. This model challenges current dogma regarding platelet destruction and predicts decreased platelet survival in thrombocythemic patients. The model illustrates that large doses of platelets would result in greater time between transfusions, however, more units of platelets are used. Consideration should be given to the more frequent use of smaller doses of platelets in patients who chronically require platelet transfusion support.     

Antigen-specific T lymphocyte clones. I. Characterization of a T lymphocyte clone expressing antigen-specific suppressive activity

We have generated continuously propagatable T lymphocyte clones to study antigen-specific T cell functions. All Ly-2+ clones mediate suppressive activity and secrete a characteristic pattern of polypeptides that differs from Ly-2- T cell clones. Cells of one clone, Cl.Ly23/4, specifically bind glycophorin from sheep erythrocytes (SRBC). After incubation with [35S]methionine, supernate material from this clone also contains biosynthetically labeled 70,000-mol wt proteins that specifically bind to SRBC and this binding is inhibited by glycophorin from sheep but not other erythrocytes. These antigen-binding 70,000-mol wt peptides specifically and completely suppress primary anti-SRBC responses generated by mixtures of primed Ly-1+2- cells and B cells. Suppression by these antigen-binding peptides reflects direct inhibition of T-helper activity.     

Tailored hormonal therapy in secretory adrenocortical cancer

Mitotane is often considered the front-line hormonal therapyof adrenocortical carcinoma (ACC). An illustrative case concerningthis issue and the rationale to ponder other alternatives isreported. A 69 year-old woman, diagnosed with ACC was admittedwith hypertensive crisis, supraventricular tachycardia, congestiveheart-failure, diarrhoea and rabdomyolisis. Two years earlier,she had undergone     

Pregnancy following intracytoplasmic sperm injection treatment with dead husband's spermatozoa: ethical and policy considerations

This paper describes the first pregnancy in a childless widow after intracytoplasmic sperm injection (ICSI) treatment with her deceased husband's spermatozoa which had been stored for nearly 3 years before use. Before his death the husband had received treatment for testicular cancer and he had given the appropriate written consent for the future use of his spermatozoa. Of the 10 eggs injected, six resulted in normal embryos. Three embryos were transferred and the remaining three embryos are currently stored for possible future use. The treatment resulted in a continuing singleton pregnancy. The case demonstrated the suitability of ICSI in those difficult cases where the sperm quality is extremely poor. This success is also compared with a widely debated case of another widow who was refused permission to use her deceased husband's spermatozoa. It is concluded that in the case of posthumous use of frozen spermatozoa, the current laws are conveniently applicable in a chronic illness but not so in an acute illness leading to death. In the light of the wide public debate on the issues raised by this legal case, the UK Government has also decided to conduct a review of consent procedures involving the storage and use of genetic material.