Artificial blood: current status of hemoglobin solutions.

Attempts to develop a hemoglobin-based red cell substitute have spanned many decades, but no clinically useful product has been produced to date. The issues preventing clinical application primarily are ones of safety--not efficacy. Numerous animal studies have documented the efficacy of SFH. Although effective, the solution has limitations that have caused concern. Oncotic considerations limit the concentration of the infusate SFH to 6 to 8 g/dL, or half-normal. Owing to the loss of organic phosphate modulators of P50, such as 2,3-DPG, the P50 of SFH is typically between 12 and 14 mm Hg, which is also half the normal value. And finally, the intravascular half-life of SFH is too short, ranging only from 2 to 6 hr. Polymerization provides a means of correcting these limitations. The high oxygen affinity can be greatly diminished by covalent binding of pyridoxal-5'-phosphate to the N-terminal of the chains. Colloid osmotic pressure exerted by a protein solution is proportional to the number of discrete colloid particles. Through polymerization, the number of colloid particles is reduced, leading to a decrease in COP. Data show that this can be achieved in a reproducible fashion. The rate at which COP diminishes determines the yield of polymeric species, as well as their molecular weight distribution. Polymerization can be controlled to result in a yield of 75% to 85% polymers with a molecular weight distribution of 128 to 400 kd. The number average and the weight average molecular weights indicate that the large proportion of polymers represent the cross linking of two tetramers. The data that reflect the interaction of oxygen with poly-SFH-P indicate that the oxygen carrying function of hemoglobin has not been significantly altered by the chemical modifications. The binding coefficient of oxygen is unchanged. As anticipated, there is a loss of cooperativity (diminished Hill coefficient) between the hemoglobin chains, suggesting structural restrictions in the polymeric species because of cross linking. A reduced alkaline Bohr effect is the expected result, and data confirm this. Finally, some increase in oxygen affinity is to be expected with polymerization. This is indeed the case, although the P50 of poly-SFH-P is comparable to banked blood (18 to 22 mm Hg). To be clinically useful, a modified hemoglobin solution requires a reasonable shelf-life.(ABSTRACT TRUNCATED AT 400 WORDS)     

Inhibition of HLA B8-restricted recognition by unrelated peptides: evidence for allosteric inhibition

A panel of synthetic peptides representing human lymphocyte antigen (HLA) B8, other class I and class II restricted T cell epitopes and two B cell epitopes, were all able to compete with recognition of a HLA B8 restricted epitope by a cytotoxic T cell clone. Competition was obtained when the competitor peptides were added either before or after the target epitope. The target epitope also had a slow off rate, implicating allosteric inhibition. The presence of non-specific, allosteric binding sites may interfere with experiments attempting to define immunologically relevant MHC binding specificities.     

High-dose VP-16 with intermediate-dose cytosine arabinoside in the treatment of relapsed acute nonlymphocytic leukemia

Summary In a study of 11 adult patients with acute nonlymphocytic leukemia (ANLL), infusion therapy with high-dose VP-16 and intermediate-dose cytosine arabinoside was administered. Response was assessed with reference to bone marrow aspirations performed on days 1; 12, 13, or 14; and 21 of treatment. All 7 of the patients with ANLL in relapse achieved marrow hypoplasia, and 3 of them achieved complete response. LFTs were elevated in most patients but no evidence of hepatocellular necrosis was observed. It is concluded that the value of VP-16 in ANLL may have been underestimated in the past because of inadequate dosing.Abbreviations ANLL acute nonlymphocytic leukemia - CGL chronic granulocytic leukemia - DNR daunorubicin - VNC vincristine - ID Ara-C, intermediate-dose Ara-C (500 mg/m² for 12 doses) - HD Ara-C, high-dose Ara-C (3 g/m² for 12 doses) - SGGT serum glutamic transaminase - LDH lactic dehydrogenase - SGOT serum glutamic oxaloacetic transaminase     

Risk indicators for third molar caries and periodontal disease in senior adults.

PURPOSE: This study was designed to identify risk indicators for the prevalence at enrollment and incidence over 36 months of periodontal pathology and coronal caries experience affecting third molars in a community-based study of people over 65 years of age. SUBJECTS AND METHODS: Data from a subsample of 810 dentate subjects from the Piedmont 65+ Study were available for analyses. All visible teeth were examined. Periodontal probing measures were taken at 2 sites, mesiobuccal and buccal/facial. Clinical data on caries experience were collected by visual-tactile examination. At enrollment, 340 subjects had at least 1 visible third molar; all were examined for caries experience. Periodontal probing measures were available for 277 of these same subjects. The significance of the possible risk indicators for periodontal pathology and caries affecting third molars was determined by chi(2) tests. Statistical significance was set at .05. Logistic multivariable models were used to derive odds ratios and 95% confidence intervals. RESULTS: African-American subjects were more likely to have visible third molars (P < .01). Caucasian subjects were more likely to have third molar coronal caries experience (P < .01), as were subjects with greater than a high school education and those with a dental visit within 3 years (both P < .01). However, African American subjects were more likely to have periodontal pathology, CALs >/= 3 mm on third molars (P < .01), as were those who used tobacco (P < .01). None of the other risk indicators we studied were associated with progression of periodontal pathology or coronal caries experience on visible third molars. CONCLUSION: In this population study of senior adults, Caucasians and African Americans appear to have different levels of risk for caries experience and periodontal pathology affecting retained third molars.     

Integrated psychotherapeutic treatment of somatoform and other psychophysiological disorders

In this article, we have described a subgroup of patients referred from a general medical setting and suffering from a cluster of similar physical and emotional symptoms, while presenting similar psychodynamics and personality traits. In contrast to a certain scepticism in the psychiatric community about the usefulness of psychotherapy with these people, our experience suggests that when a number of diverse psychotherapeutic techniques are drawn upon in an integrated fashion, psychotherapy can be an effective clinical tool. The coping-rest model, with its combination of physiological, behavioural and dynamic approaches, has been particularly helpful. We present 3 representative cases, which reflect the overall clinical and personality features of the subgroup and the integrated psychotherapeutic approach that was utilized.     

Congenital supratentorial and infratentorial peripheral neurogenic tumor: a clinical, ultrastructural, and immunohistochemical study

Congenital neoplasms of the central nervous system are extremely rare, although they have been well documented since the earliest reports from the mid-19th century. Medulloblastoma, other primitive neuroectodermal tumors, and various types of gliomas have comprised the majority of cases. This report describes a highly unusual infratentorial and supratentorial tumor presenting as a scalp mass in a neonate who experienced in utero distress. The supratentorial mass extended through a defect in the skull to the parietooccipital lobe, and the infratentorial aspect involved the 9th and 10th cranial nerves in the region of the cerebellopontine angle. A complex spindle cell neoplasm incorporating peripheral nerve sheath and vascular characteristics was further characterized by electron microscopy and immunohistochemistry. Based upon these studies, the tumor was interpreted as a congenital schwannoma with divergent vascular differentiation. The child has been tumor-free for approximately 2 years after the initial operative procedure.