Antenatal Screening for HPA-la by Flow Cytometry

Summary: regnant women who attended antenatal clinics at King George V Hospital, the Birth Centre or were referred by obstetricians from February to July. 1996 were screened for the platelet antigen HPA-la by flow cytometry. Forty out of 2300 (1.7%) were found to be negative for this antigen . Of the 28 women followed throughout their pregnancy, none developed antibody to HPA-la. Platelet counts performed on samples from 17 babies born to 17 of these mothers were all normal. This study proves the simplicity and rapidity of flow cytometry for platelet antigen screening. The results were comparable with the Solid Phase Red Cell Adherence (SPRCA) method and with PCR. The lack of a plentiful supply of specific antibody and the rarity of fetomaternai alloimmune thrombocytopenia (FMAIT) argue against the introduction of routine screening for maternal HPA-la status at the present time.     

Nephrectomy during operative management of retroperitoneal sarcoma

Background: Complete resection of a retroperitoneal sarcoma often requires removal of adjacent organs. In this study we evaluated the role of nephrectomy during operation for retroperitoneal sarcoma. Methods: Between July 1982 and July 1995, 75 of the 371 (20%) patients who underwent resection of retroperitoneal sarcoma at MSKCC underwent concommitant nephrectomy. Data concerning the reasons for nephrectomy, degree of sarcomatous renal involvement, and survival were retrospectively analyzed. Results: Fifty-four patients (72%) underwent nephrectomy during the initial resection, and 21 (28%) during a resection of a recurrent or persistent tumor. The most common reason for nephrectomy was total encasement by sarcoma (n=40; 53%), followed by dense adherence of the tumor to the kidney (n=21; 28%), and the direct invasion of the kidney by tumor (n=2; 3%). Pathology demonstrated an absence of kidney invasion in the majority of cases (55 of 75; 73%). Renal capsular invasion was present in 11 of 75 (15%), renal parenchymal invasion in 7 of 75 (9%), and renal vein invasion in 2 of 75 (3%) of cases. There were no significant differences in survival based on degree of sarcoma involvement of the kidney, tumor grade, or whether the resection was for primary or recurrent disease. The 53 patients who underwent a complete gross resection of all tumor had a significantly improved long-term survival compared to the 20 patients who did not (50% versus 20% DFS at 5 years, respectively; p<0.001). Conclusions: Decisions for concomitant nephrectomy during resection of retroperitoneal sarcoma should be based on whether this maneuver will provide a complete resection of all gross tumor, in which case the long-term disease-free survival of 50% is comparable to the reported 5-year survival of all patients with retroperitoneal sarcoma who are completely resected. Presented at the 49th Annual Cancer Symposium of the Society of Surgical Oncology, Atlanta, Georgia, March 21–24, 1996.     

Noninvasive Estimation of Blood Alcohol Concentrations: Ethanol Vapor Above the Eye

The present study describes, in animals, a novel approach to the in vivo, noninvasive determination of alcohol in the body. The concentration of ethanol in vapor above the lacrimal fluid in the eye was analyzed in situ by the use of a fast (1-min) gas sensor method developed previously for biological liquids. After an oral dose of 1 g/kg to 11 animals, eye vapor measurements and blood samples were obtained over 4 hr. The correlation of 61 blood ethanol concentrations obtained by the two methods yielded a correlation coefficient of 0.92 and a slope of 0.99. The metabolic rates of ethanol determined by gas chromatographic analysis of blood and by ethanol eye vapor analysis are virtually identical. The data suggest that ethanol eye vapor analysis may be an attractive, noninvasive method for the determination of ethanol in animals. The method is not subject to false high readings due to alcohol in the buccal cavity and thus might constitute an alternative to breath analysis in the human. In a separate series, ethanol was determined by head space gas chromatography in samples of blood and lacrimal fluid while the animals were under ketamine anesthesia. The correlation of ethanol concentrations in blood and lacrimal fluid (r = 0.99) shows that ethanol is distributed in lacrimal fluid which comprises part of total body water.     

'Not everything that can be counted counts and not everything that counts can be counted'– towards a critical exploration of modes of satisfaction measurement in sheltered housing

This paper reflects on a research project funded by a consortium of leading sheltered housing (SH) providers and their regulatory body, the Housing Corporation. The project aimed to ascertain which aspects of SH older people perceived to be central to their satisfaction and the methods they judged most appropriate to measuring this. We outline key policy developments of importance to SH (specifically the development of performance measurement regimes), and changes in the nature of SH, which are driving providers to re‐evaluate how they measure user satisfaction. We discuss the aims of the project, our methodology and findings, and conclude by raising critical questions about the process of measuring satisfaction within an increasingly managerialised housing system. We argue that this favours standardised methods of information gathering (such as questionnaires) rather than engage with clients in order to develop methods and systems capable of eliciting qualitative issues of concern to them. Our conclusions are, we believe, applicable to health and social care provision, where similar tensions exist around performance measurement and user satisfaction.     

Combined Excimer Laser and Topical Tacrolimus for the Treatment of Vitiligo: A Pilot Study

Background. Vitiligo is an acquired skin disorder that is characterized by well-defined, often symmetric white patches. Although current therapeutic modalities are directed toward increasing melanocyte melanin production, few treatment modalities address the immunologic nature of the disease.
Objective. To determine whether excimer laser, a known therapeutic modality, in combination with tacrolimus, a topical immunomodulator, accelerate response time and/or improve the degree of response in patients with this disorder.
Methods. Eight subjects diagnosed with vitiligo were recruited to participate in this institutional review board–approved double-blind, placebo-controlled study. Twenty-four symmetric vitiliginous patches (elbows, knees) from eight subjects received excimer laser treatment three times per week for 24 treatments or 10 weeks. Additionally, topical tacrolimus 0.1% ointment (Protopic) and placebo (Aquaphor) were applied to randomized patches (left or right) twice daily throughout the length of the trial. Vitiliginous patches were monitored with photographs at baseline, every 2 weeks, and 6 months after treatment. Biopsies were performed on subjects with significant results.
Results. Twenty vitiliginous patches from six subjects qualified for evaluation. Fifty percent of patches treated with combination excimer laser and tacrolimus achieved a successful response (75% repigmentation) compared with 20% for the placebo group. Subjects who responded successfully repigmented faster (19%) with combination therapy compared with excimer laser alone. Additionally, three subjects experienced transient hyperpigmentation in lesions treated with combination therapy.
Conclusion. Combining topical immunomodulators with known phototherapeutic modalities may represent a key advancement in the treatment of disease.     

Extended HLA profile of an inbred isolate: The Schmiedeleut Hutterites of South Dakota

HLA-A, -B, -C, -DR, and -DQ typings of the Schmiedeleut Hutterites of South Dakota were collected as part of an ongoing genetic-epidemiologic study of HLA and fertility. A total of 1,082 individuals, including 852 married adults representative of the reproductive population of this isolate, were characterized for five-locus HLA haplotypes. HLA-A1, A2, A3, and A24 accounted for 75% of observed HLA-A alleles and HLA-B27, B35, B51, and B62 accounted for 55% of observed HLA-B alleles. S-leut Hutterites are derived from 68 or fewer ancestors. However, only 48 ancestral HLA haplotypes were observed and nine of these accounted for over 52% of the observed haplotypes. Measures of two-locus linkage disequilibrium derived from these haplotypes indicated that one-third to half of the observed HLA-A/B, B/DR, and A/DR allele combinations exhibited highly statistically significant linkage disequilibrium. Allele and haplotype frequencies did not differ between males and females. Recombination rates of 0.004% and 0.005% between HLA-A and -C and between HLA-B and -DR, respectively, were observed. This HLA profile points out a paucity of HLA alleles and haplotypes in this population and marked linkage disequilibrium among the HLA alleles that are present. © Wiley-Liss, Inc.     

The G-protein-coupled receptor kinases beta ARK1 and beta ARK2 are widely distributed at synapses in rat brain.

The beta-adrenergic receptor kinase (beta ARK) phosphorylates the agonist-occupied beta-adrenergic receptor to promote rapid receptor uncoupling from Gs, thereby attenuating adenylyl cyclase activity. Beta ARK-mediated receptor desensitization may reflect a general molecular mechanism operative on many G-protein-coupled receptor systems and, particularly, synaptic neurotransmitter receptors. Two distinct cDNAs encoding beta ARK isozymes were isolated from rat brain and sequenced. The regional and cellular distributions of these two gene products, termed beta ARK1 and beta ARK2, were determined in brain by in situ hybridization and by immunohistochemistry at the light and electron microscopic levels. The beta ARK isozymes were found to be expressed primarily in neurons distributed throughout the CNS. Ultrastructurally, beta ARK1 and beta ARK2 immunoreactivities were present both in association with postsynaptic densities and, presynaptically, with axon terminals. The beta ARK isozymes have a regional and subcellular distribution consistent with a general role in the desensitization of synaptic receptors.     

Use of calcium alginate to pack abscess cavities: a controlled clinical trial.

Many conventional dressings are painful when removed, and may be detrimental to healing. In a pilot study ten consecutive abscesses, requiring incision and drainage, were packed with a calcium alginate dressing: this was well tolerated, its removal causing minimal pain. No adverse effects were attributable to its use. A controlled trial was therefore carried out to compare calcium alginate with the more traditional saline-soaked gauze for packing abscess cavities, following incision and drainage. Patients were randomized to receive either calcium alginate (16 patients) or gauze dressing (18 patients). At the first dressing change the patient marked on a linear analogue scale the pain experienced; the nurse noted similarly the ease of removal of the dressing. Calcium alginate was significantly less painful to remove after operation (P less than 0.01), and also easier to remove (P less than 0.01) than gauze dressings. If abscess cavities are packed after incision and drainage, calcium alginate appears to be an improvement on conventional dressings.     

Detection and partial purification of a potent mitogenic factor for human thyroid follicular cells.

Normal adult human thyroid follicular cells have an extremely limited proliferative capacity in vitro. No previously studied mitogen, including thyrotropin (TSH) or epidermal growth factor (EGF), has in our hands resulted in a significant improvement over the 3-4% nuclear [3H]thymidine pulse-labelling index (LI) obtainable with 10% fetal calf serum. Here we report the detection in the conditioned medium from a sub-clone of NIH3T3 fibroblasts of a mitogenic activity capable of increasing this response up to 10-fold, to an LI of over 20%, together with an even greater relative stimulation of mitotic activity. Preliminary characterisation has excluded EGF and TGF alpha, and demonstrated that the activity is bound reversibly by heparin-Sepharose, thus pointing to a member of the heparin-binding fibroblast- or hepatocyte-growth factor families. This material should have wide practical application in facilitating primary culture of follicular cells, and may reveal new mechanisms of stromal-epithelial interaction regulating normal and neoplastic thyroid growth in vivo.