Immunohistochemical analysis of the stage-specific expression of Ia antigens in the rat mammary gland during pregnancy and lactation

The expression of Class II MHC antigens in the rat mammary gland was assessed by immunoperoxidase using monoclonal antibodies against rat homologues of the murine I-A and I-E antigens. Our results showed that, while I-A and I-E were inconspicuous in undifferentiated mammary epithelium in virgin rats, during early pregnancy, the ductal epithelium becomes intensely positive for both antigens. A monoclonal antibody specific for macrophages showed that they were abundant in the stroma but did not correspond to the epithelial staining. During late pregnancy and lactation, the ductal epithelium expressed varying levels of Ia, while the alveolar epithelial cells were consistently Ia-negative. Ia-positive mononuclear cells of round or dendritic morphology present in the alveolar areas were enumerated as cells per high power field (HPF). Maximal cell counts for I-A and I-E were seen in late pregnancy and early lactation, with a significant decline in mid-lactation. Counts were higher in intraepithelial locations than in the subjacent connective tissue at all stages. The possible role of these stage-specific alterations in regulating local immune responses and transfer of immune components into milk is discussed.     

Retrospective study of the management of chemotherapeutic extravasation injury

Despite the now widespread experience with the administration of chemotherapeutic agents in oncology, extravasation injuries still occur. Furthermore, the most appropriate management of such injuries is not known. The authors examined the current treatment options for extravasation injury and the incidence of this problem. All cases of extravasation referred to the plastic surgery service at one institution from 1994 through 1996 were examined. During a 6-year period there were 44 cases of extravasation injury identified in 42 patients. Comparison with a previous study conducted 15 years before at the same institution revealed a significant reduction in the incidence of extravasation injuries during that time (0.01% vs. 0.1%; = 0.00). The site of extravasation was peripheral in 32 cases and central in 12. Paclitaxel and doxorubicin were the two most common drugs involved. The local infusion of antidotes was not performed routinely. Only 26 of the 42 patients were referred to the plastic surgery service for care. Only 10 of those 26 patients required local ulcer excision and closure to achieve a healed wound. The mean time between injury and referral was 40 days. This time did not predict the subsequent need for a surgical procedure. Most patients, including the remaining 16 referred to the plastic surgery service, did not require surgical intervention. All were watched expectantly, and their injuries healed spontaneously. In conclusion, the incidence of extravasation is decreasing, most likely as a result of the diligence in the administration and identification of extravasation injuries as well as the result of the use of more central infusion sites. Most cases can be managed conservatively, with directed surgical treatment of the ulceration when appropriate.     

Interactions of cyclosporines with lipid membranes as studied by solid-state nuclear magnetic resonance spectroscopy and high-sensitivity titration calorimetry

Cyclosporin A (CyA) interacts with lipid membranes. Binding reaction and membrane location of CyA and analogs were examined with 2H-NMR, high-sensitivity isothermal titration calorimetry (ITC), and CD spectroscopy. Effects of CyA and charged analogs on the phosphocholine head group and on the membrane interior were investigated using selectively deuterated phospholipids. Incorporation of cyclosporin generated small disordering of the lipid acyl chains. Binding of CyA and neutral and positively charged analogs to lipid membranes showed endothermic heats of reaction between + 5.9 and + 11.3 kcal/mol, whereas enthalpy of binding was close to zero for the negatively charged derivative. Binding constants of cyclosporines to liposomal membranes were in the range of K(P) = 1650-5560 M(- 1) depending on the cholesterol content. (2)H-NMR provides evidence that CyA is essentially located in the interior of the bilayer membrane. For the charged analogs an additional interaction occurs at the head group level, placing the polar groups of these CyA analogs in the vicinity of the phosphocholine dipoles. The association of CyA and its analogs is accompanied by a positive enthalpy change, which is overcompensated by positive entropy changes. Binding of CyA to lipid membranes thus follows the classical hydrophobic effect, which is in contrast to many other peptide-lipid binding reactions.     

Determinants of physician unwillingness to offer medical abortion using mifepristone.

PURPOSE: We sought to identify factors associated with contemplating versus not contemplating offering medical abortion with mifepristone among physicians not opposed to it. METHODS: We analyzed data from a Kaiser Family Foundation survey of a nationally representative sample of 790 American obstetrician/gynecologists and primary care physicians. Our study sample consisted of 419 physicians who were not personally opposed to medical abortion and could be classified as not actively considering (precontemplation) or actively considering (contemplation) offering mifepristone. We conducted multivariate logistic regression to predict being unlikely to offer mifepristone (i.e., in the precontemplation stage of change). PRINCIPAL FINDINGS: In 2001, 1 year after U.S. Food and Drug Administration (FDA) approval, 5% of physicians surveyed were offering mifepristone. Among the 750 physicians not offering mifepristone, 57% were not opposed. Of those not opposed, 74% reported that they were unlikely to offer mifepristone in the next year (precontemplation) as compared to 23% who might offer it (contemplation). Independent predictors of being in the precontemplation stage were being a primary care versus OB/GYN physician (odds ratio [OR] 3.29, p = .02), being in private versus hospital-based practice (OR 2.40, p = .03), and lacking concerns about FDA regulations (OR 2.06, p = .01) or violence and protests (OR 1.93, p = .03) as barriers to offering mifepristone. CONCLUSIONS: For precontemplation-stage physicians, the most efficient strategy for increasing the availability of medical abortion may be to design programs that emphasize clinical benefits and feasibility to stimulate interest in the procedure. For contemplation-stage physicians, the optimum approach may be one that helps to overcome barriers associated with FDA regulations and concerns about violence and protests.     

Serial proton MR spectroscopy of contrast-enhancing multiple sclerosis plaques: absolute metabolic values over 2 years during a clinical pharmacological study

BACKGROUND AND PURPOSE: The time courses of total creatine (Cr), N-acetylaspartate (NAA), choline (Cho), and myo-inositol have not previously been investigated in the follow-up of contrast-enhancing multiple sclerosis (MS) plaques. Therefore, over a period of 2 years, we compared the absolute concentrations of these metabolites between patients treated with a placebo or 15 +/- deoxyspergualin (DSG) and between clinical groups with relapsing-remitting or secondary-progressive MS. METHODS: Sixteen patients, recruited from a pharmacological study of DSG, and 11 healthy control subjects were investigated by a stimulated-echo acquisition mode sequence (TR/TE = 3000/20). The selected volume initially contained a contrast-enhancing plaque, which was followed up for a period of 2 years. RESULTS: In contrast-enhancing plaques, Cho was significantly elevated and showed a significant reduction after both 3 and 12 months. The initially normal Cr significantly increased between 3 and 12 months, and was negatively correlated with plaque volume on T1-weighted MR images. NAA initially showed normal values, a significant decrease at 1 month, and a slow recovery over 2 years. Myo-inositol did not show a clear tendency. The placebo group did not differ from the treated group, nor did the relapsing-remitting group differ from the secondary-progressive group. CONCLUSION: The contradictory time courses of Cr and NAA show that an absolute quantification in proton MR spectroscopy in MS is necessary to avoid a false interpretation of reduced NAA/Cr ratios. The increase in Cr is probably due to remyelination. The initial dip and later recovery of NAA seem to be related to diminishing edema and remyelination.     

Auditory cortical responses in hearing subjects and unilateral deaf patients as detected by functional magnetic resonance imaging

Functional magnetic resonance imaging is a non-invasive method for the detection of focal brain activity at high spatial resolution. Acoustic stimulation leads to a blood oxygenation level dependent signal change in the plane of the superior temporal gyrus. The dependence of this response in the auditory cortex on binaural, monaural left and monaural right acoustic stimulation for 10 healthy subjects and five monaural deaf patients is described. Acoustic stimulation consists of 1000 Hz pulsed sine tones at a pulse rate of 6 Hz and a sound pressure level of 95 dB. For monaural stimulation, normal-hearing subjects revealed a strong lateralization of cortical response towards the contralateral hemisphere. The lateralization ratios between left and right hemispheric response areas were 3.4-5.2 for monaural stimulation and nearly balanced for binaural stimulation. Additionally, the sum of cortical activation volumes induced by monaural left and right stimulation was approximately 30% smaller than for binaural stimulation, indicating either inhibitory mechanisms or neuronal facilitation within the auditory pathways. For monaural deaf subjects the lateralization ratio between left to right response was just 1.3 towards the contralateral hemisphere of the healthy ear, which is comparable to binaural responses of normal-hearing subjects. This observation seems to indicate a plasticity or a reorganization of auditory pathways of monaural deaf patients.      

替硝唑软膏的研制与临床应用

目的:研究替硝唑软膏,并应用于临床。方法:参照同类制剂,确定最优组方和制备方法,采用紫外分光光度法测定含量,用比较法进行临床疗效观察。结果:制剂制备简单,含量测定方法简便,结果可靠,经临床应用牙周炎、牙龈炎患者62例,总有效率95.3％。结论:本品是治疗牙周炎、牙龈炎的理想制剂,值得推广应用。     

Pilot study of d-penicillamine, vitamins and minerals in multiple sclerosis

A pilot study of the effect of D-penicillamine in multiple sclerosis (MS) was undertaken because of D-penicillamine's activity against RNA neurotropic viruses, because it is effective against the auto-immune disease, rheumatoid arthritis, and because both viruses and autoimmunity have been implicated in multiple sclerosis. We have treated 16 patients with advanced MS, nine on full doses (2-2.25 grams/day) and seven whose treatment was permanently stopped for reasons other than adverse reactions. There has been some improvement in most of those whose treatment was not withdrawn, and no change or deterioration in those not continued on the therapeutic regimen. Despite use of a high dosage regimen, such as has evoked intolerable side effects in a high percentage of patients with rheumatoid arthritis, we have experienced few side effects in a total of 48 patients suffering from diseases with auto-immune components, a finding we speculate is due to replacement of nutrients inactivated or removed by D-penicillamine, and to supplementation with selected nutrients.     

Brain tumors: MR imaging with gadolinium-DTPA

Magnetic resonance (MR) imaging was performed on 40 patients with intracranial tumors, before and after intravenous administration of gadolinium-DTPA (Gd-DTPA). Precontrast studies included a comprehensive protocol of spin-echo sequences. Tumors were visualized on precontrast images either directly or indirectly by anatomic distortion caused by the mass. However, differentiation of the tumor from adjacent tissues was possible in only 17 of 40 cases. Delineation of the tumor was best on precontrast, T2-weighted images. After administration of Gd-DTPA (0.1 mmol/kg), increased signal intensity from the tumor was observed in all patients. The localized increase in signal intensity in the tumor considerably improved the tumor delineation in 36 of 40 patients. Whereas most of the meningiomas, neuromas, and adenomas could be delineated prior to administration of contrast material if appropriate pulse sequences were applied, glioblastomas and intracranial metastases required Gd-DTPA administration for diagnostically sufficient tumor display.