Viral dynamics of primary viremia and antiretroviral therapy in simian immunodeficiency virus infection

Mathematical modeling of viral replication dynamics, based on sequential measurements of levels of virion-associated RNA in plasma during antiretroviral treatment, has led to fundamental new insights into human immunodeficiency virus type 1 pathogenesis. We took advantage of the simian immunodeficiency virus (SIV)-infected macaque model to perform detailed measurements and mathematical modeling during primary infection and during treatment of established infection with the antiretroviral drug (R)-9-(2-phosphonylmethoxypropyl)adenine (PMPA). The calculated clearance half-life for productively infected cells during resolution of the peak viremia of primary infection was on the order of 1 day, with slightly shorter clearance half-lives calculated during PMPA treatment. Viral reproduction rates upon discontinuation of PMPA treatment after 2 weeks were approximately twofold greater than those obtained just prior to initiation of treatment in the same animals, likely reflecting accumulation of susceptible target cells during treatment. The basic reproductive ratio (R0) for the spread of SIV infection in vivo, which represents the number of productively infected cells derived from each productively infected cell at the beginning of infection, was also estimated. This parameter quantifies the extent to which antiviral therapy or vaccination must limit the initial spread of virus to prevent establishment of chronic disseminated infection. The results thus provide an important guide for efforts to develop vaccines against SIV and, by extension, human immunodeficiency virus.     

Bronchiolo-alveolar cell carcinoma with apparent response to chemotherapy to anti-tuberculosis

Pigmented vulvar lesions were observed in a child during a sexual abuse evaluation. Gross examination of the lesions appeared most consistent with bowenoid papulosis; however, biopsy confirmed the lesions to be pigmented apocrine hamartomas. To our knowledge, these rare and benign tumors have never been described as pigmented, but should be added to the differential diagnosis of pigmented vulvar lesions.     

Polymeric prodrugs of mitomycin C designed for tumour tropism and sustained activation

Prodrugs of mitomycin C (MMC) based on soluble poly-[N-(2-hydroxyethyl)-L-glutamine] (pHEG) polymers have been evaluated as tumour-targeted drugs. These materials are designed to exploit the enhanced permeability of tumour vasculature, combining a passive tumour tropism with decreased systemic liberation of free MMC. A tri- or tetrapeptide linkage (e.g. Gly-Phe-Ala-Leu) between pHEG and the aziridine nitrogen of MMC can combine good hydrolytic stability with rapid cleavage by lysosomal enzymes, releasing free MMC. The conjugates showed decreased systemic toxicity and could be administered to mice at a total MMC dose of 15 mg/kg i.v., compared with just 6 mg/kg for free MMC. Conjugates also showed better activity against animal models of established tumours, achieving up to 77% increased life span (ILS) against solid P388 leukaemia, compared with only 23% for free MMC, and up to 121% ILS against solid C26 colorectal carcinoma, compared with no activity for the free drug. Improving the therapeutic index of anticancer drugs by combining tumour tropism with decreased systemic toxicity is a versatile approach that should produce a new generation of improved anticancer agents.     

Impact of crosstalk in an arrayed-waveguide multiplexer onN×N optical interconnection

The impact of crosstalk in an arrayed-waveguide N×N wavelength multiplexer is investigated precisely in relation to its application to wavelength-routing N×N all optical networks. In such systems multiple crosstalk light which has the same wavelength as the signal results in signal-crosstalk beat noise. We confirm that the noise is Gaussian and obtain the relation between crosstalk and power penalty. It is shown that the crosstalk must be less than -38 dB for a 16×16 system to keep the power penalty below 1 dB at a bit error rate of 10^-9     

Complications of chronic otitis media

In summary, recent literature indicates that the complications of chronic otitis media have been decreasing. However, even with the advent of modern and more powerful antimicrobials and aggressive surgical eradication of disease, the morbidity and mortality are still high. Some complications may initially be quite obvious and some complications may be quite subtle. Therefore, the most important tools in making early diagnosis are careful history and physical examination, and a high index of suspicion for impending complications.     

Increasing the service properties of weld joints by electrohydroimpulse treatment

Known examples of the positive influence of electrohydroimpulse treatment on the quality of weld joints of various steels, particularly including an increase in their long-term and cyclic strength and also corrosion resistance, are analyzed. It is shown that in this case there is a reduction in residual macro- and micro-stresses and also a change in the parameters of the dislocation structure of the joint metal in the direction of stabilization of it.Translated from Problemy Prochnosti, No. 4, pp. 119–123, April, 1996.     

Radiation therapy of giant aggressive keratoacanthomas

BACKGROUND AND DESIGN: Giant aggressive keratoacanthoma is a rare destructive subset of keratoacanthoma that frequently involves the facial region, grows rapidly to a large size, and often recurs after surgical management. The effectiveness of ionizing radiation therapy was examined in a retrospective study involving 16 patients; 14 of the tumors had recurred after surgical therapy. RESULTS: All tumors resolved with satisfactory cosmetic results and without recurrence following a fractionated course of superficial radiation therapy. CONCLUSIONS: Radiation therapy is an effective therapeutic modality for giant aggressive keratoacanthomas.