The Role of Ultrasound as a Diagnostic Tool for Sarcopenia.

Sarcopenia is the progressive loss of skeletal mass and strength, particularly in older adults, with consequent reduction in function and independence. Changing population demographics, have resulted in increased prevalence of sarcopenia and this is associated with a considerable economic burden. Whilst simple, effective, non-intrusive management of this condition exists, no routine diagnosis takes place either in the UK or in many other countries, partly due to an absence of pragmatic clinical diagnostic tools to support the early identification of the syndrome. This position paper aims to provide a short overview proposing the potential case for developing ultrasound as a new and alternative diagnostic tool for identifying sarcopenia.

HIV-AIDS in minorities.

HIV-AIDS has disproportionately affected minority populations in the United States. Significant disparities in case rates and mortality have been noted. This article reviews the magnitude of the problem and the many factors involved in the development and perpetuation of these disparities. Possible measures to help correct the problem are also reviewed.

The molecular epidemiology and drug resistance determination of HIV type 1 subtype B infection in Barbados.

To better understand the emergence of HIV-1 variants in Barbados and the association with transmission modes, we analyzed phylogenetic relationships and genetic variability among HIV-1 strains collected in 1996 from 36 antiretroviral therapy-naive patients. Only subtype B variants were present in this sampling, based on analysis of HIV-1 envelope (env) C2V3, protease (PR), and reverse transcriptase (RT) sequences. The genetic diversity of env sequences was broad (13.9%; range, 5.9-24.9%), suggesting multiple introductions of distinct HIV-1 strains to the island. The frequency of subtype B HIV-1 variants with similar env V3 features, including the tetrameric tips, GPGR and GPGK, the threonine deletion at position 23, and the substitution of threonine to arginine at position 22, was comparable in heterosexual, bisexual, and homosexual patients. Analyses of amino acid variations in PR sequences revealed a lack of major drug resistance-conferring mutations and a high (90%) prevalence of secondary mutations at positions 36, 63, 71, and 77. While the occurrence of 361, 63P, and 71T mutations in Barbadian strains was similar to the global prevalence for subtype B variants, the frequency (64%) of the V77I mutation was more than three times that seen worldwide. Only two RT antiretroviral resistance mutations (M41L and T215Y) were observed, both from a single patient. This comprehensive genetic analysis documents a broad diversity within HIV-1 subtype B in Barbados and suggests a lack of association between particular subtype B variants and transmission modes.

Chronic plasma cell pneumonia in a patient with long-standing HIV infection.

Chronic bibasilar alveolar infiltrates existed for more than 2 years in a 25-year-old woman infected with HIV for more than a decade. Bronchoscopically, there were copious, purulent secretions that grew methicillin-resistant Staphylococcus aureus (MRSA). Transbronchial biopsy specimens demonstrated plasma cell interstitial pneumonia (PCIP). Focal, transient radiographic improvement occurred after antistaphylococcal antimicrobial therapy. With recurrent and progressive symptoms, sustained clinical and radiographic improvement did not occur until corticosteroid therapy was instituted with tuberculosis chemoprophylaxis. Persistent antigenic stimulation in immunosuppressed patients causes PCIP. In this instance, the stimulus is MRSA. The previous model and support for this theory is Pneumocystis carinii. There is good experimental reason for a plasma cell response in persons infected with HIV. To our knowledge, this is the first case of chronic plasma cell interstitial pneumonia caused by indolent MRSA infection.

Hepatitis B-related polyarteritis nodosa complicated by pulmonary hemorrhage.

A 34-year-old man presented with fever, weight loss, paresthesia, abdominal pain, and hypertension. He had hepatitis B antigenemia, with negative antineutrophil cytoplasmic antibody, antinuclear antibody, and antiglomerular basement membrane serology results. Renal arteriography showed multiple intrarenal microaneurysms. In spite of therapy with antiviral agents (lamivudine, famciclovir), prednisone, cyclophosphamide, and plasmapheresis, renal function deteriorated. He later developed rapidly progressive dyspnea and hemoptysis. Diffuse alveolar hemorrhage was confirmed by bronchoscopy. He died of respiratory failure. The cause of pulmonary hemorrhage in this case of polyarteritis nodosa is unclear, but may include underlying capillaritis, cocaine-induced pulmonary hemorrhage, or recurrent attacks of malignant hypertension.

The significance of fibrin binding by plasminogen activator inhibitor 1 for the mechanism of tissue-type plasminogen activator-mediated fibrinolysis.

The specific, reversible interaction between plasminogen activator inhibitor 1 (PAI-1) and intact fibrin polymers was studied using both purified components and isolated activated platelets as a source of PAI-1. A key reagent in these experiments is a PAI-1 mutant, having its P1 reactive center residue arginine replaced by methionine (PAI-1 R346M). The second-order association rate of PAI-1 R346M with tissue-type plasminogen activator is over 10,000-fold lower than that of wild-type PAI-1, whereas the ability of the variant to bind to fibrin is unaltered. Competition experiments demonstrated that PAI-1 R346M is equally effective as wild-type PAI-1 in displacing 125I-labeled PAI-1 from fibrin. Fibrinolysis, mediated by tissue-type plasminogen activator, is inhibited in a dose-dependent manner by purified PAI-1. The inhibition can be relieved in a dose-dependent manner by PAI-1 R346M, presumably due to displacement of wild-type PAI-1 by PAI-1 R346M. Perfusion studies, using platelet-rich clots, revealed that the incorporation of PAI-1 R346M dose dependently decreased the 50% clot lysis time. These data indicate that PAI-1 R346M displaces fibrin-bound, endogenous PAI-1 released from activated platelets. Implications to manipulate PAI-1 activity for the management of clinical complications, in particular reocclusion after thrombolytic therapy, are discussed.

The role of the finger domain of tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor 1 (PAI-1) in initiation and progression of thrombolysis.

We further investigated the role of the finger (F) and the kringle-2 (K2) domains of tissue-type plasminogen activator (t-PA) in fibrin-stimulated plasminogen activation. To that end, the action of purified (wt) t-PA or of variants lacking F (del.F) or K2 (del.K2) was assessed either in a static, human whole blood clot-lysis system or in whole blood thrombi generated in the "Chandler loop". In both clot-lysis systems, significant differences were observed for the initiation of thrombolysis with equimolar concentrations of the t-PA variants. A relatively minor "lag phase" occurred in thrombolysis mediated by wt t-PA, whereas a 6.4-fold and 1.6-fold extension is found for del.F and del.K2, respectively. We observed identical lag-times, characteristic for each t-PA variant, in platelet-rich heads and in platelet-poor tails of thrombi. Since plasminogen activator inhibitor 1 (PAI-1) is preferentially retained in the platelet-rich heads, we conclude that the inhibitor does not interfere with the initial stage of thrombolysis but exerts its action in later stages, resulting in a reduction of the rate of clot lysis. A complementation clot-lysis assay was devised to study a potential interplay of del.F and del.K2. Accordingly, clot lysis was determined with combinations of del.F and del.K2 that were inversely varied in relation to equipotent dosage to distinguish between additive, antagonistic or synergistic effects of these variants. The isobole for combinations of del.F and del.K2 shows an independent, additive action of del.F and del.K2 in clot lysis.(ABSTRACT TRUNCATED AT 250 WORDS)

Plasminogen activator inhibitor-1 released from activated platelets plays a key role in thrombolysis resistance. Studies with thrombi generated in the Chandler loop.

To investigate the potential role of plasminogen activator inhibitor-1 (PAI-1), which is released from the alpha-granules of activated platelets, in thrombolysis resistance, we employed a model (the "Chandler loop") that mimics the formation of arterial thrombi in vivo and that can be manipulated in terms of rheological parameters and composition of blood cells. Light and electron microscopy revealed that the distribution of blood cells in Chandler thrombi is polarized, as it is in arterial thrombi, resulting in platelet-rich "white heads" and red blood cell-rich "red tails.". Resistance toward tissue-type plasminogen activator (TPA)-mediated thrombolysis parallels the presence of platelets that are fully activated in this system. We demonstrate that the PAI-1 released by the alpha-granules is preferentially retained within the thrombus and that the concentration of PAI-1 antigen is higher in the head than in the tail of the thrombus. The relative thrombolysis resistance of the heads of Chandler thrombi can be largely abolished by inclusion of an anti-PAI-1 monoclonal antibody that blocks that inhibitory activity of PAI-1 toward TPA. We propose that PAI-1, released from activated platelets, plays a key role in thrombolysis resistance and/or reocclusion after thrombolytic therapy. This is due to binding of PAI-1 to polymerized fibrin within the thrombus, followed by inhibition of TPA-mediated fibrinolysis.

Sitosterolaemia and heterozygous familial hypercholesterolaemia in a three year old girl: case report.

A case of a 3 1/2 year old female child is described in which symptomless cutaneous xanthomatosis led to the diagnosis of sitosterolaemia in the presence of a defect of low-density lipoprotein uptake by cultured fibroblasts. The condition responded to treatment by cholestyramine with normalisation of the blood lipid levels. Normal growth and development continued for three years of observation.

Tetracycline and minocycline in the management of non-gonococcal urethritis: a comparison.

A clinical trial compared the relative efficacy of tetracycline hydrochloride 250 mg qid and minocycline hydrochloride 100 mg bid given for an initial period of ten days to 59 patients suffering from non-gonococcal urethritis (NGU). Those patients with persistent symptoms or signs on completion of the initial course were given a second course for a further ten days at the same dosage. The treatments were equivalent. A significant number of patients not clinically cured after one course of treatment responded satisfactorily to a second course.

A multicentre trial of Zostrum (5 percent idoxuridine in dimethyl sulphoxide) in herpes zoster.

Forty-six patients with herpes zoster were randomised into two groups treated with DMSO alone and 5 percent IDU in DMSO, provided that treatment started within 48 hours of the appearance of a rash. In the IDU group the interval before pain improved was significantly shorter than in the control DMSO group, and significantly fewer new vesicles developed at the three day follow up in the active group compared with the control group. These findings are in agreement with previously published work and confirm the usefulness of Zostrum (5 percent IDU in DMSO) in the treatment of herpes zoster.

The virus of hepatitis B a new dimension in the diagnosis of sexually transmitted disease.

Ten patients presenting with venereal or dermatological disorders have been found to have evidence of infection with the virus of hepatitis B; only five had distinguishable liver dysfunction, yet all had either detectable antigen or antibody. Antigen subtype ayw has been identified in four of these people. Once rare in the local population, hepatitis B virus infection appears to be increasing in incidence with cases attributable to inoculation and to direct contact, as well as presenting as a covert partner to gonorrhoea, urethritis and candidiasis. Testing for hepatitis B antigen and antibody is recommended for patients attending the venereal diseases clinic, for patients presenting for removal of tattoos, for those with suspected drug taking and for Polynesians, in whom the carrier rate may be expected to be high (Austin and others, 1974). In our current clinical practice the sterilisation of instruments, the handling of patients, and the transmission of specimens to the laboratory have been reviewed in the light of the US Public Health Service supplement 1976, Perspectives on the Control of Viral Hepatitis, Type B.