Simultaneous determination of the new HIV protease inhibitor lopinavir (ABT 378) and of indinavir(1), amprenavir, saquinavir, ritonavir (ABT 538)(2) and nelfinavir(3) in human plasma by gradient HPLC.

Protease inhibitors are known by their inhibition of a viral protease that leads to production of immature and non-infectious virus particles. The novel protease inhibitor KALETRA is a co-formulation of lopinavir and ritonavir. Ritonavir reduces the metabolization of lopinavir by the cytochrome P450 3A4 isoenzyme which leads to markedly increased plasma levels of lopinavir(4). A new rapid and sensitive HPLC method for the simultaneous determination of lopinavir, indinavir, amprenavir, saquinavir, ritonavir and nelfinavir in human plasma has been developed. An aliquot of 500 microl plasma, spiked with internal standard, was extracted with 500 microl 0.1 M ammonium hydroxide solution and 5 ml tert. -butyl ether. After drying under a nitrogen stream, the residue was redissolved in an eluent consisting of 50 mM phosphate buffer, pH 5.40 and acetonitrile (50:50, v/v). Chromatographic separation was accomplished on a C-18 column using a non-linear gradient elution and ultraviolet detection at 215 nm.

[Women and AIDS. HIV-positive patients need special monitoring]. / Frauen und AIDS. HIV-positive Patientinnen brauchen eine besondere Betreuung.

Worldwide, 50% of all HIV-positive persons are female. The situation is particularly dismal in Africa and Asia, in South America and in the Caribbean. Germany is confronted with a high percentage of immigrants from countries in these parts of the world, and consequently must expect to see an increasing rate of HIV-positive women from these regions. This makes programs for the management of female HIV-positive victims an urgent necessity. The present article describes a multidisciplinary concept, whose aim it is, via comprehensive preventive measures, to avoid medium- and long-term complications.

[Stopping secondary prevention in AIDS patients with inactive CMV retinitis treated with HAART (highly active antiretroviral therapy)]. / Absetzen der Sekundärprophylaxe bei Aids-Patienten mit inaktiver CMV-Retinitis unter HAART.

BACKGROUND: Immune recovery of AIDS patients with cytomegalovirus (CMV) retinitis treated and healed by highly active antiretroviral therapy (HAART) is reflected by increased CD4 cell count and decreased virus load. Due to partial reconstitution of the immune status the risk of opportunistic infections decreases, as well as the risk of reactivating inactive CMV retinitis. It may therefore be possible to stop anti-CMV maintenance therapy may after HAART-induced immune recovery. PATIENTS AND METHODS: We present six patients (nine eyes) with a follow-up of 9.5 months (range 7-12 months) after cessation of the CMV-specific maintenance therapy (five orally, one intravenously). RESULTS: There was no reactivation of retinal CMV infection during the follow-up period. The virus load (< 50 Eq/ml; a single value of one patient was 2047 Eq/ml) and CD4 cell counts (range 207-454/microliter; mean: 313/microliter) remained stable during the follow-up period, reflecting immune recovery. CONCLUSIONS: Our findings confirm the expected low risk of retinal CMV reactivation after immune recovery in AIDS patients receiving HAART without secondary prophylaxis with an anti-CMV maintenance therapy. Regular ophthalmic and medical follow-up is mandatory in these patients. Cessation of maintenance therapy represents a major improvement in quality of live in AIDS patients.

[Progressive cicatricial psoriatic alopecia in AIDS]. / Progressive vernarbende psoriatische Alopezie bei Aids.

Scarring alopecia is a rare complication of scalp psoriasis which in most cases occurs in areas of long-standing lesions. A HIV-positive 35 year-old Moroccan patient (CDC C3) developed scalp psoriasis with scarring alopecia within five weeks. Topical antipsoriatic therapy resulted in alleviation of psoriatic lesions and stopped the progression of the alopecia. This case report suggests potential pathogenic links between scalp psoriasis, scarring alopecia, and HIV-infection. In addition, early and efficient antipsoriatic treatment is recommended to prevent the disfiguring complication of scarring alopecia.

Anal endosonography and manometry: comparison in patients with defecation problems.

PURPOSE: Correlations between anal sphincter function as assessed by anorectal manometry and anal sphincter anatomy measured by endoluminal ultrasound have been reported in the literature both for patients and for healthy individuals but have not been confirmed by other authors. METHODS: For a larger series of patients (152 consecutive patients, mean age 54.1 +/- 15.5 years; female:male ratio, 111:41) with anorectal dysfunctions such as incontinence (n = 92), constipation (n = 37), and other symptoms (n = 23), diagnostic work-up included conventional multilumen anorectal manometry to evaluate internal sphincter pressure at rest, maximum external sphincter squeeze pressure during contraction, and endoanal sonography to determine anal sphincter integrity and to measure dorsal, left lateral, and right lateral diameter of the internal anal sphincter (IAS) and external anal sphincter (EAS) muscles. RESULTS: Maximum squeeze pressure was significantly correlated to muscle thickness of the EAS (P = 0.001). No association was found between resting pressure and IAS diameter. Women had significantly lower resting and squeeze pressures than men (P = 0.008 and P = 0.003, respectively), but age-related changes of function were only found for resting pressure. Endosonographic values of IAS and EAS did not differ between genders but were significantly correlated with age (P = 0.008 and P = 0.02, respectively). Because all correlations were rather weak, they only can explain a small portion of data variance. CONCLUSION: Anal manometry and anal ultrasound, therefore, are of complementary value and are both indicated in adequate clinical problems.

How reproducible are measures of the anal sphincter muscle diameter by endoanal ultrasound?

UNLABELLED: Anal endosonography is an imaging technique for the anal sphincter system and offers analysis of its muscular integrity. It is generally assumed that measurement of the thickness of muscle layers is provided by sonography; however, reproducibility of such measurements have not yet been investigated. METHODS: Study 1: In 10 healthy volunteers, endoanal ultrasound was performed independently by two experienced investigators with two different ultrasound machines, and thickness of the muscle layers of the internal and external anal sphincter was assessed in the position of the intermediate dorsal anal canal in a randomized cross-over fashion. Study 2: In a study of similar design, sonography was performed in nine healthy volunteers by two investigators independently using a single ultrasound machine in three standardized positions (proximal/intermediate/distal anal canal) and the sphincter layers assessed in the left, right, and dorsal segment. RESULTS: Study 1: Both the same investigator with different ultrasound scanners and different investigators with the same machine failed to obtain reproducible results with respect to internal and external anal sphincter muscle layer diameter (four bivariate correlations, all with p > 0.05). Study 2: Standardization of the probe position did not improve the agreement (2 x 9 bivariate correlations, all but two p > 0.05). CONCLUSION: At present, therefore, endoanal ultrasound does not provide reliable morphometric data on anal sphincter muscle diameter. This could explain previously conflicting observations of associations between anal sphincter morphometry and function.

Comparison of anal sonography with conventional needle electromyography in the evaluation of anal sphincter defects.

OBJECTIVE: A comparison of anal sonography with conventional electromyographic mapping in the evaluation of anal sphincter defects was the aim of this study. METHODS: In 23 patients with defecatory problems referred for conventional needle electromyography (EMG), anal endosonography, with a 7.5-MHz, 355 degrees scanner, was performed before EMG to determine the structural integrity of the external anal sphincter. If lesions were found, they were described in terms of location and extent. Subsequently, concentric needle EMG of the external sphincter was performed circumferentially to locate muscle parts exhibiting normal and diminished or missing muscle activity. Lesions found by EMG were also described like those found by sonography. RESULTS: Of 23 patients, eight exhibited no abnormalities on EMG, and no muscle defects were identified endosonographically in any of these patients. In the remaining 15 patients, EMG showed either an incomplete pattern of interference or a complete absence of voluntary activity; in all of these patients endosonography also identified structural deficit. In 14 of these 15 patients, abnormalities were found at the same location with both endosonography and EMG. In the remaining patient, the two techniques identified structural and functional abnormalities at different locations. CONCLUSION: Although EMG is the gold standard for assessment of the functional relevance of muscle defects, anal endosonography yields a sensitivity and specificity of almost 100%.

Endosonography of the anal sphincters: incontinent and continent patients and healthy controls.

It has previously been shown that in healthy subjects anal sphincter functions as assessed by anorectal manometry and anal sphincter anatomy as measured by endoluminal ultrasound are poorly correlated. It remains to be shown, however, whether this is true for a larger series of patients with anorectal dysfunctions such as incontinence, and what is the clinical relevance of anal sonography. Anal sonography was performed in 42 consecutive patients with fecal incontinence, in 19 patients with constipation and/or anal pain, and in 15 healthy volunteers to determine anal sphincter integrity and the dorsal diameter of the internal and external anal sphincter muscles. Conventional multilumen anorectal manometry was performed in all subjects and patients to determine, among others, external and internal sphincter (EAS, IAS) performance at rest and during squeezing. It was shown that healthy subjects exhibit significantly higher muscle diameters of the IAS than both patient groups, but the EAS was similar in all groups. In 11/42 cases of incontinent patients, in 3/19 constipated patients, but in none of the controls a muscle defect of the EAS was found with sonography. Thirteen of these 14 patients were women with previous birth traumas. EAS but not IAS muscle thickness and muscle performance (squeezing and resting, respectively) were significantly correlated. Across all groups, women had smaller EAS muscle diameters than men. It is concluded, that in incontinent patients anal sonography may reveal additional information of clinical relevance in a substantial fraction of patients, and, thus, both anal manometry and anal ultrasound are of clinical value.

Sonographic, manometric, and myographic evaluation of the anal sphincters morphology and function.

PURPOSE: A direct comparison of anal sphincter physiology (muscle performance and anatomy-muscle thickness) has not yet been undertaken but may be of importance in patients with defecation disorders. METHODS: We evaluated 15 healthy volunteers by means of anorectal manometry to determine pressure functions of the internal and external and sphincter. Transcutaneous electromyography was recorded to assess the electrical activity of the external anal sphincter. Thickness of the anal sphincter muscles was measured sonographically from within the anal canal with dorsal projection using a 7.5-MHz 360 degrees rectal panorama scanner. RESULTS: It was shown that neither is the muscle thickness of the external anal sphincter during rest (6.26 +/- 1.02 mm) or during squeezing (7.40 +/- 1.39 mm) correlated to its squeeze pressure (138.8 +/- 15.2 mmHg), nor is the diameter of the internal anal sphincter (2.09 +/- 0.58 mm) correlated to its resting pressure (61.1 +/- 15.2 mmHg). Finally, the thicker the internal and sphincter muscle, the lower the electrical activity of the external anal sphincter during squeezing (r = 0.74, P < 0.001). CONCLUSION: It is concluded that both manometry to assess sphincter function and sonography to determine sphincter morphology are important measures in the evaluation of continence function.