Study of the mass transfer kinetics in a monolithic column.

The purpose of this work is to investigate the mass transfer kinetics of butylbenzoate on a monolithic RPLC column, with methanol-water (65:35, v/v) as the mobile phase. We used the perturbation method, measuring the height equivalent to a theoretical plate (HETP) of the peaks obtained as the response to small pulses of solute injected on a concentration plateau. The equilibrium isotherm of butylbenzoate was previously determined by frontal analysis. It is well accounted for by a liquid-solid extended multilayer BET isotherm model. The equilibrium data derived from the pulse method are in excellent agreement with those of frontal analysis in the accessible concentration range of 0 to 8 g/dm3. Plots of the HETP of small pulses. injected on eight different plateau concentrations, were acquired in a wide range of mobile phase flow velocities. The axial dispersion and the mass transfer kinetic coefficients were derived from these data. The validity of these measurements is discussed. The mass kinetics of butylbenzoate depends strongly on the plateau concentration. Processes involving adsorptive interactions between the solute and the stationary phase, e.g. surface diffusion and adsorption-desorption kinetics, combine in series to the external mass transfer kinetics and to effective pore diffusivity.

Comparison of the adsorption equilibrium of a few low-molecular mass compounds on a monolithic and a packed column in reversed-phase liquid chromatography.

Adsorption isotherm data were acquired by frontal analysis for several low-molecular mass compounds (3-phenyl 1-propanol, 4-tert.-butylphenol, butylbenzene, and butyl benzoate) on a classical packed column and a monolithic column using methanol-water RP-HPLC conditions. These columns have similar characteristics (C18-bonded silica, close specific surface areas and bonding densities). In each case, the isotherm model best accounting for the data was the same on both columns. The solute polarity determines the class of this model. For the two -OH compounds it was a Langmuirian adsorption isotherm. The hydrocarbon data were best modeled by an anti-Langmuir convex-downward isotherm model. The adsorption data for the aromatic ester exhibited a nearly linear behavior, depending on the methanol concentration of the mobile phase. A slightly convex downward isotherm was obtained at high methanol concentrations while the best fitting was obtained with a liquid-solid extended multilayer B.E.T. isotherm model at low concentrations. The validation of these models is discussed in detail. In all cases, similar values of the adsorption-desorption constants were found, underlining the closeness of the adsorption energies on both columns. By contrast, the adsorption capacity of the monolithic column was found to be approximately 1.4 greater than that of the packed column in spite of the close values of the surface areas of the silica in both columns.

Invasive Aspergillosis in Italian AIDS patients.

BACKGROUND: We studied the prevalence, epidemiological features, symptoms, diagnosis, treatment and outcome of invasive aspergillosis in AIDS patients in Italy. PATIENTS AND METHODS: All patients affected by both aspergillosis and AIDS hospitalized between January 1986 and April 1997 (before highly-active antiretroviral therapy, HAART) in four Italian Department of Infectious Disease. Patients were included in the study only if culture, cytology or histology showed firm evidence of Aspergillus infection. Invasive aspergillosis was defined as the presence of characteristic, closely septate hyphae with repeated acute angle branching in either biopsy materials or percutaneous aspirates from tissues other than the lung. Hyphae were identified using hematoxylin-eosin and methenamine silver stain. RESULTS: During the study, 54 out of 2,614 patients admitted with AIDS showed aspergillosis (2.1%). The disease usually occurred in patients with < 50 CD4 cells/mm(3). Aspergillosis was associated with neutropenia and steroid treatment. Nonspecific symptoms were frequently encountered. Fever and cough were both present in > 70% of the cases of pulmonary aspergillosis. Biopsy specimens were analyzed for definitive diagnosis. Invasive aspergillosis is usually treated with amphotericin B, but in 90% of the cases this did not prevent death. CONCLUSION: In AIDS patients with neutropenia and long-term steroid therapy, it is important to consider invasive aspergillosis in the differential diagnosis of opportunistic infections.

Low frequency of severe hepatotoxicity and association with HCV coinfection in HIV-positive patients treated with HAART.

BACKGROUND: Highly active antiretroviral therapy (HAART) is strongly effective in reducing morbidity and mortality in HIV-1-positive individuals. Its main drawback is the potential toxicity. Data on the frequency and determinants of severe hepatotoxicity in a clinical setting are still sparse. METHODS: This is a prospective study of HIV-1-positive individuals with known HBsAg and HCV-Ab serology. The study end point was progression to alanine aminotransferase (ALT) levels > or =200 IU/L after HAART initiation. Cumulative probability of progression to this end point was estimated by the Kaplan-Meier method. Crude and adjusted hazard ratios (HR) were estimated by proportional hazards regression model. RESULTS: One thousand two hundred fifty-five patients were included. HBsAg was found in 91 (7.2%), HCV-Ab in 578 (46.5%) patients; almost all injection drug users (451 of 482; 93.6%) were HCV-Ab positive. Sixty-one individuals progressed to the end point with a probability of 7.9% (95% confidence interval [CI], 5.6-10.0) of progression at 24 months from starting. Independent factors predicting progression to the end point were baseline ALT levels (HR, 5.29; 95% CI, 3.24-8.65; every 10 IU/L higher), HCV-Ab positivity (HR, 4.01; 95% CI, 1.48-10.85) or both HBsAg and HCV Ab positivity (HR, 3.85, 95% CI, 1.01-14.61), and previous non-HAART therapy (HR, 1.84, 95% CI, 1.04-3.42). Patients receiving stavudine-containing regimens had a lower risk than those receiving zidovudine-containing regimens (HR, 0.30, 95% CI, 0.12-0.71). CONCLUSIONS: There was a low risk of ALT > or =200 IU/L in our cohort. Hepatitis C coinfection and elevated ALT levels at HAART initiation are important predictors of progression to ALT > or =200 IU/L; stavudine-containing regimens were associated with a lower risk compared with zidovudine-containing regimens.

Liquid crystalline polymers as stationary phases. IV. Chemical bonding and immobilization of the polymer on silica characterization by solid-state nuclear magnetic resonance spectroscopy.

Chemical bonding reaction and immobilization through low energy radiation (heating) have been investigated to fix a side-chain liquid crystalline polymer (SC-LCP) on silica particles in order to use the resulting modified silica in normal-phase HPLC. Highly stable chromatographic stationary phases are observed under excellent polymer solvent flow conditions (THF) for both methods and better column efficiencies are also exhibited towards PAHs' separation compared to the classical coated stationary phase. The characterization of these new stationary phases and the rationale for improved column stability have been investigated by solid state 13C and 29Si CP/MAS NMR spectroscopy. It is clearly shown that the chemical bonding is achieved by the classical hydrosilylation reaction between PHMS chains and vinyl modified silica. The bonded polymer is likely a copolymer than a homopolymer. The immobilization of the SC-LCP by heating results in the breaking of Si-O-Si bonds of the polysiloxane chain after the attack of the silica surface silanols. Applications to fullerenes and carotenes separation of these bonded stationary phases are compared to the separation power of a classical monomeric C18 stationary phase in NP-HPLC as n-hexane-toluene or methyl-tertiobutyl ether-methanol mixtures.

Laterally attached liquid crystalline polymers as stationary phases in reversed-phase high-performance liquid chromatography. V. Study of retention mechanism using linear solvation energy relationships.

A linear solvation energy relationship model was used to characterize the retention behavior of a stationary phase based upon a nematic side-on liquid crystalline polymer (SOLCP) in reversed-phase liquid chromatography. The set of solutes was constituted of a high variety of compounds whose molecular sizes were considerably smaller than the mesogenic unit size. The results showed good statistical fits for these retention data in 65:35, 75:25 and 85:15 (v/v) methanol-water mobile phases. Both the cavity term and excess molar refraction are the most important favorable retention-governing parameters, whereas the solute hydrogen bond acceptor basicity is the most unfavorable retention parameter. Hydrophobicity and pi-pi interactions decrease strongly when the percentage of methanol increases, leading to an important retention decrease despite the fact that the hydrogen bond interaction weakens as the organic solvent is added. The shape recognition ability of this side-on liquid crystalline stationary phase on polycyclic aromatic hydrocarbon solutes is partly explained by the solutes' high polarizability due to the presence of pi-electrons. However, the solute polarizability is not sufficient and a stationary phase's "structure effect" must to be taken into account for the shape discrimination observed. The strong interaction between liquid crystal molecules caused likely a adsorption retention mechanism rather than a partition mechanism.

Laterally attached liquid-crystalline polymers as stationary phases in reversed-phase high-performance liquid chromatography. III. Effect of the local anisotropic order on the separation of polycyclic aromatic hydrocarbons.

Specific stationary phases based upon non-liquid-crystalline polymers, liquid-crystalline molecules and side-on fixed liquid-crystalline polymers (SO-LCP) have been synthesized for use as silica modified stationary phases in high-performance liquid chromatography (HPLC). The mesogenic side group of the SO-LCP was composed of three phenyl ring benzoate type with terminal alkoxy chains and was laterally linked to a polysiloxane backbone via an alkyl ester spacer arm. This study demonstrated that the shape recognition of stationary phases based upon SO-LCP towards the length-to-breath ratio (L/B) was strongly connected to the existence of a local liquid-crystalline order into the pores of silica gel, warranting the interest of the collective organization of mesomorphic materials in liquid chromatography. Furthermore, the chromatographic performances depended on the kind of anisotropic order and it was more advantageous to use smectic side-on liquid-crystalline polymer than nematic and obviously non-liquid-crystalline ones. Finally, for a series of polymers having the same mesomorphism, the larger the temperature stability range of the mesophase, the more pronounced the local order effect and the higher the shape recognition.

Laterally attached liquid crystalline polymers as stationary phases in reversed-phase high-performance liquid chromatography. II. Optimization of the molecular parameter of the polymer.

Stationary phases obtained by coating side-chain liquid crystalline polymers (LCPs) with the mesogenic rod like units laterally attached to a polysiloxane backbone via a flexible spacer have been already reported. These phases show excellent planarity and shape recognition for polynuclear aromatic hydrocarbon (PAH) solutes in reversed-phase liquid chromatography. Optimization of these stationary phases in terms of molecular parameters of the polymer is here described. Fifteen stationary phases have been prepared varying different parameters such as the spacer length, the aliphatic tail length, and the proportion of laterally attached mesogenic units along the polymer chain. The results show that the combination of a long spacer and long terminal chains, which generates a smectic phase in the polymer bulk, leads to the best chromatographic performances towards planarity and shape recognition for PAH solutes.

Investigation of the nematic-isotropic transition of a liquid crystalline polymer and determination of molecular diffusion coefficients using gas chromatography.

Inverse gas chromatography has been used to study the nematic-isotropic transition of a side chain liquid crystalline polymer (LCP). The mesogenic side groups are laterally attached to a polysiloxane backbone through a flexible spacer. The nematic-isotropic transition of this LCP coated onto a glass capillary column is detected by considering the variation with temperature of the retention volume and of the theoretical plate number for the several probes. The molecular diffusion coefficients, D, of naphthalene, fluorene, pyrene and o-terphenyl have been determined at different temperatures in the nematic phase of the LCP as well as in the isotropic melt. The values ranged between 10(-14) and 10(-12) m2 s(-1) for the polynuclear aromatic hydrocarbon probes tested.

[Esophageal radiology in the patient with dysphagia: review in 333 patients]. / Radiología esofágica en el paciente con disfagia: revisión en 333 pacientes.

The authors presents a retrospective analysis from the results of radiologic examinations in patients with dysphagia in a private clinic. They were 333 patients studied with conventional and digital radiology, using conventional technic to perform the examines. The special technique (barium/crushing-ice) was used to provoke the possible motility disorders. The results were normal in 105 patients (31.5%) and pathologic in 228 patients (68.5%).

Insights into the reasons for discontinuation of the first highly active antiretroviral therapy (HAART) regimen in a cohort of antiretroviral naïve patients. I.CO.N.A. Study Group. Italian Cohort of Antiretroviral-Naïve Patients.

OBJECTIVE: To evaluate the frequency of discontinuation of the first highly active antiretroviral regimen (HAART) and the factors predictive of discontinuing for toxicity and failure in a population-based cohort of HIV-positive individuals in Italy, naïve from antiretrovirals at enrolment. METHODS: The study population consisted of individuals who initiated HAART and had at least one follow-up visit. The primary end-points were discontinuation of any component of HAART for drug toxicity and discontinuation for failure. Survival analyses were performed to identify predictive factors for reaching the two end-points. RESULTS: Eight hundred and sixty-two individuals initiated HAART; in 727 of them (84.3%) this consisted of two nucleoside reverse transcriptase inhibitors (NRTI) and one protease inhibitor (PI). Over a median follow-up of 45 weeks, 312 patients (36.2%) discontinued therapy: 182 (21.1%) discontinued due to toxicity, 44 (5.1%) due to failure. The probability of discontinuing HAART at 1 year was 25.5% [95% confidence interval (CI), 21.9-28.9] due to toxicity and 7.6% (95% CI, 4.9-1 0.3) due to failure. Independent factors associated with discontinuation for toxicity were: gender [relative hazard (RH) = 0.51; 95% CI, 0.32-0.80 for men versus women], type of treatment (indinavir-containing regimens, RH = 1.94; 95% CI, 1.10-3.41 and ritonavir-containing regimens, RH = 3.83; 95% CI, 2.09-7.03 versus hard-gell saquinavir) and time spent on treatment (RH = 0.89; 95% CI, 0.80-0.98 for each additional month). Discontinuation due to failure was independently associated with the most recent HIV-RNA (RH = 3.20; 95% CI, 1.74-5.88 for log10 copies/ml higher), and with type of treatment (indinavir-containing regimens, RH = 0.21; 95% CI, 0.06-0.78 and ritonavir-containing regimens, RH = 0.23; 95% CI, 0.04-1.26 versus hard-gell saquinavir). CONCLUSIONS: If the current HAART regimen caused no toxicity, less than 10% of naïve patients discontinue their first HAART regimen because of failure after 1 year from starting therapy.

Radiología esofágica en el paciente con disfagia: revisión en 33 pacientes / Esophageal radiology in the patient with dysphagia: review in 333 patients

OBJETIVOS: los autores presentan una revisión retrospectiva de los resultados de exámenes baritados efectuados a pacientes con diagnóstico clínico de disfagia, en una institución privada, comparando con los hallazgos de la literatura. MATERIAL Y MéTODO: se analizó el resultado en 333 pacientes estudiados con radiología convencional y digital, con técnica convencional de ingestión de bario o sustancia iodada y efectuando doble contraste con aire y con técnica especial (administración de hielo molido) para estudios de la motilidad. RESULTADOS: 105 pacientes (31,5 por ciento) presentaron un examen radiológico normal y 228 pacientes (68,5 por ciento) mostraron alteraciones: trastornos motores (31,2 por ciento), epitelio de Barret (4,5 por ciento), esofagitis (10,5 por ciento), compresiones extrínsecas (2,7 por ciento), divertículos (5,7 por ciento), cáncer avanzado (10,2 por ciento) y otros (3,7 por ciento).

Radiología esofágica en el paciente con disfagia: revisión en 333 pacientes. / [Esophageal radiology in the patient with dysphagia: review in 333 patients]

The authors presents a retrospective analysis from the results of radiologic examinations in patients with dysphagia in a private clinic. They were 333 patients studied with conventional and digital radiology, using conventional technic to perform the examines. The special technique (barium/crushing-ice) was used to provoke the possible motility disorders. The results were normal in 105 patients (31.5

) and pathologic in 228 patients (68.5

).

Radiología esofágica en el paciente con disfagia: revisión en 33 pacientes / Esophageal radiology in the patient with dysphagia: review in 333 patients

OBJETIVOS: los autores presentan una revisión retrospectiva de los resultados de exámenes baritados efectuados a pacientes con diagnóstico clínico de disfagia, en una institución privada, comparando con los hallazgos de la literatura. MATERIAL Y MéTODO: se analizó el resultado en 333 pacientes estudiados con radiología convencional y digital, con técnica convencional de ingestión de bario o sustancia iodada y efectuando doble contraste con aire y con técnica especial (administración de hielo molido) para estudios de la motilidad. RESULTADOS: 105 pacientes (31,5 por ciento) presentaron un examen radiológico normal y 228 pacientes (68,5 por ciento) mostraron alteraciones: trastornos motores (31,2 por ciento), epitelio de Barret (4,5 por ciento), esofagitis (10,5 por ciento), compresiones extrínsecas (2,7 por ciento), divertículos (5,7 por ciento), cáncer avanzado (10,2 por ciento) y otros (3,7 por ciento). (Au)

AZT plus methotrexate in HIV-related non-Hodgkin's lymphomas.

AZT is a thymidine analogue useful in the treatment of AIDS. It has been demonstrated that this compound can possess a significant antineoplastic activity when combined with de novo thymidylate synthesis inhibitors, such as 5-fluorouracil (5FU) and methotrexate (MTX). Here we report a review of our data concerning the efficacy and tolerance of the combination AZT + MTX in HIV-related non Hodgkin's lymphomas (NHL). Twenty-nine patients were treated, at weekly intervals, with three (patient 1 to 10) or six (patient 11 to 29) consecutive courses of MTX 1g/m2 and increasing doses of oral AZT (2, 4 and 6g/m2) with leucovorin rescue. Of 26 evaluable patients, a total (complete + partial) response rate of 77% was obtained. The median complete response duration was 16.8 months. There was one therapy-related death due to septic shock. Grade III-IV neutropenia was observed after 19% of the courses, but was prevented by G-CSF administration in 82/119 courses. Grade III-IV anemia was observed after 9% of the courses. In conclusion, the combination AZT + MTX was effective and well tolerated in our series of HIV-related NHL patients.

Cervicofacial and pulmonary actinomycosis associated with non-Hodgkin's lymphoma.

A case of cervicofacial and pulmonary actinomycosis associated with non-Hodgkin's lymphoma (NHL) is reported. The patient underwent antimicrobial treatment and surgical debridement of a palatine lesion. Complete clinical recovery was achieved. The presence of actinomycosis may obscure and delay the diagnosis of NHL.

A randomized trial (ISS 902) of didanosine versus zidovudine in previously untreated patients with mildly symptomatic human immunodeficiency virus infection.

In this multicenter study (ISS 902), 554 previously untreated patients with <500 CD4 cells/mm3 and mildly symptomatic human immunodeficiency virus disease were randomized to receive zidovudine or didanosine (ddI). After a mean follow-up of 20 months, 80 patients (40 zidovudine, 40 ddI) had died and 146 had at least one AIDS-defining event (73 zidovudine, 73 ddI). Overall, no difference was found between treatments with respect to progression to AIDS or death. The analysis of relative risk (RR) of progression over time, however, showed an initially minor risk for zidovudine patients and an inversion in the zidovudine-ddI RR in the second and third years of follow-up. Didanosine showed a greater effect on CD4 cell count response. The two drugs confirmed the toxicity patterns already reported in other trials, with a low occurrence of pancreatitis (ddI 1.3%, zidovudine 0.4%). The overall results suggest that, in this population, zidovudine and ddI monotherapies have comparable long-term clinical efficacy and that more powerful regimens should be preferred.

Italian multicentre study of didanosine compassionate use in advanced HIV infection. Italian BMS-906 Study Group.

The aim of the present study, a multicentre trial of didanosine (ddI) compassionate use, was to identify factors associated with a better outcome in patients given ddI monotherapy. Enrolled were 1047 HIV-positive patients intolerant of and/or unresponsive to zidovudine (ZDV) therapy, with CD4+ cell counts of < 200/microliter or AIDS. Didanosine was given at a dose of 250 mg b.i.d. (patients > or = 60 kg) or 167 mg b.i.d. (patients < 60 kg). Clinical examinations and laboratory tests were performed every two months. Endpoints included death, the occurrence of a new AIDS-defining disease, or permanent discontinuation of ddI for a severe adverse event. At entry, the median CD41 cell count was 47/microliter and the median duration of prior ZDV treatment 19 months; 446 patients (43%) were classified as having AIDS. Severe toxicity occurred in 143 subjects (14%); the frequency of pancreatitis was very low (0.2%). The benefit in terms of CD4+ cell counts was greater for patients whose counts exceeded 100/microliter at entry and remained at this level until month 12 in those patients still receiving treatment. Death and/or new AIDS-defining events were observed in 374 cases (36%) over a median follow-up of eight months. AIDS dementia was observed in 11 patients (1%). Multivariate analysis of survival without disease progression showed that the factors associated with a worse outcome include the severity of immunodepression, a diagnosis of AIDS at entry, and a history of both intolerance of and clinical resistance to ZDV. Surprisingly, the patients who had received previous prolonged treatment with ZDV had a better outcome. In conclusion, severely immunodepressed patients previously administered long-term monotherapy may receive a short-term benefit from being switched to another antiretroviral drug.

3'-Azido 3'-deoxythymidine + methotrexate as a novel antineoplastic combination in the treatment of human immunodeficiency virus-related non-Hodgkin's lymphomas.

We have previously reported that 3'-azido 3'-deoxythymidine (AZT) can possess a significant antineoplastic activity when combined with drugs that disrupt de novo thymidylate synthesis, such as 5-fluorouracil and methotrexate (MTX). The aim of the present study was to evaluate the efficacy and the tolerance of the combination AZT + MTX in human immunodeficiency virus (HIV)-related non-Hodgkin's lymphoma (NHL). Twenty-nine patients (22 men and 7 women), either newly diagnosed or pretreated, have been enrolled in the trial; the median age was 34 years, 45% had acquired immunodeficiency syndrome before lymphoma and 19 patients had less than 100 CD4 lymphocytes/microL. Histologic diagnoses were mainly Burkitt (27%) and diffuse large B-cell lymphoma (45%); extranodal involvement was present in 20 patients. The treatment plan included three weekly courses of MTX at 1 g/m2 (days 1, 8, and 15) plus oral AZT at 2 g/m2 (days 1, 2, and 3), 4 g/m2 (days 8, 9, and 10), and 6 g/m2 (days 15, 16, and 17), plus leucovorin rescue. From the eleventh patient on, in case of complete or partial remission, the treatment was continued with three additional courses, using AZT at the maximum dose. In 26 evaluable patients, the total (complete + partial) response rate was 77% (95% confidence interval, 58% to 89%), with complete remission (CR) in 46% of the patients (95% confidence interval, 29% to 65%). The median CR duration was 12.8 months. Grade III-IV neutropenia and anemia were observed in 52% and 31% of the courses, respectively. There was one therapy-related death due to bacteremia followed by septic shock; the only other recorded infection was a herpes vaginalis. In conclusion, we suggest that AZT + MTX is an effective and well-tolerated regimen in HIV-related NHL.

Preliminary observations using HIV-specific transfer factor in AIDS.

Twenty five HIV-1-infected patients, at various stages (CDC II, III and IV) were treated orally with HIV-1-specific transfer factor (TF) for periods varying from 60 to 1870 days. All patients were receiving antiviral treatments in association with TF. The number of lymphocytes, CD4 and CD8 subsets were followed and showed no statistically significant variations. In 11/25 patients the number of lymphocytes increased, whilst in 11/25 decreased; similarly an increase of the CD4 lymphocytes was observed in 11/25 patients and of the CD8 lymphocytes in 15/25. Clinical improvement or a stabilized clinical condition was noticed in 20/25 patients, whilst a deterioration was seen in 5/25. In 12/14 anergic patients, daily TF administration restored delayed type hypersensitivity to recall antigens within 60 days. These preliminary observations suggest that oral HIV-specific TF administration, in association with antiviral drugs, is well tolerated and seems beneficial to AIDS patients, thus warranting further investigation.