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INT J TUBERC LUNG DIS 12(9):1102
2008 The Union
A randomised controlled trial of
2 Petty T I, Mitchell R S. Successful treatment of advanced
high-dose isoniazid adjuvant therapy for
i soniazid- and streptomycin-resistant pulmonary tuberculosis
with ethionamide, pyrazinamide, and isoniazid. Am Rev Respir Dis 1962; 86: 503–512.
The fi ndings by Katiyar et al. in a recent issue of the
3 Moulding T S. Should isoniazid be used in retreatment of tuber-
that the adjuvant use of high-dose isoniazid
culosis despite acquired isoniazid resistance? Am Rev Respir Dis 1981: 123: 262–264.
(INH) signifi cantly improves results when retreating
4 Canetti G, Kreis B, Thibier R, Gay P, Le Lirzin M. Current data on
multidrug-resistant tuberculosis (MDR-TB) is a wel-
primary resistance in pulmonary tuberculosis in adults in France.
come fi nding.1 An earlier non-randomized trial by
2nd survey of the Centre d’Etudes sur la Resistance Primaire:
Petty et. al. found similar superior results when high-
1965–1966. Rev Tuberc Pneumol (Paris) 1967; 31: 433–474.
dose isoniazid (INH) was added to a retreatment regi-
5 Morlock G P, Metchock B, Sikes D, Crawford J T, Cooksey R C.
A, and kat
G loci of ethionamide-resistant clinical My-
men of ethionamide (ETH) and pyrazinamide (PZA).2
isolates. Antimicrob Agents Chemother
In a discussion of this issue, I presented a line of rea-
soning that the superior results found by Petty et al. may have been specifi c for an ETH-containing regi-
men, as it is known that strains with INH resistance have an unusual pattern of cross-resistance with ETH.3
We thank Dr Moulding for his insightful comments on
Low-grade INH-resistant organisms are often resis-
the implications of our work.1 He raises an extremely
tant to ETH, and high-grade INH resistance organ-
pertinent question regarding the possibility of cross-
isms are more susceptible to ETH.4 Therefore, adding
resistance of isoniazid (INH) resistant strains with
high-dose INH kills the low-grade INH-resistant or-
prothionamide (PTH). All the subjects in our study
ganisms, leaving only high-grade INH-resistant organ-
received a standardized course of second-line anti-
isms that are more susceptible to ETH, resulting in
tuberculosis treatment that included PTH, and we do
better clinical results.3 Less compelling evidence was
not have laboratory data on the PTH resistance pro-
presented showing that there is a similar process of
fi le of these patients. The clinical protocol of our trial
cross-resistance between INH and PZA.3 Katiyar et
did not permit us to compare INH-resistant MDR-TB
al. added high-dose INH to regimens containing pro-
patients who did or did not receive PTH. Therefore, it
thionamide, kanamycin, levofl oxacin, cycloserine and
will not be possible to directly answer the question
PAS.1 Prothionamide and ETH are very similar in
raised from our study data. While generalizing the re-
structure, but it is unknown to me if they have the
sults of our trial one should therefore bear in mind that
same patterns of cross-resistance with INH.
the effectiveness of high-dose INH adjuvant therapy
The issue is important, because clinicians need to
was observed in the context of a PTH-containing regi-
know whether or not to add high-dose INH to all re-
men for second-line treatment. Generalization to other
treatment regimens or only to retreatment regimens
regimens will need more laboratory and clinical work.
containing specifi c drugs. A recent article by Morlock
Regarding reference 28 being misquoted, we would
et al., which described the genetic mechanism for the
like to clarify that the four references included to-
INH-ETH cross-resistance patterns, may prove to be
gether in our article were categorized as ‘other experi-
one line of investigation that could help answer this
ences’. We certainly could have been more explicit, but
what we wanted to convey was that INH has value in
Note: Reference #28 in the article by Kariyar et al.
both preventing and treating MDR-TB. We again
to one of my publications is apparently an error, since
thank Dr Moulding for these very helpful comments.
it addresses an entirely different issue.
Division of Respiratory and Critical Care
*Department of Tuberculosis &
Ganesh Shankar Vidyarthi Memorial
1 Katiyar S K, Bihari S, Prakash S, Mamtani M, Kulkarni H. A
† Lata Medical Research Foundation
randomised controlled trial of high-dose isoniazid adjuvant ther-apy for multidrug-resistant tuberculosis. Int J Tuberc Lung Dis
SON LAS INHALOCÁMARAS VALVULADAS UNA MEJOR OPCIÓN FRENTE A LOS ESPACIADORES A LA HORA DE FORMULAR INHALADORES DE DOSIS MEDIDA? Fabio Bolívar MD1, Elvira Aguilera MD2, Isabel C. Bolívar MD3 1. Departamento de Medicina Interna, Facultad de Salud, Universidad Industrial de Santander (UIS). Bucaramanga, Colombia. 2. Subgerente Mediplast Ltda. Bucaramanga, Colombia. 3. Comité Cie
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