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Ptr_654 121.123Pediatr Transplantation 2007: 11: 121–123.
Copyright Ó 2007 Blackwell Munksgaard A daring treatment and a successfuloutcome: The need for targeted therapies forpediatric respiratory viruses The report by Stankova et al. in this issue tells ribavirin was used to treat nine of 27 HPIV- the fascinating and inspiring story of a child with infected stem cell transplant patients, without SCID who underwent two sequential human eﬀect on mortality rate (18).
stem cell transplantations (HSCT), a myeloabla- In a small pilot study designed to address tive pre-conditioning regimen, and many post- preemptive therapy in HSCT patients, Chakrabar transplant complications, all while she was et al. treated ﬁve patients with HPIV3 infection – actively infected with human parainﬂuenza virus one asymptomatic and four symptomatic with type 3 (HPIV3). The child never developed severe URTI – with oral ribavirin. Three of these respiratory disease, and three yr later had no individuals, including the patient who had been evidence of damage to the respiratory tract. The asymptomatic at the initiation of therapy, had no child's physicians had elected to initiate aeroso- virologic response. One of those three died; the lized ribavirin two wk before HSCT, and con- other two (including the person with no symp- tinued this medication for 10 months in an eﬀort toms of respiratory disease) were placed on IV to prevent the HPIV3 infection from progressing ribavirin and resolved. The role of ribavirin in in severity; the report cautiously suggests that preventing progression of URTI is uncertain, at this therapy may have contributed to the grat- best. In the patient treated by Stankova et al., the ifying outcome.
question of the signiﬁcance of risk factors makes This brave physiciansÕ report begs the ques- interpretation even more diﬃcult. Known risks tion: Why are we relying on untested, unproven, for increased mortality from HPIV3 after trans- partially active agents for a virus that is so plantation include graft vs. host disease, steroid important in children? The valiant attempt to use, and the presence of copathogens (2, 11, 17); treat parainﬂuenza viral respiratory tract disease the child had none of these. However, infection with ribavirin points to our more general with HPIV3 within the ﬁrst 100 days after trans- dilemma for pediatric respiratory viral diseases; plant has also been associated with increased we are often guessing, trying therapies based mortality (2), and this patient was certainly upon thin evidence for their use for a diﬀerent infected throughout the high-impact period. This pathogen, or on inadequate in vitro data. Even combination of high and low risk factors makes it for RSV, ribavirin is a nucleoside analog that has even more diﬃcult to evaluate the role of ribavirin good activity against RSV in vitro but has in the positive outcome.
produced conﬂicting clinical data and uncer- The child in this case was treated for upper tainty with regard to its utility in most cases.
respiratory tract infection (URTI), in an eﬀort to As far as ribavirin use in cases of HPIV3 prevent progression to lower respiratory tract infection, most reports have focused on early disease (LRTI). LRTI is a well-known conse- diagnosis and treatment. The authors of this quence of URTI infection with HPIV3; in one piece seem to have been the ﬁrst to treat active study of 228 patients who underwent bone HPIV3 infection, in anticipation of transplant.
marrow transplantation and acquired HPIV3 Published reports do not suggest a strong link infection, 198 individuals presented with symp- between ribavirin use in cases of HPIV infection toms of URTI, and 24% of these progressed to and improved outcome. In one large series, LRTI (11). Although the authors of that study did not speciﬁcally comment on the role of The F-triggering process itself also may be a ribavirin in preventing progression of disease target for antiviral strategies. First, based upon an from URTI to LRTI, there was no diﬀerence in analysis of the F-triggering process, peptides the 30-day mortality for treated patients and corresponding to speciﬁc domains of the F protein untreated patients. The child in the Stankova can be designed to prevent the F protein from et al. case report did go on, in fact, to develop reaching its fusion-active state. This strategy is HPIV3 LRTI, from which she recovered.
proving to be eﬀective at improving the design of Why did the physicians in this case have no antiviral peptides for related viruses (13). Finally, speciﬁc, targeted, tested, and eﬀective agents at while we have shown that speciﬁc mutations in the their disposal? The pediatric respiratory viral stalk region of HN aﬀect HN's ability to trigger F pathogens – including the well-known RSV and protein (16), and that speciﬁc features of the the parainﬂuenza viruses – have lagged far globular head region of HN modulate this trig- behind inﬂuenza virus in terms of research gering function (12), we do not yet know how the focus and funding. For inﬂuenza, eﬀective signal for activation is transmitted from HN to F antiviral drugs have emerged from the scientiﬁc protein. An understanding of this pathway should advances of the last two decades. Antiviral lead to additional targets for interruption of entry development for RSV and parainﬂuenza has, in and new antiviral agents. These several potential comparison, been strikingly absent. Pediatric therapeutic targets are being actively pursued. It is respiratory diseases have received low levels of to be hoped that future dedicated physicians like funding compared with other ﬁelds of health Stankova et al. will not have to rely on a long shot research (7), and only limited resources have or a guess, but will have at the ready several been devoted to RSV or parainﬂuenza antiviral strategies to protect and treat children with drug development, despite the recognized im- parainﬂuenza virus infection.
pact of these diseases in children (6). And whileeﬀective strategies of prophylaxis for RSV are Patricia DeLaMora1 and Anne Moscona1,2 available to protect the groups at most risk (3), 1Departments of Pediatrics and 2Microbiology and there are no tools for the parainﬂuenza viruses.
Immunology, Weill Medical College of Cornell University Stankova et al. therefore had to go out on a New York, NY, USA limb, and they were lucky.
Several advances, based upon basic research, are ready to be applied to the prevention of acuterespiratory disease (6, 8). These strategies are worth pursuing, to develop targeted antiviral 1. Alymova IV, Portner A, Takimoto T, Boyd KL, Babu YS, compounds for parainﬂuenza virus. The parain- McCullers JA. The novel parainﬂuenza virus hemagglutinin- ﬂuenza viruses enter their target cell by binding neuraminidase inhibitor BCX 2798 prevents lethal synergism to a receptor molecule and then fusing their viral between a paramyxovirus and Streptococcus pneumoniae.
envelope with the cell membrane to access the Antimicrob Agents Chemother 2005: 49: 398–405.
cytoplasm. Binding is mediated by the viral 2. Elizaga J, Olavarria E, Apperley J, Goldman J, Ward K.
hemagglutinin-neuraminidase (HN), which then Parainﬂuenza virus 3 infection after stem cell transplant:Relevance to outcome of rapid diagnosis and ribavirin treat- activates an adjacent fusion protein (F) to ment. Clin Infect Dis 2001: 32: 413–418.
mediate viral fusion into the cell (8, 12, 16).
3. Groothuis J, Simoes E, Levin M, et al. Prophylactic admin- Both binding and fusion are critical steps, and istration of respiratory syncytial virus immune globulin to interfering at the entry stage of the viral life cycle high-risk infants and young children. N Engl J Med 1993: 329: could prevent disease. We identiﬁed and func- tionally characterized speciﬁc receptor-interact- 4. Huberman K, Peluso R, Moscona A. The hemagglutinin- neuraminidase of human parainﬂuenza virus type 3: Role of ing sites on the HPIV3 HN molecule (4, 9, 10), the neuraminidase in the viral life cycle. Virology 1995: 214: and once the 3-D crystal structure of the HN protein was solved (5), we mapped these func- 5. Lawrence MC, Borg NA, Streltsov VA, et al. Structure of tional sites onto the HN structure (14). Making the haemagglutinin-neuraminidase from human parainﬂuenza use of this information, binding inhibitors can virus type III. J Mol Biol 2004: 335: 1343–1357.
6. Loughlin GM, Moscona A. The cell biology of acute child- now be designed speciﬁcally to ﬁt into the hood respiratory disease: Therapeutic implications. Pediatr binding pocket on the globular head of HN (1, Clin North Am 2006: 53: 929–959.
15). In addition to interfering with receptor 7. Michaud CM, Murray CJ, Bloom BR. Burden of disease – binding by the HN protein, this blockade would implications for future research. JAMA 2001: 285: 535–539.
interfere with the F-triggering function of the 8. Moscona A. Entry of parainﬂuenza virus into cells as a target HN protein, which can only occur when the HN for interrupting childhood respiratory disease. J Clin Invest2005: 115: 1688–1698.
protein is in contact with its receptor.
9. Moscona A, Peluso RW, Relative aﬃnity of the human enza type 3 and Newcastle disease virus hemagglutinin-neura- parainﬂuenza virus 3 hemagglutinin-neuraminidase for sialic minidase receptor binding: Eﬀect of receptor avidity and steric acid correlates with virus-induced fusion activity. J Virol 1993a: hindrance at the inhibitor binding sites. J Virol 2004: 78: 67: 6463–6468.
10. Murrell M, Porotto M, Weber T, Greengard O, Moscona 15. Porotto M, Fornabaio M, Greengard O, Murrell MT, A. Mutations in human parainﬂuenza virus type 3 HN causing Kellogg GE, Moscona A. Paramyxovirus receptor-binding increased receptor binding activity and resistance to the molecules: Engagement of one site on the hemagglutinin- transition state sialic acid analog 4-GU-DANA (zanamivir).
neuraminidase protein modulates activity at the second site.
J Virol 2003: 77: 309–317.
J Virol 2006: 80: 1204–1213.
11. Nichols WG, Corey L, Gooley T, Davis C, Boeckh M.
16. Porotto M, Murrell M, Greengard O, Moscona A. Trig- Parainﬂuenza virus infections after hematopoietic stem cell gering of human parainﬂuenza virus 3 fusion protein(F) by the transplantation: Risk factors, response to antiviral therapy, hemagglutinin-neuraminidase (HN): An HN mutation dimin- and eﬀect on transplant outcome. Blood 2001: 98: 573–578.
ishing the rate of F activation and fusion. J Virol 2003: 77: 12. Porotto M, Murrell M, Greengard O, Doctor L, Mosc- ona A. Inﬂuence of the human parainﬂuenza virus 3 attach- 17. Sparrelid E, Ljungman P, Ekelof-Andstrom E, et al.
ment protein's neuraminidase activity on its capacity to Ribavirin therapy in bone marrow transplant recipients with activate the fusion protein. J Virol 2005: 79: 2383–2392.
viral respiratory tract infections. Bone Marrow Transplant 13. Porotto M, Doctor L, Carta P, et al. Inhibition of Hendra 1997: 19: 905–908.
virus membrane fusion. J Virol 2006: 80: 9837–9849.
18. Wendt C, Weisdorf D, Jordan M, Balfour H, Hertz M.
14. Porotto M, Murrell M, Greengard O, Lawrence M, Parainﬂuenza virus respiratory infection after bone marrow McKimm-Breschkin J, Moscona A. Inhibition of parainﬂu- transplantation. N Engl J Med 1992: 326: 921–926.
Physician substance abuse and addiction: recognition, intervention, and recovery by Michael Kaufmann, MD OMA Physician Health Program The OMA Physician Health Program (PHP) was founded in 1995, with an initial mandate to provide assistance to physicians who experience problems with drug and alcohol abuse and addiction. Since its inception, the program has