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1. Salmonella Gallinarum strains isolated from a southern Brazil fowl typhoid outbreak were subjected to phenotypic and genotypic analyses to identify genetic elements that could improve prevention and control strategies. 2. Whole-genome sequencing revealed the presence of the aac(6')-Iaa gene, conferring aminoglycoside resistance, along with novel chromosomal point mutations, including the first detection of parE p.S451F in Salmonella Gallinarum. 3. Additionally, IncFII(S) plasmid replicons, Salmonella pathogenicity islands and 105 virulence genes associated with cell adhesion, invasion and antimicrobial peptide resistance were identified. 4. These findings shed light on the molecular mechanisms of fowl typhoid and provide crucial insights into emerging antimicrobial resistance and virulence factors. [ABSTRACT FROM AUTHOR]

1. Salmonella Gallinarum (SG) infections cause fowl typhoid, which leads to important economic losses. Multidrug resistance (MDR) and the capacity for bacteria to form biofilms could play an important role in the persistence of SG in poultry flocks resulting in intermittent disease outbreaks. The aim of the following study was to assess the lytic activity of two new bacteriophages (Salmonella phages UPF_BP1 and UPF_BP2) against MDR and biofilm-forming SG. 2. Forty-six strains of SG, isolated in 2015, were characterised by antimicrobial resistance, biofilm formation profiles and susceptibility to two new bacteriophages. 3. Of these strains, 24% were multidrug resistant and more than 80% formed biofilm, with no statistical difference between incubation temperatures (42°C or 22°C). With regard to the lytic activity of the phages, 85% of strains were susceptible to at least one phage. Of these, 74% were lysed by both phages, including MDR and biofilm producing strains. 4. The use of salmonella phages UPF_BP1 and UPF_BP2 were shown to be promising alternatives for the biological control of fowl typhoid. [ABSTRACT FROM AUTHOR]

An outbreak of conjunctivitis caused by adenovirus type 4 (AV 4) occurred in hospital personnel who had contact with a patient with AV 4 pneumonia. Nine ill individuals were identified. AV 4 infection was demonstrated in all by isolation of AV 4 and/or a fourfold or greater rise in serum titer of specific neutralizing antibody. The incubation period was seven to 10 days, and the illness lasted five to seven days. Infectious virus was regularly present in the affected eyes for one week but not usually for more than 10 days after the onset of symptoms. Visual disturbance persisted for at least five months in one patient, who developed subepithelial deposits. The outbreak occurred after isolation procedures were abandoned in the care of the patient. No secondary case appeared. Isolation of patients with adenovirus pneumonia and barrier nursing are recommended as practical means of preventing nosocomial adenoviral infection and its consequences. [ABSTRACT FROM PUBLISHER]

Objective: To quantify the protective efficacy of influenza vaccine in elderly persons.Data Sources: A MEDLINE search was done using the index terms influenza vaccine, vaccine efficacy, elderly, mortality, hospitalized, and pneumonia. Appropriate references in the initially selected articles were also reviewed.Study Selection: Only cohort observational studies with mortality assessment were included in the meta-analysis. In addition, 3 recent case-control studies, 2 cost-effectiveness studies, and 1 randomized, double-blind, placebo-controlled trial were reviewed.Data Extraction: Vaccine and epidemic virus strains, age and sex of patients, severity of illness, patient status, and study design were recorded. Upper respiratory illness, hospitalization, pneumonia, and mortality were used as outcome measures.Data Synthesis: In a meta-analysis of 20 cohort studies, the pooled estimates of vaccine efficacy (1-odds ratio) were 56% (95% Cl, 39% to 68%) for preventing respiratory illness, 53% (Cl, 35% to 66%) for preventing pneumonia, 50% (Cl, 28% to 65%) for preventing hospitalization, and 68% (Cl, 56% to 76%) for preventing death. Vaccine efficacy in the case-control studies ranged from 32% to 45% for preventing hospitalization for pneumonia, from 31% to 65% for preventing hospital deaths from pneumonia and influenza, from 43% to 50% for preventing hospital deaths from all respiratory conditions, and from 27% to 30% for preventing deaths from all causes. The randomized, double-blind, placebo-controlled trial showed a 50% or greater reduction in influenza-related illness. Recent cost-effectiveness studies confirm the efficacy of influenza vaccine in reducing influenza-related morbidity and mortality and show that vaccine provides important cost savings per year per vaccinated person.Conclusion: Despite the paucity of randomized trials, many studies confirm that influenza vaccine reduces the risks for pneumonia, hospitalization, and death in elderly persons during an influenza epidemic if the vaccine strain is identical or similar to the epidemic strain. Influenza immunization is an indispensable part of the care of persons 65 years of age and older. Annual vaccine administration requires the attention of all physicians and public health organizations. [ABSTRACT FROM AUTHOR]

Choledochal cyst or biliary tract cyst is a pathological condition characterized by abnormal dilation of the hepatobiliary system. In veterinary medicine, case descriptions and histological characterizations of this biliary malformation are scarce, requiring reliance on data from human medicine. A presumptive diagnosis typically involves imaging studies, with histopathological examination required for confirmation. Treatment often involves surgical intervention to remove the cyst and restore normal biliary function. A 15-year-old mixed-breed domestic female cat presented with vomiting and anorexia. Ultrasonographic examination revealed a dilation adjacent to the caudal aspect of the gallbladder. The patient underwent surgical intervention, during which a sacculation in the cystic duct region was identified and completely excised. Histopathological analysis confirmed the diagnostic suspicion of a biliary tract cyst. Despite the limited veterinary literature, the success of the surgical intervention, involving complete cyst removal, was evident. The patient remains stable and fully recovered twelve months post-surgery., Competing Interests: Declarations. Ethical approval: The work described in this manuscript involved the use of a non-experimental (owned) animal. High, internationally recognized standards (“best practices”) of veterinary clinical care for patients were always followed. Consent to participate: Informed consent was obtained from the owner or legal custodian of the animal described in this work for all procedures undertaken. No animals or people are identifiable within this publication, and therefore additional informed consent for publication was not required. Competing interests: The authors declare no competing interests., (© 2025. The Author(s), under exclusive licence to Springer Nature B.V.)

Opioid abuse is a healthcare and societal problem that burdens individuals, their families and the healthcare professionals who care for them. Restricting access to opioid analgesics is one option to deter abuse, but this may prevent pain patients in need from obtaining effective analgesics. Therefore, strategies that mitigate the risk of opioid abuse while maintaining access are being pursued by several stakeholders including federal agencies, state governments, payors, researchers, the pharmaceutical industry and clinicians. Federal agency efforts have included required licensure and documentation for prescribing opioids, implementation of risk evaluation and mitigation strategies, and guidance on assessment and labeling of opioid abuse-deterrent formulations. In addition, state governments and payors have enacted monitoring programs, and pharmaceutical companies continue to develop abuse-deterrent opioid formulations. Strategies for clinicians to mitigate opioid abuse include comprehensive patient assessment and universal precautions (e.g. use of multimodal analgesia and abuse-deterrent opioid formulations, urine toxicology screening, participation in prescription drug monitoring and risk evaluation and mitigation strategy programs).

Background: For midlife and older women, this period of their life is associated with an increase in risk factors for the development of chronic medical conditions. Data confirms the importance of regular exercise for both prevention and management of cardiovascular and other non-communicable diseases, unwanted weight gain, worsening metabolic profile and osteoporosis. However, in most clinical practices, midlife and older women patients are not offered specific exercise guidance., Objectives: This review assessed the current environment of what exercise advice is being offered to women at clinical encounters and suggests ways of incorporating an exercise prescription into clinical practice., Materials and Methods: A PubMed review of the literature from the past 20 years was conducted., Results: A universal template for an exercise prescription for aging women does not exist. Globally, there are scant programs that offer exercise advice and interventions to patients at the end of clinical encounters., Conclusions: Although most aging women know the benefits of engaging in a regular exercise program, many do not establish a regular routine. By the clinician offering an exercise prescription, this not only reinforces the importance of exercise but also provides simple guidelines on how women can commence an exercise routine in their life., (Copyright © 2015. Published by Elsevier Ireland Ltd.)

• For almost 60 years, the WHO Global Influenza Surveillance and Response System (GISRS) has been the key player in monitoring the evolution and spread of influenza viruses and recommending the strains to be used in human influenza vaccines. The GISRS has also worked to continually monitor and assess the risk posed by potential pandemic viruses and to guide appropriate public health responses. • The expanded and enhanced role of the GISRS following the adoption of the International Health Regulations (2005), recognition of the continuing threat posed by avian H5N1 and the aftermath of the 2009 H1N1 pandemic provide an opportune time to critically review the process by which influenza vaccine viruses are selected. In addition to identifying potential areas for improvement, such a review will also help to promote greater appreciation by the wider influenza and policy-making community of the complexity of influenza vaccine virus selection. • The selection process is highly coordinated and involves continual year-round integration of virological data and epidemiological information by National Influenza Centres (NICs), thorough antigenic and genetic characterization of viruses by WHO Collaborating Centres (WHOCCs) as part of selecting suitable candidate vaccine viruses, and the preparation of suitable reassortants and corresponding reagents for vaccine standardization by WHO Essential Regulatory Laboratories (ERLs). • Ensuring the optimal effectiveness of vaccines has been assisted in recent years by advances in molecular diagnosis and the availability of more extensive genetic sequence data. However, there remain a number of challenging constraints including variations in the assays used, the possibility of complications resulting from non-antigenic changes, the limited availability of suitable vaccine viruses and the requirement for recommendations to be made up to a year in advance of the peak of influenza season because of production constraints. • Effective collaboration and coordination between human and animal influenza networks is increasingly recognized as an essential requirement for the improved integration of data on animal and human viruses, the identification of unusual influenza A viruses infecting human, the evaluation of pandemic risk and the selection of candidate viruses for pandemic vaccines. • Training workshops, assessments and donations have led to significant increases in trained laboratory personnel and equipment with resulting expansion in both geographical surveillance coverage and in the capacities of NICs and other laboratories. This has resulted in a significant increase in the volume of information reported to WHO on the spread, intensity and impact of influenza. In addition, initiatives such as the WHO Shipment Fund Project have facilitated the timely sharing of clinical specimens and virus isolates and contributed to a more comprehensive understanding of the global distribution and temporal circulation of different viruses. It will be important to sustain and build upon the gains made in these and other areas. • Although the haemagglutination inhibition (HAI) assay is likely to remain the assay of choice for the antigenic characterization of viruses in the foreseeable future, alternative assays - for example based upon advanced recombinant DNA and protein technologies - may be more adaptable to automation. Other technologies such as microtitre neuraminidase inhibition assays may also have significant implications for both vaccine virus selection and vaccine development. • Microneutralization assays provide an important adjunct to the HAI assay in virus antigenic characterization. Improvements in the use and potential automation of such assays should facilitate large-scale serological studies, while other advanced techniques such as epitope mapping should allow for a more accurate assessment of the quality of a protective immune response and aid the development of additional criteria for measuring immunity. • Standardized seroepidemiological surveys to assess the impact of influenza in a population could help to establish well-characterized banks of age-stratified representative sera as a national, regional and global resource, while providing direct evidence of the specific benefits of vaccination. • Advances in high-throughput genetic sequencing coupled with advanced bioinformatics tools, together with more X-ray crystallographic data, should accelerate understanding of the genetic and phenotypic changes that underlie virus evolution and more specifically help to predict the influence of amino acid changes on virus antigenicity. • Complex mathematical modelling techniques are increasingly being used to gain insights into the evolution and epidemiology of influenza viruses. However, their value in predicting the timing and nature of future antigenic and genetic changes is likely to be limited at present. The application of simpler non-mechanistic statistical algorithms, such as those already used as the basis of antigenic cartography, and phylogenetic modelling are more likely to be useful in facilitating vaccine virus selection and in aiding assessment of the pandemic potential of avian and other animal influenza viruses. • The adoption of alternative vaccine technologies - such as live-attenuated, quadrivalent or non-HA-based vaccines - has significant implications for vaccine virus selection, as well as for vaccine regulatory and manufacturing processes. Recent collaboration between the GISRS and vaccine manufacturers has resulted in the increased availability of egg isolates and high-growth reassortants for vaccine production, the development of qualified cell cultures and the investigation of alternative methods of vaccine potency testing. WHO will continue to support these and other efforts to increase the reliability and timeliness of the global influenza vaccine supply. • The WHO GISRS and its partners are continually working to identify improvements, harness new technologies and strengthen and sustain collaboration. WHO will continue in its central role of coordinating worldwide expertise to meet the increasing public health need for influenza vaccines and will support efforts to improve the vaccine virus selection process, including through the convening of periodic international consultations., (© 2011 Blackwell Publishing Ltd.)

Although influenza virus infection of humans has been associated with a wide spectrum of clinical neurological syndromes, the pathogenesis of influenza virus associated central nervous system (CNS) disease in humans remains controversial. To better study influenza virus neuropathogenesis, an animal model of influenza-associated CNS disease using human virus isolates without adaptation to an animal host was developed. This neonatal rat model of influenza virus CNS infection was developed using low-passage human isolates and shows outcomes in specific brain regions, cell types infected, and neuropathological outcomes that parallel the available literature on cases of human CNS infection. The degree of virus replication and spread in the rat brain correlated with the strains' neurotoxicity potential for humans. In addition, using sensitive neurobehavioral test paradigms, changes in brain function were found to be associated with areas of virus replication in neurons. These data suggest that further evaluation of this pathogenesis model may provide important information regarding influenza virus neuropathogenesis, and that this model may have possible utility as a preclinical assay for evaluating the neurological safety of new live attenuated influenza virus vaccine strains.

The yield of influenza virus in eggs is critical to influenza vaccine production and availability, but the contribution of specific genes to the growth properties of influenza B viruses is not well understood. Influenza B/Beijing/184/93 and B/Shangdong/7/97 were chosen for study because B/Shangdong/7/97 replicated to several fold higher titers in eggs than B/Beijing/184/93 as demonstrated by hemagglutination titers and EID50. A reassortant with the HA, NP and PB2 genes from B/Beijing/184/93 and all other genes from B/Shangdong/7/97 had the high growth phenotype of B/Shangdong/7/97 in eggs, which suggests that NS, M, NA, PB1 or PA, or a combination of these genes derived from B/Shangdong/7/97 were needed for the high growth phenotype of the reassortants. A high degree of homology was found among the genetic sequences of B/Beijing/184/93, B/Shangdong/7/97, and other influenza B viruses. However, differences potentially related to growth characteristics were suggested by analysis of the deduced amino acid (AA) sequences of four genes: NS (NS1, NS2), M (BM2), NA (NA, NB) and PB1. The studies identify multiple genes that may affect growth of influenza B viruses in eggs.

Influenza vaccines are unique because they require a licensing process which includes a procedure for rapid annual updates to vaccine strains. The licensing procedures in the European Union and the USA are described as examples. In the event of an influenza pandemic, vaccines will be required urgently and licensing process should reflect such needs.

Because of delays in the manufacturing of the 2000-2001, trivalent inactivated influenza vaccine in the US, there were concerns that there might be shortages of vaccine supply in the US. Therefore, we conducted a prospective, randomized, open-label, multicenter trial at six academic medical centers in the US, to evaluate the immunogenicity of a half dose of inactivated vaccine in healthy adults. Healthy adults between the ages of 18 and 49 were randomized to receive either a full 0.5ml (15.5 microg of each HA antigen) dose or a 0.25ml (7.75 microg of each HA antigen) dose of the 2000-2001 trivalent inactivated influenza vaccine by intramuscular injection. Sera were obtained for assessment of hemagglutination-inhibiting antibody to each of the three strains contained in the vaccine before and 21 days after vaccination. The proportions of individuals achieving a post-vaccination titer of > or =1:40, the geometric mean titers (GMTs) of post-vaccination antibody, and the proportions of individuals with a four-fold or greater increase in antibody were lower for all three strains in those receiving 0.25ml of vaccine compared to those receiving 0.5ml. However, the differences were small for all three antigens. The upper 95% confidence limits for differences between 0.25 and 0.5ml doses were less than 20% for rates of achieving a titer of > or =1:40 and four-fold response, and less than 1.5 for the ratios of GMTs between dose groups, for all three vaccine antigens. These results suggest that when vaccine is in short supply, a strategy using a half dose in healthy adults could increase the number of people vaccinated with relatively little adverse impact on vaccine immunogenicity.

The formation of influenza virus ribonucleoprotein (RNP) is a necessary step in viral assembly and maturation in infected cells, but the mechanism remains incompletely understood. Influenza virus proteins such as matrix (M1) and cellular proteins have been implicated in assembly and transport of RNP. To study the assembly of RNP and the translocation of RNP complexes in cells, RNPs were reconstituted from nucleoprotein (NP), M1, and viral RNA (vRNA) synthesized in vitro. The syntheses were accomplished using specific plasmids in a system coupling transcription and translation under the control of the T7 promoter. The density of the resulting RNP complexes was analyzed by glycerol gradient centrifugation and the morphology was examined by transmission electron microscopy. Protomers of NP self-assembled into circular oligomers regardless of the presence of vRNA or M1. However, helical structures similar in conformation and density to RNPs purified directly from influenza virus were formed only when M1 and vRNA were also present. In the absence of vRNA, no helical structures were formed from NP and M1. The plasmids also contained the CMV promoter, which permitted expression of M1, NP, and vRNA in Madin-Darby canine kidney (MDCK). M1 and NP were both present in the cytoplasm of MDCK also expressing vRNA, but NP was retained in the nucleus of cells expressing M1 without vRNA. Our data demonstrate for the first time that vRNA and M1 together promote the self-assembly of influenza virus NP into the quaternary helical structure typical of the viral RNP. The results also indicate that the interaction of NP with vRNA and M1 in a system devoid of other viral proteins can lead to translocation of RNP from nucleus to cytoplasm.

To characterize the sites and nature of binding of influenza A virus matrix protein (M1) to ribonucleoprotein (RNP), M1 of A/WSN/33 was altered by deletion or site-directed mutagenesis, expressed in vitro, and allowed to attach to RNP under a variety of conditions. Approximately 70% of the wild-type (Wt) M1 bound to RNP at pH 7.0, but less than 5% of M1 associated with RNP at pH 5.0. Increasing the concentration of NaCl reduced M1 binding, but even at a high salt concentration (0.6 M NaCl), approximately 20% of the input M1 was capable of binding to RNP. Mutations altering potential M1 RNA-binding regions (basic amino acids 101RKLKR105 and the zinc finger motif at amino acids 148 to 162) had varied effect: mutations of amino acids 101 to 105 reduced RNP binding compared to the Wt M1, but mutations of zinc finger motif did not. Treatment of RNP with RNase reduced M1 binding by approximately half, but even M1 mutants lacking RNA-binding regions had residual binding to RNase-treated RNP provided that the N-terminal 76 amino acids of M1 (containing two hydrophobic domains) were intact. Addition of detergent to the reaction mixture further reduced binding related to the N-terminal 76 amino acids and showed the greatest effect for mutations affecting the RNA-binding regions of basic amino acids. The data suggest that M1 interacts with both the RNA and protein components of RNP in assembly and disassembly of influenza A viruses.

The United States Code of Federal Regulations requires that all influenza virus vaccines produced for use in the United States adhere to specific regulatory standards including the demonstration of safety and efficacy. For vaccines produced in cell lines, rigorous characterization for manufacturing is particularly important. Influenza vaccines produced by the passage of viruses in mammalian cell lines will require careful evaluation to ensure the removal or inactivation of potential adventitious agents.

Objective: To determine the effect of repeated annual influenza immunization on the host's serum antibody., Design: Ten year observational study with cohort design., Setting: Cystic Fibrosis Center at St. Vincent's Hospital and Medical Center, New York City, NY., Patients: Thirty-eight children and young adults with cystic fibrosis (CF)., Measurements: Serum hemagglutination inhibition (HI) antibody titers were determined at the time of vaccination and 4 weeks later each year in the fall before the influenza epidemic. Shwachman scores were determined each year., Results: While the pre-vaccination and post-vaccination geometric mean serum HI antibody titers varied from year to year, no upward or downward trend was evident over the 10 year period. The reciprocal of the post-vaccination geometric mean HI titers ranged annually from 32 to 74 for the influenza A (H3N2) vaccine strains, from 53 to 133 for the influenza A (H1N1) strains, and from 18 to 174 for influenza B strains. In addition, the majority of vaccinees had a presumably protective post-vaccination serum HI titer > or = 1:40 each year for all three vaccine strains. The initial mean Shwachman score of the group was 77. The final score of 76 after 10 years was not significantly different., Conclusions: Annual influenza vaccination appears to regularly induce presumably protective serum antibody levels in most CF children and young adults studied over a 10 year period.

The time to the appearance of a peak serum antibody response to influenza virus vaccine is not clearly defined. We compared the most commonly used time intervals described in the literature--4 and 6 weeks after vaccination. We studied 118 elderly patients from three different geographic sites. The 1992 to 1993 trivalent inactivated influenza virus vaccine containing influenza virus A/Beijing/353/89 (H3N2), influenza virus A/Texas/36/91 (H1N1), and influenza virus B/Panama/45/90 was used. No statistically significant differences were found at the 4- and 6-week intervals after vaccination.

The purpose of this study was to determine whether acetaminophen impairs the immune response to influenza vaccine. Influenza vaccine is an under-utilized preventive measure, partly because of the unfounded perception that fever and myalgias frequently follow vaccination. While acetaminophen may decrease these infrequent side effects, it may also alter the immune response to vaccination. We compare the effect of acetaminophen with placebo on the humoral immune response to the 1991-1992 commercially available influenza vaccine. We studied 60 healthy, elderly subjects from a geriatric clinic and 20 infirm, elderly subjects from a nursing home. The subjects were randomly assigned to receive placebo or acetaminophen (1,000 mg every 6 h) for 2 days. Acetaminophen did not depress or enhance the immune development of serum hemagglutination inhibition antibody to the three vaccine antigens. The systemic side effects of fever and myalgia were uncommon in both groups. The healthy elderly subjects mounted a significantly better immune response to the influenza virus A/Taiwan/1/86 (H1N1) vaccine strain than did the infirm elderly subjects (geometric mean titer, 115 versus 51; P = 0.003). The functional activity score obtained by using the chronic healthy evaluation component of the Acute Physiology and Chronic Health Evaluation system could be used to distinguish the healthy from the infirm elderly (scores of 1.27 versus 3.75, P < 0.001). Acetaminophen neither depressed nor enhanced the serum antibody response to the vaccine in the healthy and infirm elderly subjects studied.

The cocirculation in several parts of the world of influenza viruses B/Yamagata/16/88 and B/Victoria/2/87, which are genetically and antigenically divergent, has prompted the question of whether immunization with one viral antigen is sufficient for protection against both strains. Twenty-three high-risk infants and young children were immunized with a commercial trivalent influenza vaccine containing the antigens of influenza virus B/Yamagata/16/88. When antibodies against influenza viruses B/Yamagata/16/88 and B/Victoria/2/87 were determined, increases developed uniformly to both in the sera of primed children previously exposed to influenza virus B/Victoria/2/87 by immunization or infection. Antibodies against B/Yamagata/16/88 developed in the sera of unprimed children with titers similar to those of the primed children. However, antibodies to B/Victoria/2/87 were not detected in the sera of the unprimed children. These data suggest that children without appropriate immunologic priming may not be protected against an infection with a B/Victoria/2/87 strain after vaccination with a B/Yamagata/16/88 strain. Immunization with more than one influenza B virus strain may be desirable in some high-risk pediatric patients if divergent influenza B viruses circulate.

Natural killer-like cellular cytotoxicity was augmented by incubation of human rhinovirus serotype 2 with peripheral blood mononuclear leukocytes collected from healthy donors. The production of alpha interferon but not gamma interferon was identified in the same cell cultures. A specific interaction of conformationally intact rhinovirus with peripheral blood mononuclear leukocytes was required for induction of the response, since the response was extinguished at reduced quantities of infectious rhinovirus, and acid inactivated rhinovirus did not augment cellular cytotoxicity. Productive replication of rhinovirus was not observed in cultures of peripheral blood mononuclear leukocytes. The replicative failure was not related merely to interferon production, since the rate of disappearance of rhinovirus was similar to that observed in cell free medium. The findings suggest that natural killer cells should be considered as a potential component of the local nasopharyngeal pathophysiology of rhinovirus infection.

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Disseminated cytomegalovirus (CMV) infection in a liver transplant recipient was treated successfully by administration of ganciclovir (BW B759U) at a dosage of 7.5 mg/kg/day for 2 wk in the face of continuation of chemical immunosuppression. The spectrum of illness included symptomatic esophagitis and hepatic dysfunction associated with the appearance of CMV inclusion bodies, retinal lesions, and bone marrow suppression. Clinical improvement during therapy with ganciclovir was prompt and was paralleled by reversal of histological abnormalities. CMV was recovered from none of the cultured tissues after the start of therapy. Ten months after discontinuation of ganciclovir, the patient had no evidence of further CMV disease. The observation suggests that replicative CMV infection in organ-transplanted patients may be suppressed by relatively low dose ganciclovir, even when the patients are maintained on immunosuppressive regimens designed to prevent graft rejection.

Necrotizing external otitis is a slowly progressive infection of the ear canal and basal skull caused by Pseudomonas aeruginosa. Treatment with aminoglycoside and antipseudomonal penicillin antibiotics significantly reduces extension of infection, decreases the severity of the associated cranial nerve injury, and limits disease-related mortality. Combined antimicrobial and surgical treatment appears to be more efficacious than antibiotics alone when evaluated for comparable stages of the disease. However, invasive surgical procedures may promote the spread of infection, particularly in the absence of appropriate antibiotic therapy. A high index of suspicion for the syndrome should be aroused when external otitis is present for longer than two weeks, especially after local debridement and topical antibiotic treatment. Aggressive use of systemic antibiotic therapy in diabetic patients, who are at greatest risk, should reduce disease extension and lessen the need for multiple surgical procedures.

Populations of peripheral blood leukocytes were enumerated in 15 volunteers challenged by intranasal inoculation with rhinovirus serotype 25. The results demonstrated a significant decrease in total lymphocyte count among infected persons on the third day after challenge with the virus (P less than .01). The change in lymphocyte count was associated with a significant decrease in total T cells, as determined by monoclonal antibodies (both T11+ and T3+, P less than .02), but not in B cells (B7+). Among the subsets of T cells, T4+ (T helper/inducer) and T8+ (T suppressor/cytotoxic) lymphocytes both declined in number, but only the change in the T4+ subset was significant. For each of the lymphocyte populations that decreased significantly (T3+, T11+, and T4+) there was a strong correlation with increased severity of symptoms. Persons who had the greatest decrease in total lymphocyte count also shed virus most frequently. The number of nonlymphocyte leukocytes increased with the severity of the symptoms. These data show that T lymphocytes (particularly the T4+ population) are related to both the progression of infection and the symptoms of the rhinovirus common cold.

Leukocyte populations in the secretions of volunteers challenged by intranasal inoculation with rhinovirus serotype 25 were evaluated by means of flow cytometry. With the light-scatter properties of peripheral blood leukocytes as the standard of reference, significant increases (P less than .05) of both lymphocytes and phagocytes (polymorphonuclear leukocytes plus monocytes) were detected in the nasal secretions of persons infected by the viral challenge. There was a direct correlation of nasopharyngeal symptom severity with both the percentage of lymphocytes (P less than .05) and the percentage of phagocytes (P less than .001). Monoclonal antibodies for specific cell-membrane antigens identified the lymphocytes and phagocytes as leukocytes and also demonstrated the presence of a population of monocytic cells during the phase of maximal symptoms. The panel of monoclonals chosen did not unequivocally identify a lymphocyte population except in the presence of nosebleed. However, the results show that flow cytometry can be used to investigate nasal-secretion cell populations during the rhinovirus common cold.

Four volunteers with naturally acquired, culture-proved influenza A infection inhaled a radiolabeled aerosol to permit investigation of lung mucociliary clearance mechanisms during and after symptomatic illness. Mucus transport in the trachea was undetectable when monitored with an external multidetector probe within 48 hours of the onset of the illness, but was found at a normal velocity (4.9 +/- 1.9 mm/min) by 1 week in three of the four subjects. In two volunteers who coughed 23 to 48 times during the 4.5-hour observation period, whole lung clearance was as fast within the first 48 hours of illness as during health 3 months later in spite of the absence of measurable tracheal mucus transport. Conversely, in spite of the return 1 week later of mucus transport at velocities expected in the trachea, whole lung clearance for the 4.5-hour period was slowed in two volunteers who coughed less than once an hour. The data offer evidence that cough is important in maintaining lung clearance for at least several days after symptomatic influenza A infection when other mechanisms that depend on ciliary function are severely deficient.