Alpha 1 anti-trypsin: one protein, many functions.

α-1 anti-trypsin (AAT) is the most abundant circulating serine protease inhibitor (serpin) and an acute phase reactant. Systemic deficiency in AAT (AATD) due to genetic mutations can result in liver failure and chronic lung disease such as emphysema. Considered the prototypic serpin, the emphysema observed in patients with AATD, consisting of progressive destruction of the alveoli and small airway structures, formed the basis of the protease/anti-protease imbalance theory of chronic obstructive pulmonary disease (COPD). Over the past decade, however, investigations of AATD have described multiple functions of AAT beyond those generally attributed to its antiprotease activity. Evidence now suggests that AAT plays an important role in modulating immunity, inflammation, proteostasis, apoptosis, and possibly cellular senescence programs. When integrated in vivo, these processes contribute to the lung maintenance program which preserves the lung despite a constant bombardment by damage associated molecular patterns (DAMPs) and/or pathogenassociated molecular patterns (PAMPs) initiated by cigarette smoke, pollutants, or infections. In this review, we discuss the clinical aspects of AATD as they pertain to emphysema; including similarities and differences to cigarette smoke-induced emphysema. Examining the lung maintenance program, we next consider the multiple mechanisms of airspace destruction and explore the role AATD contributes. Finally, we consider the data regarding treatment of AATD, including AAT supplementation and its current limitations, and suggest further avenues of research informed by the multiple functions of AAT.

Observation of eta' decays to pi+pi-pi0 and pi+pi-e+e-.

Using psi(2S)-->pi;{+}pi;{-}J/psi, J/psi-->gammaeta;{'} events acquired with the CLEO-c detector at the CESR e;{+}e;{-} collider, we make the first observations of the decays eta;{'}-->pi;{+}pi;{-}pi;{0} and eta;{'}-->pi;{+}pi;{-}e;{+}e;{-}, measuring absolute branching fractions (37_{-9};{+11}+/-4)x10;{-4} and (25_{-9};{+12}+/-5)x10;{-4}, respectively. For eta;{'}-->pi;{+}pi;{-}pi;{0}, this result probes the mechanism of isospin violation and the roles of pi;{0}/eta/eta;{'}-mixing and final state rescattering in strong decays. We also set upper limits on branching fractions for eta;{'} decays to pi;{+}pi;{-}micro;{+}micro;{-}, 2(pi;{+}pi;{-}), pi;{+}pi;{-}2pi;{0}, 2(pi;{+}pi;{-})pi;{0}, 3(pi;{+}pi;{-}), and invisible final states.

Observation of Upsilon(2S)-->etaUpsilon(1S) and search for related transitions.

We report the first observation of Upsilon(2S)-->etaUpsilon(1S), with a branching fraction B=(2.1(-0.6)+0.7(stat)+/-0.3(syst)) x 10(-4) and a statistical significance 5.3sigma. Data were acquired with the CLEO III detector at the CESR e+e(-) symmetric collider. This is the first process observed involving a b-quark spin flip. For related transitions, 90% confidence limits in units of 10(-4) are B(Upsilon(2S)-->pi0Upsilon(1S)) < 1.8, B(Upsilon(3S)-->etaUpsilon(1S)) < 1.8, B(Upsilon(3S)-->pi0Upsilon(1S)) < 0.7, and B(Upsilon(3S)-->pi0Upsilon(2S)) < 5.1.

The agricultural-industrial partnership for eliminating micronutrient malnutrition: the investment bargain of the decade.

The limitations of conventional approaches to eliminating micronutrient deficiencies drives the search for a sustainable paradigm. This manuscript argues that the public and private sectors must embark on modernization of the Asian food industry and reorientation of the international agricultural research complex so that nutritionally enriched essential foods will be affordable and accessible to the poor. It is recommended that this partnership take special care of the needs of Asian children. The costs of chronic undernutrition, availability of cost-effective strategies, and benefits of sustained nutrition improvement to individuals, families and nations are reviewed. The roles of food fortification, plant breeding and biotechnology, both actual and imminent, are described. The paper concludes that a recast Green Revolution directed to dietary quality may be the key to enhancing the learning and earning capacity of young Asians of the new millenium. No other technology offers as large an opportunity to improve lives...at such a low cost and in such a short time..." World Bank (1).

Social character of materialism.

Scores for 170 undergraduates on Richins and Dawson's Materialism scale were correlated with scores on Kassarjian's Social Preference Scale, designed to measure individuals' character structure. A correlation of .26 between materialism and other-directed social character suggested that an externally oriented reference system guides materialists' perceptions, judgments, acquisitions, and possessions.

Necrotizing pulmonary granulomata in a marijuana smoker.

We describe the case of a heavy marijuana and tobacco smoker who presented with progressive exertional dyspnea of 2 months' duration, and bilateral nodular lung infiltrates. Examination of the lung fields was normal, and lung function tests showed mild airflow obstruction with moderately reduced gas transfer. BAL returned green-black fluid consisting predominantly of macrophages laden with carbon pigment. Thoracoscopic lung biopsy showed miliary necrotizing granulomata with an alveolar exudate of carbon-laden macrophages within macroscopically blackened lung. The differential diagnosis of pulmonary granulomata in this patient is discussed.

The impact of foodborne calicivirus disease: the Minnesota experience.

The first outbreaks of Norwalk virus gastroenteritis in Minnesota were confirmed in 1982. Since then, Norwalk-like caliciviruses have been recognized to be the most common cause of foodborne disease outbreaks, accounting for 41% of all confirmed foodborne outbreaks in Minnesota from 1981-1998. Although laboratory confirmation of caliciviruses in stool samples was not attempted in most of these outbreaks, all conformed to epidemiologic criteria for defining outbreaks of Norwalk virus. Since 1996, the availability of polymerase chain reaction testing at the Minnesota Department of Health has allowed for the confirmation of calicivirus infection among patients involved in epidemiologically defined outbreaks of viral gastroenteritis. Results have confirmed the usefulness of characterizing foodborne disease outbreaks by epidemiologic criteria and also confirmed the importance of human caliciviruses as the leading cause of foodborne disease outbreaks in Minnesota.

The cardiac surgical patient's expectations and experiences of nursing care in the intensive care unit.

There is an abundance of research investigating patient satisfaction. However, few studies have addressed patient satisfaction by comparing patients' expectations of nursing care with the care they actually received. This qualitative study explores both cardiac surgical patients' preconceptions and expectations of nursing care in the intensive care unit (ICU) and their actual experience of nursing care while in the unit. Data were collected using a semistructured interview technique. Interviews took place prior to admission and following discharge from ICU, and were taped and transcribed. Using thematic analysis, major and minor themes emerged from the data. The preoperative interviews revealed that participants had clear expectations of the nurse's role in ICU. They expected the nurse who cared for them to be capable, intelligent, experienced and technically adept. Further, they wanted a nurse who would be vigilant and provide them with personalised care. Participants understood they would be vulnerable and looked to the nurse to help them through this period. Post-operative interviews revealed that when participants perceived vigilance or experienced personalised care from the nurses they felt reassured and secure. However, patients also described feelings of anxiety, apprehension, fear and other unexpected experiences, notably confusion and hallucinations. Recommendations suggest that modification to pre-operative patient education programs could lead to a reduction in anxiety in the post-operative period. They also highlight the importance, to the patients, of nurse caring activities. In addition, the findings suggest a need for staff education that addresses patient anxiety and post-operative psychological disturbances.

Pap smear screening at an urban aboriginal health service: report of a practice audit and an evaluation of recruitment strategies.

A culturally appropriate women's health service was established at an Aboriginal community-controlled health service in Darwin in 1994. An initial file audit found that 48% of included women had ever been screened with a Pap smear and 37% of women were considered to have been adequately screened. The enhancement of opportunistic screening by file tagging had a modest effect on screening coverage over a 12-month period for women who attended the health service. The proportion of these women who were adequately screened increased from 43% to 48% and of those ever screened increased from 54% to 62%. A randomised trial of recruitment interventions including personal approach, letter and control groups was subsequently performed for women for whom Pap smears were overdue or not recorded. The impact of both interventions on the number of Pap smears performed was low, with 7% of women in the personal approach group, 2% of women in the letter group and no women in the control group having Pap smears during the three-month follow-up period. Low rates of abnormalities were observed for women having Pap smears over a two-year period. The minimal effect of a formal reminder system and letters at this urban Aboriginal health service has resulted in a re-orientation of activities towards strengthening opportunistic screening and the continued promotion of Pap smears in a range of clinic and community settings. It is important to place Pap smear screening in the context of other social, economic and health priorities for Aboriginal women and health workers.

Clinical consultations in an aboriginal community-controlled health service: a comparison with general practice.

Clinical consultation at Danila Dilba, an Aboriginal community-controlled health service in Darwin, were compared with consultations in Australian general practice. We described 583 consultations, using a questionnaire based on the International Classification of Primary Care. The methods were similar to those of the Australian Morbidity and Treatment Survey (AMTS) of consultations in Australian general practice undertaken by the University of Sydney Family Medicine Research Unit. Compared with Australian general practice consultations, consultations with Danila Dilba were more complex: more young patients, more new patients, more home visits, more problems managed, more new problems and more consultations leading to emergency hospital admission. Skin infections, diabetes mellitus, chronic alcohol abuse, rheumatic heart disease (or rheumatic fever) and chronic suppurative otitis media were much more commonly managed at study consultations at Danila Dilba than at consultations with general practitioners in the AMTS. Nearly all patients saw an Aboriginal health worker first, and nearly half the consultations were with Aboriginal health workers alone. The results suggest possible limitations of fee-for-item Medicare funding of Aboriginal community-controlled health services compared with existing block grant funding.

Function of a rare variant of alpha-1-antitrypsin, phenotype P(i) EFranklin S, a poor inhibitor of human neutrophil elastase.

A 31-year-old woman with the rare alpha-1-antitrypsin (A1AT) phenotype P(i) EFranklin S presented to this laboratory. Since little is known about the EFranklin protein, a study was established to investigate the biochemical properties of this glycoprotein, notably its inhibitory activity against human neutrophil elastase (HNE), compared with that of the more common A1AT variants M and Z. The serum A1AT level of 1.8 g/l (reference range 0.8-2.2 g/l) and anti-neutrophil elastase capacity (ANEC) value of 28 microM (reference range 15-42 microM) of this variant were normal. However, the association rate constant (AC) of the isolated and purified EFranklin protein 2.7 (0.4) x 10(6) M-1 s-1 at 25 degrees C was significantly lower compared with that in the normal M variant 9.1 (0.9) x 10(6) M-1 s-1. This implies that this form of A1AT is expressed at normal levels in serum but is functionally impaired as an inhibitor of HNE. The in vivo serum inhibition time of HNE was estimated to be 66 ms for the purified EFranklin protein compared with 20 ms for the M protein. While this protein is not an efficient inhibitor of HNE, there are sufficient molecules in the serum to achieve 100% inhibition of HNE and to protect the lung against proteinase attack. In conclusion, individuals who inherit the rare EFranklin variant in conjunction with the M or S A1AT molecules do not appear to have a high risk for the development of emphysema.

Prospective evaluation of the utility of molecular techniques for diagnosing nosocomial transmission of multidrug-resistant tuberculosis.

OBJECTIVE: To compare molecular techniques with conventional diagnostic methods for evaluating nosocomial transmission of multidrug-resistant tuberculosis (MDR-TB). DESIGN: We conducted a 12-week postexposure inception cohort study of health-care personnel who had been exposed to a patient with MDR-TB. MATERIAL AND METHODS: In addition to baseline and follow-up tuberculin skin tests and chest roentgenography, weekly pulmonary specimens were evaluated by (1) auramine-rhodamine fluorescent staining, (2) culture for mycobacteria, and (3) polymerase chain reaction (PCR) to amplify IS6110, a nucleic acid insertion sequence unique to the Mycobactrium tuberculosis complex. RESULTS: The index patient's isolate of M. tuberculosis showed a mutation in codon 531 of the RNA polymerase beta subunit (rpoB) gene of M. tuberculosis, which is associated with rifampin resistance and considered a marker for this MDR-TB strain. All pulmonary and gastric specimens from study participants had negative auramine stains and cultures for mycobacteria, One person, however, had separate specimens with repeatedly positive PCR results for IS6110 sequences, but the specimens contained a wild-type M. tuberculosis rpoB codon 531 dissimilar from the index patient's strain. CONCLUSION: Although both molecular and conventional testing showed that no exposed person was infected with the MDR-TB strain, molecular test results were available sooner and seemed more sensitive for detecting M. tuberculosis in one exposed person, presumably in a preinfection or "colonized" stage. Molecular methods provided information that helped distinguish this person's M. tuberculosis strain from the index patient's MDR-TB strain. Additional prospective studies should assess the value of these molecular techniques in similar clinical settings.