An analysis of program and family costs of case managed care for technology-dependent infants with bronchopulmonary dysplasia

Influenza caused low levels of mortality and morbidity in England and Wales in the 1997/98 season. Influenza viruses of the H3N2 and H1N1 subtypes were isolated in small numbers from community and hospital patients in November and December. Their numbers subsequently increased to peak in February, H1N1 a week or two before H3N2. Most of the H1N1 isolates were similar to the A/Bayern/7/95-like virus, included in the vaccine recommended for 1997-98, whereas most H3N2 isolates were A/Sydney/5/97-like, a virus not covered by the season's vaccine but recommended for 1998/99. Consultation rates in general practice for influenza-like illnesses remained low until early February, when a small increase coincided with the increase in laboratory confirmed influenza. Fewer deaths directly attributed to influenza were registered during the surveillance period than in recent years. Localised outbreaks occurred in schools and nursing homes towards the end of the winter.     

A new class of tobacco chitinases homologous to bacterial exo-chitinases displays antifungal activity

A novel chitinase gene of tobacco was isolated and characterized by DNA sequence analysis of a genomic clone and a cDNA clone. Comparative sequence analysis of both clones showed an identity of 94%. The proteins encoded by these sequences do not correspond to any of the previously characterized plant chitinases of classes I-IV and are designated as class V chitinases. Comparison of the chitinase class V peptide sequence with sequences in the Swiss Protein databank revealed significant sequence similarity with bacterial exo-chitinases from Bacillus circulans, Serratia marcescens and Streptomyces plicatus. It was demonstrated that class V chitinase gene expression is induced after treatment of tobacco with different forms of stress, like TMV-infection, ethylene treatment, wounding or ultraviolet irradiation. Two related chitinase class V proteins of 41 and 43 kDa were purified from Samsun NN tobacco leaves inoculated with tobacco mosaic virus. The proteins were purified by Chelating Superose chromatography and gel filtration. In vitro assays demonstrated that class V chitinases have endo-chitinase activity and exhibit antifungal activity toward Trichoderma viride and Alternaria radicina. In addition, it was shown that class V chitinase acts synergistically with tobacco class I beta-1,3-glucanase against Fusarium solani germlings.     

NMDA receptors mediate peripheral chemoreceptor afferent input in the conscious rat

N-methyl-D-aspartate (NMDA) glutamate receptors mediate critical components of cardiorespiratory control in anesthetized animals. The role of NMDA receptors in the ventilatory responses to peripheral and central chemoreceptor stimulation was investigated in conscious, freely behaving rats. Minute ventilation (VE) responses to 10% O2, 5% CO2, and increasing intravenous doses of sodium cyanide were measured in intact rats before and after intravenous administration of the NMDA receptor antagonist MK-801 (3 mg/kg). After MK-801, eupcapnic tidal volume (VT) decreased while frequency increased, resulting in a modest reduction in VE. Inspiratory time (TI) decreased, whereas expiratory time remained unchanged. The VE responses to hypercapnia were qualitatively similar in control and MK-801 conditions, with slight reductions in respiratory drive (VT/TI) after MK-801. In contrast, responses to hypoxia were markedly attenuated after MK-801 and were primarily due to reduced frequency changes, whereas VT was unaffected. Sodium cyanide doses associated with significant VE increases were 5 and 50 microg/kg before and after MK-801, respectively. Thus 1-log shift to the right of individual dose-response curves occurred with MK-801. Selective carotid body denervation reduced VE during hypoxia by 70%, and residual hypoxic ventilatory responses were abolished after MK-801. These findings suggest that, in conscious rats, carotid and other peripheral chemoreceptor-mediated hypoxic ventilatory responses are critically dependent on NMDA receptor activation and that NMDA receptor mechanisms are only modestly involved during hypercapnia.     

Structural and functional analogy between pneumolysin and proaerolysin

Pneumolysin and proaerolysin are bacterial toxins that form pores in host cells by oligomerization. We propose that they may have similar structures despite a poor sequence identity. The crystal structure of proaerolysin reveals a protein composed of four domains, arranged in the shape of an elongated comma. Electron microscopy of the pneumolysin monomer shows a similar arrangement of domains. The sequence of pneumolysin recognizes the template of proaerolysin from a library of protein folds. A three-dimensional model of pneumolysin has been constructed by the comparative approach using the structure of proaerolysin. This model, together with results on the activity of site- specific mutants and the positions of antigenic sites, has been used to propose functional roles of individual domains.      

Apoptosis and its role in human disease

In a landmark paper published over two decades ago, Kerr et al. proposed the term apoptosis "for a hitherto little recognized mechanism of controlled cell deletion, which appears to play a complementary but opposite role to mitosis in the regulation of animal cell populations". In the ensuing years, this natural cell death process was studied at the basic science level, primarily with a view to understanding its roles in cancer and in the development and maintenance of the immune system. More recently, however, evidence has suggested a role for the failure of normal apoptosis control in many of the major diseases of the industrialized world. Though complex, apoptosis appears amenable to therapeutic intervention. The range of modern pharmaceutical strategies available to treat such disregulated gene-directed processes offers promise for advances in the control of cancer, immune system and neurodegenerative disorders, heart disease, and perhaps even the aging process itself.     

Fractures of the first rib in child abuse

PURPOSE: To evaluate the incidence and specificity of fracture of the first rib as an indicator of child abuse and to determine a mechanism of fracture. MATERIALS AND METHODS: All infants and young children with rib fractures who were seen at the radiology department of an academic medical center over a 2-year period were identified from the radiology data base. RESULTS: Rib fractures were attributed to child abuse in 12 of 35 children identified. Apart from a neonate with congenital osteogenesis imperfecta, only three children, all abused, had first-rib fracture, one bilaterally. Two additional children with first-rib fracture were identified from years prior to the study period. In four children, first-rib fractures were "isolated," without fractures of adjacent bones. CONCLUSION: Child abuse should be considered in cases of pediatric rib fracture, particularly fracture of the first rib. Possible mechanisms for first-rib fracture include impact force, compressive force, and shaking or acute axial load (slamming), which cause an indirect fracture.     

The crystal structure of a 3D domain-swapped dimer of RNase A at a 2.1-A resolution

The dimer of bovine pancreatic ribonuclease A (RNase A) discovered by Crestfield, Stein, and Moore in 1962 has been crystallized and its structure determined and refined to a 2.1-A resolution. The dimer is 3D domain-swapped. The N-terminal helix (residues 1-15) of each subunit is swapped into the major domain (residues 23-124) of the other subunit. The dimer of bull seminal ribonuclease (BS-RNase) is also known to be domain-swapped, but the relationship of the subunits within the two dimers is strikingly different. In the RNase A dimer, the 3-stranded beta sheets of the two subunits are hydrogen-bonded at their edges to form a continuous 6-stranded sheet across the dimer interface; in the BS-RNase dimer, it is instead the two helices that abut. Whereas the BS-RNase dimer has 2-fold molecular symmetry, the two subunits of the RNase A dimer are related by a rotation of approximately 160 degrees. Taken together, these structures show that intersubunit adhesion comes mainly from the swapped helical domain binding to the other subunit in the "closed interface" but that the overall architecture of the domain-swapped oligomer depends on the interactions in the second type of interface, the "open interface." The RNase A dimer crystals take up the dye Congo Red, but the structure of a Congo Red-stained crystal reveals no bound dye molecule. Dimer formation is inhibited by excess amounts of the swapped helical domain. The possible implications for amyloid formation are discussed.     

Effects of a startling acoustic stimulus on reaction time in different parkinsonian syndromes

BACKGROUND: The functional assessment of the startle circuit is usually done by analyzing the acoustic startle response (ASR). However, a startling acoustic stimulus (SAS) also induces changes in the excitability of neural structures that can be demonstrated by studying the SAS-induced change in the behavior of certain neurophysiologic responses. OBJECTIVE: To examine the effects induced by an SAS on voluntary reaction time in patients with parkinsonian syndromes (StartReact effect) and to compare the results with those obtained in a group of age-matched healthy volunteers. METHODS: Twelve patients with idiopathic PD (IPD), seven patients with progressive supranuclear palsy (PSP), seven patients with multisystem atrophy (MSA), and seven healthy age-matched control volunteers performed a simple visual reaction time task and received SAS together with the "go" signal in random trials. RESULTS: Baseline reaction time was significantly slower in PSP patients than in control subjects and MSA patients. The SAS induced a significant shortening of the reaction time in control subjects and in patients with IPD and MSA, but not in patients with PSP. The percentage of reaction time shortening with regard to the baseline values also differed significantly between PSP patients and the other groups of subjects. The StartReact effect was consistent throughout the experiment and showed reduced habituation with repeated testing. CONCLUSIONS: The results are consistent with an abnormal function of the startle circuit in patients with PSP and agree with previous studies using the ASR. The reduced habituation of the StartReact effect favors its clinical applicability in the assessment of differences between patients with parkinsonian syndromes.     

Treating achalasia: from whalebone to laparoscope

Reports of bile duct injuries are from tertiary care institutions and, therefore, may not report the spectrum of management that these patients receive in the care of these injuries. From June 14,1990 (the first operation) to June 30, 1995, 2654 laparoscopic cholecystectomies (LCs) were reviewed at this community hospital medical center to determine risk factors contributing to the etiology of these injuries, time and symptoms at presentation, duration of illness, and management of these injuries. None of the 13 general surgeons practicing during this time period had laparoscopic training in a general surgical residency. There were six major bile duct injuries (0.25%), of which five were available for further review. All occurred in women with cholelithiasis and chronic cholecystitis. Two operations were routine and two were associated with biliary tract anomalies. In two patients, the injuries were detected at LCs and definitive biliary-enteric anastomoses were performed immediately. Three patients presented at 2, 15, and 42 days after LC. In two patients, one or more operative procedures were performed before definitive repair and these patients were referred to tertiary care centers. One patient was managed with sequential CT-guided drainage catheters after attempted closure of the defect. The length of illness for these five patients was 8, 69, 348, 402, and 435 days with a follow-up of 245, 345, 531, 575, and 1088 days. Laparoscopic experience before injury by the operating surgeon was 3, 26, 35, 77, and 333 operations. Major biliary tract injuries occurred during routine cholecystectomy, length of illness was substantial for most patients, and biliary-enteric anastomosis was definitive for four of the five patients. The operating surgeons' "learning curve" did not seem as important as in other studies.