Mutation Lys758 --> Ile of the sarcoplasmic reticulum Ca2+-ATPase enhances dephosphorylation of E2P and inhibits the E2 to E1Ca2 transition

The highly conserved lysine residue Lys758 in the fifth stalk segment of the sarcoplasmic reticulum Ca2+-ATPase was substituted with either isoleucine or arginine by site-directed mutagenesis. The substitution with arginine was without significant effects on Ca2+-ATPase function, whereas multiple changes of functional characteristics were observed with the Lys758 --> Ile mutant. These included insensitivity of ATPase activity to the calcium ionophore A23187, an alkaline shift of the pH dependence of ATPase activity, reduced maximum molecular turnover rate and steady-state phosphorylation level, reduced apparent affinities for Ca2+ and inorganic phosphate, as well as increased sensitivity to inhibition by vanadate. Analysis of the partial reaction steps of the enzyme cycle traced these changes to two steps. The rate of dephosphorylation of the ADP-insensitive phosphoenzyme intermediate (E2P) was increased, irrespective of variations of pH, K+, Ca2+, and dimethyl sulfoxide concentration. In addition, the rate of conversion of the dephosphoenzyme with low Ca2+ affinity (E2) to the Ca2+-bound form activated for phosphorylation (E1Ca2) was reduced in the mutant, and the ATP-induced rate enhancement of this step required higher ATP concentrations in the mutant compared with the wild type.     

Management of flatback and related kyphotic decompensation syndromes

STUDY DESIGN: The authors, in this retrospective study, examined a group of patients with flatback syndrome and a related kyphotic decompensation syndrome. Results of nonrealignment treatment as well as revision surgery with sagittal realignment were reviewed. OBJECTIVES: To determine effectiveness of physical therapy and limited surgical (instrumentation removal) as well as major realignment surgical treatment in the sagittally malaligned spine. SUMMARY OF BACKGROUND DATA: Flatback is a sagittal plane deformity associated with distraction instrumentation for scoliosis correction. Kyphotic decompensation syndrome involves malaligned fusions from the sacrum for disease other than scoliosis. Several studies describe surgical realignment for flatback involving instrumentation systems no longer commonly applied. Guidelines for a systematic approach to flatback and kyphotic decompensation syndromes are lacking. METHODS: Forty-eight patients with flatback and kyphotic decompensation syndromes were reviewed. Treatment groups were defined by treatment approach and level of previous fusion. Effectiveness of treatment was reviewed in terms of radiographic sagittal alignment and self-reported pain. RESULTS: Twenty patients were treated without realignment revision surgery. Twenty-eight patients were treated with anterior and posterior osteotomies and realignment with instrumentation. For patients originally fused to the sacrum, realignment averaged 12 cm. Pain was reduced from 7 to 3 (10-point scale). In patients fused to L4 or L5, realignment averaged 7 cm. Pain was reduced from 6 to 2. Magnetic resonance imaging revealed viable caudal discs in four patients who were consequently spared extension of fusion to the sacrum. CONCLUSIONS: Treatment without realignment surgery demonstrated long-term success in 27% of cases. The latter all had two intact discs below the previous fusion and sagittal malalignment less than 4 cm. Realignment surgery effectively reduced pain in patients failing a conservative approach.     

Oxygen in the field hospitals: current experience in the military health service]

A fifty per cent oxygen ratio locks quite sufficient for putting at sleep war wounded patient. After the present time, every french field surgical structures are equipped with oxygen extractors. Furthermore, those teams have at heir disposal for several years, oxygen generators, working with sodium chlorate candels. Those one can fill oxygen cylinders (3.5 l at 90 or 150 bars), providing pure oxygen, which will ever be essential under exceptional conditions. During war period, the supply difficulties demand to have at disposal two different production capabilities for oxygen administration.     

Time course evolution of ventilatory responses to inspiratory unloading in patients

Inspiratory muscle unloading decreases ventilatory drive. In this study, we examined the time course of this effect in patients with chronic obstructive pulmonary disease receiving two modes of ventilatory support: pressure support ventilation (PSV), during which each cycle was assisted, and biphasic positive airway pressure (BIPAP), set up in such a manner that one spontaneous breath took place between two consecutive pressure-assisted breaths. The first breath following the switch from spontaneous breathing to PSV was associated with an increase in tidal volume (VT) and a drop in mean transdiaphragmatic pressure (mean Pdi) and inspiratory work (WI) performed per liter but with unchanged values of esophageal occlusion pressure at 100 ms (Pes 0.1), diaphragmatic electrical activity (EMGdi), and WI performed by breath. The same phenomena were observed for the assisted breath of BIPAP as compared with the preceding spontaneous breath. During the subsequent breaths of PSV, Pes 0.1, EMGdi, and WI performed per breath decreased progressively up to the sixth to eighth breaths, and VT returned to pre-PSV values. We conclude that in patients with chronic obstructive pulmonary disease the decrease in ventilatory drive associated with PSV takes place from the first breath onwards but requires six to eight breaths to be fully achieved. During BIPAP, as a consequence of the kinetics of the PSV-induced downregulation of ventilatory drive, assisted breaths following spontaneous breaths are characterized by an enhanced inspiratory efficiency.     

Postoperative outcome of Crohn's disease in 30 children

BACKGROUND: Thirty children operated on for Crohn's disease (CD) were reviewed (1975-1994). The aim of the study was to assess their postoperative outcome. PATIENTS: 19 boys and 11 girls, aged 15.3 (2) years (range 11.3-20) at surgery were studied. RESULTS: Surgical indications were acute complications of CD and chronic intestinal illness. Six months after surgery, 11 of 12 patients had been weaned off steroids, and 22 of 23 patients were weaned off nutritional support; 17 patients without recurrence had a mean (SD) weight gain of 2.1 (8) kg and a height gain of 3.36 (3) cm. During 3.1 (2.7) years follow up, 12 patients (40%) had a recurrence of the disease after 19.4 (14) months (means (SD)): supra-anastomotic recurrence (six), severe perianal disease (two), and chronic illness (four). Six of 14 patients who were treated with mesalazine (13) or azathioprine (one) had recurrences. The postoperative recurrence rate was 50% at two years. CONCLUSION: Surgical treatment modifies the immediate outcome of severe or complicated CD, but does not prevent recurrence, despite localised resection or prophylactic postoperative treatment. Extension of the disease before surgery seems to be a major risk factor for postoperative recurrence in children.     

Practical guide for the use of bone mineral measurements in the assessment of treatment of osteoporosis: a position paper of the European foundation for osteoporosis and bone disease. The Scientific Advisory Board and the Board of National Societies

BACKGROUND: Nosocomial aspergillosis is a well known complication of immunosuppression in cancer patients and those undergoing transplantation and has usually been associated with major building construction or demolition. An observational study is reported of the hospital environment associated with an outbreak of aspergillosis in a paediatric oncology ward. METHODS: All cases of aspergillosis were identified from the hospital records and categorised as definite or probable according to the extent of supportive clinical and laboratory findings. All relevant aspects of building ventilation, air filtration, and aerosol generation considered relevant were examined and air samples for fungi were taken in triplicate at 25 sites using a slit sampler with appropriate culture media. RESULTS: Six cases of aspergillosis were identified over one year out of the 148 patients who attended the unit - the only part of the hospital where cases were found. Examination of the building services and function suggested that the cause or source was isolated to this paediatric oncology/haematology ward and may have been attributed to a defective disposal conduit door as well as the dispersal of a contaminated aerosol from the ward vacuum cleaner which had the highest measured concentrations of Aspergillus fumigatus in or around the building (65 colony forming units (cfu)/m3 compared with 0-6 cfu/m3 elsewhere). No further cases were identified in the two years after these hygiene arrangements were changed. CONCLUSIONS: The investigation of this outbreak of nosocomial aspergillosis identified several possible sources of fungally contaminated aerosol which could have been implicated as the cause. Their modification was followed by a reduction in the incidence of further cases. Each should be incorporated as an issue of importance in hospital building design and hygiene.