Porous implants for knee joint meniscus reconstruction: a preliminary study on the role of pore sizes in ingrowth and differentiation of fibrocartilage

Implants with four different macropore sizes were implanted in the meniscus of 29 rabbits for assessment of ingrowth and differentiation of fibrocartilage. Implant macropores were 50-90, 90-150, 150-250 and 250-500 mum, the vol.% macropores was 48-55 and total pore volume 84-86 vol.%. Ingrowth was optimal in the two large pore implants whereas the small pore implants partially remained empty up to 1 year post-operative. Capsule formation and the foreign body reaction was severe for the small pore implants whereas this occurred to a lesser extent in the two large pore implants. Fibrocartilage formation, as assessed by morphology and antibody labelling for type I and type II collagen, was observed in a similar way in all implant types. It is concluded that for optimal ingrowth and incorporation of partial or total meniscal prosthesis, macropore sizes must be in the range of 150-500 mum.     

Pharmacokinetic studies with mecillinam and pivmecillinam.

Mecillinam (FL 1060) is a new beta-lactam antibiotic particularly active against gram-negative organisms. When given intravenously, very high serum levels were maintained for a short period of time. Lower peak levels but comparable bioavailability were obtained after intramuscular administration. Gastrointestinal absorption of mecillinam is poor, and for effective oral therapy the drug must be given in the form of its pivaloyl-oxymethyl ester pivmecillinam (FL 1039) which is well absorbed and rapidly transformed to mecillinam by enzymatic hydrolysis in the body. Urinary recovery of mecillinam after orally administered pivmecillinam was 45% in the first 6 h compared with 55 and 59% after mecillinam given by the intravenous and intramuscular routes, respectively. By increasing the dose the orally active ester produced proportionally higher levels of mecillinam, and the area under the serum curve was doubled with the dose. Higher peak levels and prolonged maintenance of high serum concentrations were seen after administration of pivmecillinam with probenecid. The presence of food in the stomach did not influence the absorption of pivmecillinam to any great extent.     

Well‐being and cerebral oxygen saturation during acute heart failure in humans

Cerebral symptoms and near‐infrared spectrophotometry‐determined cerebral oxygen saturation (ScO₂) were followed in patients treated for normotensive acute congestive heart failure. The reproducibility and normal range for ScO₂ were established from 39 resting subjects without cardio‐respiratory disease: the ScO₂ ranged from 55 to 78% with a coefficient of variation for triple determination of 6%. Patients rated cerebral symptoms on a scale with end‐points of 0 (best) and 10 (worst). In eight patients with acute heart failure, arterial oxygen tension increased during decongestive treatment, from 9·1 (4·9–10) to 10·4 kPa (7·3–17); median with range, as did arterial oxygen saturation, from 94 (48–97) to 97% (87–99) (P<0·02), whereas the mean arterial pressure, heart rate and arterial carbon dioxide tension remained unchanged. The cerebral symptom score improved from 8 (3–10) to 1 (1–9) and the ScO₂ increased from 34 (20–58) to 50% (19–91) (P<0·02). A ninth patient presented with a silent but massive myocardial infarction: she was cerebrally obtunded with a ScO₂ of 18% and soon died. In patients with normotensive acute heart failure and cerebral symptoms, cerebral oxygen saturation is low, and during successful treatment ScO₂ increases with the well‐being of the patient.     

Estimation of total body composition from single photon absorptiometry measurement of forearm fat content

The forearm fat content (FATarm, measured by single photon (125I) absorptiometry) and the 24-h urinary creatinine excretion (24 Ucrea) were determined in 29 healthy adults (12 males and 17 females), whose total body fat percentage was measured by three different methods: (i) Dual photon (153Gd) absorptiometry (DPA); (ii) body density measurements (BD); and (iii) total body potassium determinations (TBP). Lean body mass (by DPA, BD, and TBP) correlated significantly with 24 Ucrea (r = 0.87-0.89, standard error of estimate (SEE) = 5.2-6.3 kg). The total body fat percentage could be predicted from FATarm with SEEs at 3.4-5.8 (r = 0.85-0.88) and from 24 Ucrea + body weight with SEEs at 5.1-7.5 (r = 0.61-0.72). We conclude that the FATarm measurement represents a new tool for simple assessment of body composition on a group basis.     

Brain and muscle oxygen saturation during head-up-tilt-induced central hypovolemia in humans

Summary. Near-infrared spectrophotometry-determined cerebral (ScO₂) and muscle oxygen saturations (SmO₂) were followed in 15 volunteers during passive 50° head-up-tilt-induced central hypovolaemia, and in nine volunteers during ventilatory manoeuvres affecting arterial carbon dioxide tension. During head-up tilt, mean arterial pressure [MAP, 88 (77–118) to 97 (80–136) mmHg, median and range] and heart rate [HR; 66 (49–77) to 87 (42–132) beats min^-1 P<0.01] increased, but after 22 (1–45) min they declined [to 61 (40–91) mmHg and 69 (38–109) beats min^-1, respectively, P=0.001] and pre-syncopal symptoms developed. Central hypovolaemia was indicated by an increased thoracic electrical impedance, and a decreased cardiac output and central venous oxygen saturation. The arterial oxygen saturation, pulmonal oxygen uptake and skin temperatures remained constant. The ScO₂ remained stable at 72 (62–77)% until the pre-syncopal incidence, when it decreased to 62 (31–73)% (P=0–001), and tilt down made it increase to 75 (36–87)% (P<0.05) before the recovery value was established. In contrast, SmO₂ decreased during tilting [75 (70–87) to 65 (53–70)%], and recovered to 70 (53–83)%, P<0.01) during the hypotensive episode. The end-tidal CO₂ tension decreased only during tilt-up. The ScO₂ decreased, and SmO₂ increased during hyperventilation, and ScO₂ increased during breathing of 5% carbon dioxide. Rebreathing from a bag made SmO₂ decrease and resulted in a biphasic ScO₂ response: it first increased and subsequently decreased. Cardiovascular changes during tilt were not reflected in skin temperature. The ScO₂ reflected the maintained autoregulation of cerebral blood flow until the perfusion pressure decreased markedly. In contrast, SmO₂ mirrored muscle vasoconstriction early during tilt, and vasodilatation when pre-syncopal symptoms appeared.     

Mild mental stress in diabetes: changes in heart rate and subcutaneous blood-flow

Summary. A TV-game of tennis of 20 min duration was used to study the influence of mild mental stress on subcutaneous blood-flow (SBF), blood-pressure and heart rate in nine insulin-dependent diabetics and nine healthy subjects. SBF was measured on the thigh by local clearance of xenon-133. Measurements were made before, during and after the period of stress. During stress, SBF increased significantly by 26% in the healthy subjects, while SBF remained unchanged in the diabetics. The difference between the two groups was significant (P<0–05). Following stress, SBF returned to pre-stress level in the healthy subjects, while a significant decrease of 33% was observed in the diabetics. The pre-stress heart rate level was higher and the stress-induced increase in heart rate was less in the diabetics compared with the healthy subjects (P<005). During the stress a slight–but insignificant–increase in blood-pressure was observed in both groups. In conclusion, we found that even mild mental strain influences SBF in both normal subjects and in diabetics. The induced alterations in the two groups are different, probably because of a slight parasympathetic dysfunction in the diabetics.     

Calcium utilization coupled to stimulation of postjunctional alpha-1 and alpha-2 adrenoceptors in isolated human resistance arteries.

Human s.c. resistance arteries (internal diameters 158-353 microns) were mounted in a microvascular myograph, and experiments were designed to examine the calcium pools utilized by selective stimulation of alpha-1 and alpha-2 adrenoceptors. In a concentration-dependent manner, phenylephrine and B-HT 933 evoked contractions mediated by alpha-1 and alpha-2 adrenoceptors, respectively, both in calcium-containing and in calcium-free saline. With respect to the maximum response to potassium in calcium-containing saline, the maximum responses to phenylephrine and B-HT 933 were 96 +/- 6 and 85 +/- 8%, respectively, in calcium-containing saline, and 79 +/- 4 and 14 +/- 2%, respectively, in calcium-free saline. A qualitatively similar difference in maximum responses to alpha-1 vs. alpha-2 adrenoceptor stimulation in calcium-free saline was demonstrated for norepinephrine in the presence of antagonists selective for the two alpha adrenoceptor subtypes. The maximum relaxation in calcium-containing saline produced by the calcium antagonist nitrendipine was 52 +/- 3% in vessels precontracted with phenylephrine, but 80 +/- 5% in vessels precontracted with B-HT 933. A quantitative difference in receptor reserves was demonstrated between alpha-1 and alpha-2 adrenoceptors; 90% of the maximum response was obtained at 34 +/- 5 and 57 +/- 8% receptor occupation, respectively. These data suggest that compared to responses mediated by stimulation of postjunctional alpha-1 adrenoceptors, stimulation of postjunctional alpha-2 adrenoceptors relies heavily on calcium influx. Stimulation of postjunctional alpha-2 adrenoceptors is, however, also coupled to intracellular release of calcium in isolated human s.c. resistance arteries.     

Plasma citrate during submaximal and intermittent supramaximal exercise

Plasma citrate was determined in seven subjects working 45 min at 50-60% of their maximal aerobic power and in six subjects who were exercised intermittently for five periods of 1 min at supramaximal work loads. Determinations of plasma lactate, glucose, free fatty acids and insulin were carried out simultaneously. During submaximal work the mean plasma citrate concentration decreased from 116 +/- 4 mumol/1 at rest to 108 +/- 5 mumol/1 after 10 min exercise (P less than 0.05) and increased above resting level to 136 +/- 5 mumol/1 40 min after cessation of work (P less than 0.05). During intermittent supramaximal exercise, mean plasma citrate concentration rose after the third work period and during recovery from 117 +/- 6 mumol/1 at rest to 181 +/- 9 mumol/1 40 min after last work period (P less than 0.05). Plasma citrate varied similarly to variations in plasma free fatty acids and inversely to changes of lactate concentrations during submaximal exercise. Opposite interrelationships were demonstrated during intermittent supramaximal exercise. Plasma citrate concentration varied in the same way as might be expected for changes in cytosolic citrate levels of muscle from in vitro knowledge of the regulatory role of citrate on glucose oxidation.     

Prediction of specific pathogens in patients with sepsis: evaluation of TREAT, a computerized decision support system

BACKGROUND: Prediction of bacterial infections and their pathogens allows for early, directed investigation and treatment. We assessed the ability of TREAT, a computerized decision support system, to predict specific pathogens. METHODS: TREAT uses data available within the first few hours of infection presentation in a causal probabilistic network to predict sites of infection and specific pathogens. We included 3529 patients (920 with microbiologically documented infections) participating in the observational and interventional trials of the TREAT system in Israel, Germany and Italy. Discriminatory performance of TREAT to predict individual pathogens was expressed by the AUC with 95% confidence intervals. Calibration was assessed using the Hosmer-Lemeshow goodness-of-fit statistic. RESULTS: The AUCs for Gram-negative bacteria, including Pseudomonas aeruginosa, Acinetobacter baumannii, Klebsiella spp. and Escherichia coli, ranged between 0.70 and 0.80 (all significant). Adequate calibration was demonstrated for any Gram-negative infection and individual bacteria, except for E. coli. Discrimination and calibration were acceptable for Enterococcus spp. (AUC 0.71, 0.65-0.78), but not for Staphylococcus aureus (AUC 0.63, 0.55-0.71). The few infections caused by Candida spp. and Clostridium difficile were well predicted (AUCs 0.74, 0.54-0.95; and 0.94, 0.88-1.00, respectively). The coverage with TREAT's recommendation exceeded that observed with physicians' treatment for all pathogens, except Candida spp. CONCLUSIONS: TREAT predicted individual pathogens causing infection well. Prediction of S. aureus was inferior to that observed with other pathogens. TREAT can be used to triage patients by the risk for specific pathogens. The system's predictions enable it to prescribe appropriate antibiotic treatment prior to pathogen identification.