A QUANTITATIVE THEORY OF THE PRECIPITIN REACTION : VII. THE EGG ALBUMIN-ANTIBODY REACTION IN ANTISERA FROM THE RABBIT AND HORSE

1. In two rabbits subjected to prolonged injections with crystalline egg albumin the antibodies in one showed progressive changes such as noted in an earlier paper; the antibodies in the other did not. 2. The significance of this behavior in the production of sera for therapeutic use is pointed out. 3. Quantitative studies are reported on the low grade or incomplete antibody present in the early stages of immunization of a horse with egg albumin. 4. Quantitative studies on the flocculating antibody from later bleedings from the horse are given, and the dissociation of the soluble pre-zone compounds by rabbit anti-egg albumin is studied. Rough velocity estimations are reported. 5. The bearing of the findings on the mechanism of precipitin and flocculation reactions and of the Danysz effect is discussed in terms of the union of multivalent antigen with multivalent antibody.     

Million Behavioral Health Inventory: its utility in predicting physical function in patients with low back pain

The present study evaluated the use of psychologic measures, in particular, the relatively new Million Behavioral Health Inventory (MBHI), in predicting change in physical function of chronic low back pain patients undergoing a functional restoration program. The first 134 consecutive patients completing this program were assessed. Results demonstrated that various clinical scales of the MBHI were predictive of improvement in physical function. In addition, various scales enabled discrimination between patients who completed the program and those who prematurely dropped out. Although this inventory shows promise in helping to predict response to treatment, no single psychologic test can reliably be used as the sole predictor in clinical cases.     

Long-term treatment with sildenafil in chronic thromboembolic pulmonary hypertension.

For chronic thromboembolic pulmonary hypertension not amenable to pulmonary endarterectomy, effective medical therapy is desired. In an open-label uncontrolled clinical trial, 104 patients (mean +/- sem age 62 +/- 11 yrs) with inoperable chronic thromboembolic pulmonary hypertension were treated with 50 mg sildenafil t.i.d. At baseline, patients had severe pulmonary hypertension (pulmonary vascular resistance 863 +/- 38 dyn.s.cm(-5)) and a 6-min walking distance of 310 +/- 11 m. Eight patients were in World Health Organization functional class II, 76 in class III and 20 in class IV. After 3 months' treatment, there was significant haemodynamic improvement, with reduction of pulmonary vascular resistance to 759 +/- 62 dyn.s.cm(-5). The 6-min walking distance increased significantly to 361 +/- 15 m after 3 months' treatment, and to 366 +/- 18 m after 12 months' treatment. A subset of 67 patients received a single dose of 50 mg sildenafil during initial right heart catheterisation. The acute haemodynamic effect of this was not predictive of long-term outcome. In this large series of patients with inoperable chronic thromboembolic pulmonary hypertension, open-label treatment with sildenafil led to significant long-term functional improvement. The acute effect of sildenafil may not predict the long-term outcome of therapy.     

Simultane Radiochemotherapie mit intraluminaler HDR-Brachytherapie des Ösophaguskarzinoms

PURPOSE: To study efficacy and toxicity of radiochemotherapy in esophageal cancer including initial endoluminal high-dose-rate brachytherapy (HDR-BT). PATIENTS AND METHODS: Between 01/1995 and 06/2005, 61 patients with esophageal cancer were treated preoperatively with definitive and palliative intent. Treatment started with intraluminal HDR-BT for recanalization of the esophagus (single fraction size of 8 Gy in 0.5 cm depth, three times, q7d) followed by external-beam radiation therapy (50 Gy total dose, 5 x 2 Gy/week, 25 fractions in 5 weeks). Chemotherapy was started simultaneously with external irradiation (three courses of cisplatin and 5-fluorouracil, q21d). RESULTS: Swallowing function improved in 55/61 patients (dysphagia classification according to the RTOG), and worsened in 6/61 patients, respectively. Median duration of symptomatic improvement was 11 months, median follow-up 12 months (range 3-68 months). Following simultaneous radiochemotherapy, tumor resectability was achieved in 7/25 patients of the neoadjuvant group, and the histological specimen showed complete remission in 6/7 patients. CONCLUSION: These results indicate a favorable effect of simultaneous radiochemotherapy starting with endoluminal HDR-afterloading-( AL-)BT in esophageal cancer.     

Physical-activity-assessment measures compared in a biethnic rural population: the San Luis Valley Diabetes Study

We evaluated the consistency of three questionnaire methods of assessing work and leisure activity in the rural biethnic population of the San Luis Valley Diabetes Study. A 7-d physical activity recall (PAR), a ranking of usual activity, and a history of usual participation in vigorous activity were used. Energy expenditure (kJ.kg-1.wk-1) (EE) was estimated from PAR. Subjects were 503 adults [49% non-Hispanic white (NHW), 51% Hispanic]. Physical activity at work rather than leisure-time activity largely determined total energy expenditure. Average EE at work increased with work rank for all subjects combined [mean EE (SEE) for rank 1 (low) = 324.2 (24.4), rank 4 (high) = 874.0 (102.1)] and within sex, ethnic, and occupational subgroups. Leisure EE increased with leisure rank only for NHW men and employed women. Similar patterns were observed in comparisons of PAR data with history of vigorous activity. Further development and validation of instruments appropriate for use across population subgroups are needed.     

Intracardiac transplantation of a mixed population of bone marrow cells improves both regional systolic contractility and diastolic relaxation.

BACKGROUND: Pre-clinical and clinical studies suggest that transplantation of bone marrow-derived stem cells can improve global cardiac function. However, no quantitative assessment of regional systolic contraction and correlation with phenotype has been made. Therefore, we used our model of cryoinfarcted rabbit myocardium for intracardiac transplantation of a mixed population of bone marrow-derived cells and assessed both regional function and myogenic conversion of the cells. METHODS: Nineteen New Zealand white rabbits underwent cryoinjury of the left ventricle. Autologous bone marrow (BM) cells were expanded in vitro. After 2 weeks, either 1 x 10(8) mixed BM-derived progenitor cells (BM group, n = 11) or vehicle (control group, n = 8) were injected into the cryoinjured region. Regional systolic function was measured using micromanometry and sonomicrometry before and 4 weeks after cell injection; cell phenotype was evaluated histologically. RESULTS: All animals in the BM group significantly improved both systolic shortening (0.11 +/- 0.7 vs -0.05 +/- 0.05 mm in the control group, p < 0.05) and regional stroke work when compared with control (9.6 +/- 2.4 vs -1.2 +/- 1.2 mm . mm Hg, p < 0.003). In addition, the BM group had improved global diastolic function, as measured by minimum dP/dt and end-diastolic pressure. On histologic assessment, BM cells differentiated toward a myogenic phenotype. CONCLUSIONS: Transplanting a mixed population of marrow-derived cells that can adopt a myogenic phenotype improves regional contractility and diastolic relaxation after myocardial infarction.     

Expression of epithelial matrix molecules collagen and laminin and corresponding integrins in chronic wounds

Re-epithelialization of cutaneous wounds is a coordinated process of proliferation and migration of keratinocytes at the wound edge. The study objective was to identify the differences in epidermal morphology, keratinocyte proliferation and matrix molecules (laminin 1, laminin 5, type IV collagen) and their specific integrin (α3, α6) expression in biopsies of meshed split thickness grafted and chronic wounds. The mean mitotic index of keratinocytes (ratio of cell cycle associated antigen Ki-67 expressing keratinocytes to basal keratinocytes) was highest in chronic wounds (38.7%) compared to acute wounds (22.25%, range 5.7% to 54%). The mean thickness of the hyper-proliferative epithelium at the wound edge of chronic wounds was 0.69 mm compared to 0.15 mm at the wound margin of split thickness grafted wounds. Both chronic wounds and skin grafted wounds exhibited strong laminin 5 immunoreactivity at the basal side of the epithelium, which extended under the most forward keratinocytes. Laminin 1 and type IV collagen immunoreactivity did not extend to the wound margin in either skin grafted or chronic wounds. In both transplanted skin and chronic wounds, the integrin sub-units α3 and α6 exhibited a strong pericellular immunoreactivity on the leading keratinocytes of the wound margin. Our data demonstrates that the proliferation of keratinocytes and the expression of associated integrins are not impaired in chronic wounds. Presented at the 33rd Congress of the Association of German Plastic Surgeons, Germany, 18–21 September, 2002.     

Dual ligand binding of pyridylalkanamides to microsomal cytochrome P-450

Twelve homologous and regioisomeric pyridylalkanamides were examined spectrally for their binding affinity to cytochrome P-450 in phenobarbital- and 3-methylcholanthrene-induced rat liver microsomes. The pKs values were calculated by the Lineweaver-Burk method and by non-linear analysis using both a one ligand-one acceptor and a one ligand-two acceptor model. The latter model best fits most of the data, confirming that two pKs values exist for most derivatives in the 3-pyridyl and 4-pyridyl series. Structure-binding relationships are discussed. The two binding constants are hypothesized to arise from a dual mode of binding to the ferric ion. At low ligand concentrations, binding to hexacoordinated cytochrome P-450 occurs and involves displacement of an endogenous 6th ligand; at higher concentrations, the ligands bind to the pentacoordinated P-450, resulting in a high-to-low spin shift.     

Protease and plasminogen activator activity in human bladder carcinoma

The ability of human bladder tissue extracts to cleave 14C-labelled globin in the absence and in the presence of plasminogen was assayed to quantify non-specific protease and plasminogen activator (PA) activity, respectively. In normal human bladder tissue the non-specific protease activity was approximately 2-fold higher than in tissue samples obtained from transitional cell carcinoma of the bladder (TCC). In contrast, PA activity was almost 4-fold higher in TCC than in normal transition cell epithelium. Acid-treated urine from 19 patients with TCC of the bladder exhibited significantly higher levels of plasminogen activator activity than similarly treated urine from controls. These results indicate that malignant transformation of the bladder epithelial tissue results in elevated levels of PA in the tissue and in urine. Further studies are needed to assess the potential of PA determination in the management of bladder cancer patients.