Misoprostol for primary versus secondary prevention of postpartum haemorrhage: a cluster-randomised non-inferiority community trial.

OBJECTIVE: To assess whether secondary prevention, which preemptively treats women with above-average postpartum bleeding, is non-inferior to universal prophylaxis. DESIGN: A cluster-randomised non-inferiority community trial. SETTING: Health sub-centres and home deliveries in the Bijapur district of Karnataka, India. POPULATION: Women with low-risk pregnancies who were eligible for delivery with an Auxiliary Nurse Midwife at home or sub-centre and who consented to be part of the study. METHODS: Auxiliary Nurse Midwifes were randomised to secondary prevention using 800 mcg sublingual misoprostol administered to women with postpartum blood loss ≥350 ml or to universal prophylaxis using 600 mcg oral misoprostol administered to all women during the third stage of labour. MAIN OUTCOME MEASURES: Postpartum haemoglobin ≤7.8 g/dl, mean postpartum blood loss and postpartum haemoglobin, postpartum haemorrhage rate, transfer to higher-level facilities, acceptability and feasibility of the intervention. RESULTS: Misoprostol was administered to 99.7% of women as primary prevention. In secondary prevention, 92 (4.7%) women had postpartum bleeding ≥350 ml, of which 90 (97.8%) received misoprostol. The proportion of women with postpartum haemoglobin ≤7.8 g/dl was 5.9 and 8.8% in secondary and primary prevention clusters, respectively [difference -2.9%, one-sided 95% confidence interval (CI) <1.3%]. Postpartum transfer and haemorrhage rates were low (<1%) in both groups. Shivering was more common in primary prevention clusters (P = 0.013). CONCLUSION: Secondary prevention of postpartum haemorrhage with misoprostol is non-inferior to universal prophylaxis based on the primary outcome of postpartum haemoglobin. Secondary prevention could be a good alternative to universal prophylaxis as it medicates fewer women and is an acceptable and feasible strategy at the community level. TWEETABLE ABSTRACT: Secondary prevention of postpartum haemorrhage with misoprostol is non-inferior to universal prophylaxis.

Dorsal capsuloplasty for dorsal instability of the distal ulna.

Background Dorsal instability of the distal ulna can lead to chronic wrist pain and loss of function. Structural changes to the dorsal radioulnar ligaments (DRUL) of the triangular fibrocartilage complex (TFCC) and the dorsal capsule around the ulnar head with or without foveal detachment can lead to volar subluxation of the distal radius e.g., dorsal instability of the distal ulna. Purpose Is to evaluate the post-operative results of reinstituting distal radioulnar joint (DRUJ) stability through reefing of the dorsal capsule and dorsal radioulnar ligaments, with and without a foveal reattachment of the TFCC. Methods A total of 37 patients were included in this retrospective study. Diagnosis and treatment was based strictly on dry wrist arthroscopy. In 17 patients isolated reefing of the DRUL and their collateral tissue extension was performed. In 20 patients an additional foveal reinsertion was performed. Postoperative results were evaluated with the DASH questionnaire, VAS scores, grip strength and range of motion. These findings were extrapolated in the Mayo wrist score. The two subgroups were compared. Results Mayo wrist scores of the whole population had a mean of 73. There was no difference between the group that was treated with reefing of the DRUL only and the group that was treated with a combined foveal reinsertion. Conclusion This relatively simple 'dorsal reefing' procedure, with foveal reinsertion when indicated, is a reliable method to restore volar-dorsal DRUJ stability with a significant decrease in pain sensation, good DASH scores and restoration of functional grip strength and ROM. Type of Study/Level of Evidence Therapeutic, Level IV.

Inter-carpal soft tissue entrapment. A possible explanation for chronic dorsal wrist pain.

This retrospective study evaluates the surgical treatment of a group of patients with unknown chronic dorsal wrist pain. The cause of their symptoms was interpreted as a painful entrapment of fibrous tissue in the radio-carpal and inter-carpal joints during specific movements. Between 1997 and 2001, 30 patients were treated by surgical excision of this tissue and 26 patients were traced for follow-up. Twenty-three patients were symptom free, or experienced major benefit from surgery. Wrist function measurements using the VAS scale showed improvement in 24 patients. Microscopic examination of the removed specimen shows fibrous tissue with non-specific changes. Inter-carpal soft tissue entrapment can explain the typical clinical findings in some patients with unknown chronic dorsal wrist pain. After careful selection, surgical excision of all entrapped tissue in the radio-carpal and mid-carpal joint may give relief of pain and improvement of wrist function.

[Favorable results of surgical treatment of mucoid cysts of the fingers and thumb in 20 patients, Leyenburg Hospital, Den Haag, 1992-99]. / Gunstige resultaten van chirurgische behandeling van mucoïdcysten aan vingers en duim bij 20 patiënten, Ziekenhuis Leyenburg, Den Haag, 1992/'99.

OBJECTIVE: Evaluation of the surgical treatment of mucoid cysts of the fingers and thumb. DESIGN: Retrospective, descriptive. METHOD: In 20 patients admitted to the Leyenburg Hospital in the Hague during the period 1992/'99, 24 mucoid cysts were treated by surgical excision and simultaneous removal of any pre-existing joint irregularities (osteophytes). Relevant data were collected after an average follow-up period of 2.5 years (range: 3 months-8 years) by a review of the charts, a physical examination and a questionnaire. RESULTS: The 20 patients included 13 women and 7 men with an average age of 74 years (range: 42-84). On follow-up examination they reported decreased pain in 8 of the 10 previously painful fingers and improved function in 8 of the 9 fingers with previous function limitation. Physical examination revealed an improvement in digital excursions in 8 of the 9 patients with a pre-operative function limitation and a decreased mobility in 18 of the 24 cysts. Nail abnormalities had been present in 11 patients; these all disappeared following the operation. Of the 20 patients, 17 were very and 3 were moderately satisfied with the results of the operation. No recurrences were seen during the follow-up period. CONCLUSION: The results of the surgical technique used were: no recurrences, no more pain or restricted movement in most patients. Other symptoms, such as longitudinal groove in the nail, recurrent discharge of the cyst and cosmetic imperfections, were counteracted successfully.

Real-time analysis of immunogen complex reaction kinetics using surface plasmon resonance.

Real-time biospecific interactions of immunogens, measured via BIAcore, were used to verify qualitatively a biosensor design which relies on analyte binding competition reactions to open cross-linked receptor channels. The complexes of importance are: (1) cardiac troponin I (TnI) and monoclonal mouse anti-TnI IgG mAb 265, (2) TnI and bispecific antibodies (BsAbs) which on one end recognize TnI while the other end recognizes nicotinic acetylcholine receptors (nAChRs), (3) nAChRs and rat anti-nAChR IgG mAb 148, (4) nAChRs and BsAbs, (5) nAChRs and Fab'148-TnI biopolymers, and (6) mAb 265 and Fab-TnI biopolymers. A commonly used sensor chip, CM5, was employed to immobilize TnI by covalent amine coupling, while bilayer membrane-associated protein, nAChR, was noncovalently sequestered on a HPA sensor chip via hydrophobic adsorption of membrane lipids. The epitopes of membrane-bound nAChRs were still available to immunogens after being immobilized. Kinetic rate constants and affinities of these systems were calculated from BIAcore sensorgrams. The order of magnitude for dissociation rate constants of the BsAb/TnI linker complex and biopolymer/mAb 265 complex is 10(-2) s-1, which provides an opportunity for competitive binding of free analyte in the sensing systems.

Preparation and characterization of bifunctional biopolymers for receptor-based liposomal immunosensing.

In this study, we prepared bifunctional biopolymers for development of a novel liposomal immunosensing element. These biopolymers were produced such that a rat monoclonal antibody fragment Fab' was linked to a cardiac protein Troponin I (TnI) peptide by a cross-linking reagent, o-phenylenedimaleimide (o-PDM) or N-sucinimidyl 3-(2-pyridyldithio)propionate (SPDP). The biopolymer formation yields were approximately 10% for Fab-TnIMal and 30% for Fab-TnISPDP. Molar ratios of Fab' to SPDP or o-PDM and conjugated Fab' to TnI peptide and conjugation pH have considerable effects on the biopolymer yield. Purification of these biopolymers was achieved by employing size-exclusion HPLC. These biopolymers can bind to receptor channels on one end, while the peptide end can be recognized by an anti-TnI antibody serving as a protein linker to block the channels in the immunosensing element. Then reactions may be used where free analyte competes for cross-linker binding sites whereby channels are rendered active. Characterization of purified biopolymers was performed using gel electrophoresis, ELISAs, and a BIAcore instrument. Furthermore, results of real-time biospecific interaction experiments with use of the BIAcore show that competition binding reactions of free TnI peptide occurred in this new immunosensing design. The binding activities of these two biopolymers are slightly different.

Kinetic modeling and analysis of a vesicle system for immunosensor development.

A novel mechanism is presented for immunosensor development that uses an immunological competition reaction in a vesicle system. This system consists of a suspension of reconstituted vesicles, channel agonist, protein linker to block the channels, voltage sensitive dye and analyte to be detected. In the proposed mechanism analyte serves a catalytic role as individual analytes competitively displace multiple channel linkers through association with one channel, dissociation and new associations with other channels. When one channel opens on a vesicle a permanent Nernst potential develops for that vesicle leading to fluorescence of voltage sensitive dyes. The time constant of the redistribution from linker-channel form to analyte-channel form is 0.92/k4 (k4 is the off-rate constant for the analyte-channel association) in the region of analyte concentrations less than 10(-9) M. Kinetic analyses show that several factors, including concentration of analyte or linker, number of channels per vesicle, on-rate or off-rate constant of the linker-channel and on-rate constant of analyte-channel complexes have significant effects on the minimum signal response time.

A highly stable and selective biosensor using modified nicotinic acetylcholine receptor (nAChR).

Methods for developing stable, sensitive and selective bilayer lipid membrane (BLM)-based biosensors are discussed. Stable BLMs were formed over micromachined polyimide apertures. Selective sensors were made by incorporating nicotinic acetylcholine receptors (nAChRs) modified with bispecific antibodies (BsAbs). When two BsAbs, attached to one nAChR, encounter antigen (Ag), channels are blocked. Sensitivity to single Ag molecules would be possible by monitoring closure of individual nAChRs.

Fatal intoxication with amlodipine.

Although poisoning with calcium channel blocking agents is frequent, to our knowledge no cases involving amlodipine have been published. We describe here a case of amlodipine intoxication, in which protracted hypotension did not respond to vasopressor therapy alone. After the addition of continuous calcium chloride and glucagon infusion, blood pressure was restored and vasopressor therapy could be tapered off substantially. When calcium and glucagon were interrupted because of severe hypercalcemia and hyperglycemia, the patient developed irreversible hypotension and died. Either glucagon or calcium or both, and to some extent vasopressors, seem to have constituted effective treatment of hypotension in this case.

[Good results with the surgical treatment of trigger finger (tendovaginitis stenosans)]. / Goede resultaten met chirurgische behandeling van de knappende vinger (tendovaginitis stenosans).

Stenosing tendovaginitis (trigger finger) may be treated surgically or conservatively. Surgical incision of the proximal part of the flexor tendon sheath in 100 patients (91 adults and 9 children) proved a reliable method. In 97 patients the resistance was abolished by surgical treatment, with good functional results. It is a simple procedure, with hardly any complications and a short follow-up period.

Basal membrane uptake in potassium-secreting cells of midgut of tobacco hornworm (Manduca sexta).

Basal membrane voltage (Vb), intracellular K+ activity [(K+)i], and short-circuit current (Isc) were measured in isolated posterior midguts of Manduca sexta wherein Isc is a measured of active secretion of K+ from blood into lumen. When bathed in 32 mM K+ and exposed to 100% O2, average values were Isc = 244 microAmp/cm2, Vb = -33.1 mV, and (K+)i = 88.6 mM. The electrochemical gradient across the basal membrane (d mu) averaged +5.8 mV (a gradient favorable for K+ entry). Exposure to 5% O2 led to a new steady state in which Isc = 71 microAmp/cm2, Vb = -18.7 mV, and (K+)i = 99.4 mM. During hypoxia, d mu averaged -9.9 mV (a gradient unfavorable for K+ entry). When the external bathing solution was 10 mM K+, comparable values were, for 100% O2, Isc = 139 microAmp/cm2, Vb = -56.1 mV, (K+)i = 72.2 mM, and d mu = +3.6 mV, and in 5% O2 the values were Isc = 28.3 microAmp/cm2, Vb = -43.7 mV, (K+)i = 76.1 mM, and d mu = -10.2 mV. The failure of cellular K+ to fall during prolonged hypoxia is evidence for a thermodynamically active basal K+ uptake process.

Active chloride transport in isolated posterior midgut of tobacco hornworm (Manduca sexta).

The short-circuited posterior midgut of larval tobacco hornworm (Manduca sexta) actively transports Cl- from lumen to hemolymph as measured by unidirectional fluxes of 36Cl-. Potentials and Cl- activities in cytosol and goblet cavity were measured using double-barreled Cl--selective microelectrodes. In the short-circuited tissue, the goblet cavity was electrically positive to the bathing solution, and Cl- activity was below electrochemical equilibrium with luminal fluid. The cytosol was electrically negative to the bathing solution, and Cl- activity was above electrochemical equilibrium. Thus Cl- is pumped from goblet cavity into cell. Although the Cl- that is pumped into the cell can cross the basal membrane, its Cl- conductance is quite low. The Cl- conductance is also quite low in apical membranes of columnar cells. Depression of intracellular Cl- after exposure of the luminal side to high HCO-3 suggested that these membranes have a Cl- for HCO-3 exchange mechanism. The paracellular pathway for Cl- comprises approximately 10% of the total transepithelial conductance.

Relaxation-induced contraction of smooth muscle surrounding hamster ovarian follicles.

Changes in intrafollicular pressure and follicular diameter resulting from injecting or withdrawing fluid from the antrum were measured in preovulatory follicles and used as an assay for changes in tension in the follicular wall by applying the Laplace relationship for thin-walled spheres. Passive length-tension curves were constructed from pressure-volume measurements to establish baseline wall stiffness. Any subsequent change in pressure could then be compared to the length-tension curves to evaluate whether it arose from active tension development or from passive stretch. When intact follicles (1-2h before ovulation) were subjected to release of passive stretch, they exhibited a contractile response that lasted 15 sec-2 min and was characterized by cyclic increases and decreases in tension, with a period of 1 cycle every 2-3 sec. The probability of activating a response in the tissue was most strongly correlated with the rate of release of passive stretch. Intrafollicular pressures generated during active contractile responses sometimes reached 80 mmHg (10.64 mPa), corresponding to a wall tension of 5332 dynes/cm (5.332 N/m) (for a 1 mm follicle) and were clearly well above the passive length-tension curves. Passive stretching of the follicular wall during a contractile response to 5-hydroxytryptamine stimulation resulted in large reductions in active wall tension for the duration of the stretch. These results are consistent with a stretch-activated inhibition of contractile events.

Barium modifies the concentration dependence of active potassium transport by insect midgut.

The rate of active K+ transport by the isolated lepidopteran midgut shows a rectangular hyperbolic relation to [K+] over the range 20 to 70 mM K+ in the absence of any divalent cation. Addition of Ba++ to the hemolymph (K+ uptake) side introduces a linear component to the concentration dependence, such that active K+ transport is decreased at [K+] of 55 mM or less, but increased transiently at higher [K+]. As [Ba++] is increased over the range 2 to 8 mM the linear component increases and the saturating component decreases; in 8 mM Ba++ the concentration dependence is dominated by the linear component. The effect of Ba++ cannot easily be accounted for by simple competition with K+ for basal membrane uptake sites. Similar effects might be exercised by other alkali earth cations, since the concentration dependence of active K+ transport possesses a substantial linear component in solutions containing 5 mM Ca++ and 5 mM Mg++ (the alkali earth metal concentrations of standard lepidopteran saline).

Growth of body protein, fat, and skeleton in steers fed on three planes of nutrition.

The growth of body protein, fat, and skeleton of growing steers was determined from published experimental data of steers fed three planes of nutrition. Each animal was partitioned into: 1) metabolically slow tissue which included hide, hooves, horns, skeleton, and fat, and 2) metabolically active tissue (MAT) which were the remaining tissues. MAT grew exponentially in time and approached the same final value for all planes of nutrition; however, growth rates depended on energy intake. The mass of active tissues was described by MATkg = 27 + 393 (1 - e-t/tau) where t and tau are in months; tau was 25.8, 46.7, and 57.4 months for the high, medium, and low planes of nutrition, respectively. The finding that MAT retained the same mathematical form but grew more slowly on the lower nutritional planes suggests that changes in energy set the scale of physiological age. Fat deposition was linear with time for all groups, although the rates depended on energy intake. The rates were 8.21, 2.08, and 1.29 kg/month for the high, mediu, and low planes of nutrition, respectively. The results suggest that steers are not programmed to synthesize protein first and then fat only with the remaining energy; rather the level of energy intake and the age determine how the ingested energy is partitioned into protein and fat synthesis.