BRCA1 gene therapy reduces systemic inflammatory response and multiple organ failure and improves survival in experimental sepsis.

Sepsis-related complications and mortality remain a major clinical problem. Increased cell death and unresolved cellular repair have been implicated as key upstream mediators of sepsis-induced organ dysfunction and death. We hypothesised that gene therapy with BRCA1, a critical regulator of DNA damage repair and cell survival, would attenuate the sequelae of sepsis and peritonitis in mice subjected to caecal ligation and perforation (CLP) and thioglycollate stimulation. C57Bl/6J mice underwent sham or CLP surgery 3 days following treatment with either human BRCA1 adenovirus (AdBRCA1) or the adeno-CMV-null vector (Adnull). The 24-h post-CLP mortality was 2.8% vs 17.9% (P<0.001) and the median post-CLP survival was 50.5 vs 33 h (P<0.05) for AdBRCA1- vs Adnull-treated mice, respectively. AdBRCA1 therapy blunted CLP-associated cardiac, pulmonary, hepatic and renal dysfunction and also reduced CLP-elicited double strand breaks and apoptosis in the liver. BRCA1 gene therapy was associated with lower CLP-evoked cardiac and hepatic superoxide generation that in the liver was in part due to improved reactive oxygen species removal. CLP also elevated mesenteric arteriolar and serum intercellular adhesion molecule-1, both of which were partially abrogated with AdBRCA1 administration. Thioglycollate-challenged AdBRCA1-treated mice displayed reduced peritoneal neutrophil recruitment and dampened cytokine elaboration relative to their Adnull-treated counterparts. Taken together, we report a novel role of BRCA1 gene therapy in limiting systemic inflammation, multiple-organ failure and mortality in experimental sepsis.

Characterization of non-linear behaviour of an animal membrane using electro-kinetic studies.

Electro-kinetic studies of water, aqueous solutions of urea, thiourea, glucose, creatinine and urine solution across urinary bladder membranes of goat have been used to explain non-linear behaviour. It has been found that fluxes are non-linearly related with forces. The structure of the membrane is a decisive factor when the range of driving forces is not too high. Stability of the steady state has also been examined and has been found to remain quite stable even in non-linear regions. The results have been examined using the methodology of non-equilibrium thermodynamics.

Primary sternal osteomyelitis.

Primary sternal osteomyelitis is a rare condition. Most of the recent cases have been reported in intravenous drug abusers. A case of primary sternal osteomyelitis with no apparent risk factors is reported. Diagnosing sternal osteomyelitis can be difficult, but failure to clinically recognize this type of infection in its early stages can lead to serious sequelae. The diagnosis should be suspected in a young patient presenting with acute inflammatory swelling over the sternum. It is further supported by leukocytosis, elevated sedimentation rate, lateral radiograph of the sternum, and positive Gram's stain. While bacteriological culture results are pending, antibiotic therapy with Staphylococcus aureus coverage should be initiated empirically. Diagnostic evaluation and management of the patients with this entity are briefly discussed.

Acute ischemia of the hand following intra-arterial oxymetazoline injection.

Acute ischemia of the hand following intra-arterial injection of a drug is an infrequent problem, but it requires urgent medical attention. In this report, a patient injected a nasal decongestant, oxymetazoline hydrochloride (Afrin), into his radial artery. This resulted in severe burning pain, and cyanotic, cold, and pulseless hand, suggestive of acute ischemia. Intra-arterial papaverine, nifedipine, anticoagulation with heparin, prednisone, and stellate ganglion block did not improve the hand circulation. Development of gangrene necessitated a disarticulation at the wrist joint. Diagnosis, complications, and therapeutic measures of acute hand ischemia secondary to intra-arterial drug injection are discussed.

Electrokinetic energy conversion studies of aqueous solutions of oxalic acid and urea across urinary bladder membranes.

Electrokinetic studies namely hydrodynamic permeability, electroosmotic permeability and streaming potential measurements of aqueous solutions of oxalic acid and urea have been made across urinary bladder membranes of goat. Energy conversion maxima and degree of coupling for these permeants have computed. It has been found that these values increase with increases in concentration of the permeants. Since electro-osmotic flux tendency is quite opposite for oxalic acid in comparison to that of urea, energy conversion values increase with increase in concentration but in opposite directions. Such studies are expected to be of use in understanding electrophysiology of the bladder as inefficient functioning of the bladder leads to formation of urinary calculi and many other types of disorders. Methodology of non-equilibrium thermodynamics have been used to explain the data.

Electrokinetic energy conversion studies of aqueous solution of urea, glucose and their mixtures across urinary bladder membranes.

Electrokinetic studies of aqueous solutions of urea, glucose, urea-glucose mixture (urea concentration increasing and glucose fixed) and glucose-urea mixture (glucose concentration increasing and urea concentration fixed) have been carried out across urinary bladder membranes of goat. Results have been analysed using methodology of non-equilibrium thermodynamics. It has been found that energy conversion maxima and degree of coupling for mixtures is higher than urea and glucose solutions. It has also been found that in the case of urea-glucose mixtures, the value of maxima and degree of coupling first decreases and then increases with increase in concentration while in the case of glucose-urea mixture, the trend is not definite. With urea solutions only, both these values increase with increase in concentration. It has been observed that energy conversion maxima and degree of coupling for urine is much higher as compared to other permeants. It appears that second order phenomenological coefficient L112 is related with degree of coupling (qe) as the trend of two is quite similar.

Electrokinetic energy conversion by aqueous oxalic acid, citric acid, ascorbic acid, hippuric acid, and acetyl salicylic acid across urinary bladder membranes.

Efficiency of energy conversion for electro-osmosis and streaming potential and the degree of coupling of acids across urinary bladder membranes of goat have been computed using non-equilibrium thermodynamic theory. The energy conversion maxima and degree of coupling for acids responsible for the formation of urinary calculi are found to be much low as compared to urea and urine.

Studies on interfacial potentials and currents of urine-urea systems across urinary bladder membrane.

Interfacial potential of urine-urea mixture across urinary bladder membranes of goat has been studied by comparing membrane-solution resistance and current data. It has been found that interfacial potential of urine solution is higher as compared to urea solution and that of urine-urea system increases with increase in concentration of urea in urine. Current generated in the system decreases with decrease in concentration of urea in the urine. Implications of electro-physiological studies in understanding the micturition process are discussed.

Ocular burn from microwaved egg.

Ocular thermal injuries from improper use of a microwave oven are rare. Manufacturers recommend cooking eggs in the microwave only after the shell has been removed and the yolk sac has been pierced with a pin. Failure to follow these instructions is likely to result in ocular and facial burns. Only eight adult cases of such injuries have been documented so far. Ocular burn from the explosion of a microwaved egg in a pediatric patient is being reported for the first time in the English medical literature.

Plantar cellulitis.

An unusual case of acute cellulitis of the foot in a child is reported. The child failed to respond to standard treatment even after removal of an occult foreign body. Wound cultures revealed Klebsiella oxytoca and Citrobacter freundii. This is the first documented report on Klebsiella oxytoca in cellulitis. The cellulitis resolved after being treated with the appropriate antibiotics.

Electrokinetic studies of urine-urea mixture across bladder membranes.

PURPOSE: We ascertain the role of urea in urine and its probable effects on the polarizable behavior of bladder interfaces. MATERIALS AND METHODS: Urine was systematically diluted, keeping overall volume the same. The methodology of nonequilibrium thermodynamics was used, which involves measurements of hydrodynamic permeability, electro-osmotic permeability, streaming potential and streaming currents, respectively. RESULTS: Effective pressure terms (alpha 1) and polarizability terms (alpha 2) were computed, making use of higher order phenomenological coefficients, and their concentration dependence was examined. Abrupt changes in the values of alpha 1 and alpha 2 are supported by trends in higher order phenomenological coefficients. CONCLUSIONS: The polarizable behavior of the bladder is maintained up to certain concentrations of urea in urine and then it undergoes drastic changes. The role of the bladder in situations of improper functioning of the liver and diets without protein may provide an explanation.

Diagnosis of thoracic outlet syndrome in the emergency department.

The use of the emergency department (ED) as a source for primary care has increased the number of patients seen in this setting with even chronic symptoms such as pain, paresthesias, and weakness in the upper extremity. This group may include individuals with thoracic outlet syndrome (TOS). We were concerned that TOS may be underdiagnosed in the ED because of physician unfamiliarity with the signs and symptoms of TOS. Hence, we retrospectively studied cases of TOS seen at the ED of the University hospital during a 29-year period. We believe this is the first report in the English language literature to reflect the assessment and management of TOS in the ED. The study data include clinical presentation, diagnostic tests, and management of TOS. Lack of thorough evaluation resulted in underdiagnosis of TOS in our ED. We recommend that ED personnel pay close attention to patients with symptoms of long duration and that ED physicians be aware of TOS presentation and its management.

Simultaneous asymmetric bilateral traumatic hip dislocation.

A 25-year-old man presented to the emergency department with simultaneous right anterior and left posterior hip dislocations resulting from a motor vehicle accident. Simultaneous bilateral traumatic hip dislocation is an uncommon occurrence. More rare is asymmetric simultaneous bilateral hip dislocation, with only ten cases documented in the English-language literature. The importance of an anteroposterior pelvic radiograph after significant major trauma is emphasized. Several serious complications can be associated with this condition, so expeditious management in the ED is warranted.