Absolute configuration of (+)-[fluoro(hydroxyphenylphosphinyl)methyl]-phosphonic acid, a specific inhibitor of Na(+)-gradient-dependent Na(+)-phosphate cotransport across renal brush border membrane, by X-ray crystallographic analysis of its (-)-quinine salt.

Racemic [fluoro(hydroxyphenylphosphinyl)methyl]phosphonic acid (1) and its individual enantiomers [(+), 98% ee; (-), 67% ee] were previously shown to inhibit Na(+)-gradient-dependent Na(+)-phosphate cotransport across renal brush border membrane, without measurable stereospecificity. Resolution of 1 was effected by fractional recrystallization of its (-)-quinine salts. The more levorotatory, diquinine product 2, corresponding to (+)-1, has now been analyzed by X-ray crystallography and found to be composed of the S enantiomer of 1. This result confirms the absence of stereochemical preference in inhibition of the cotransporter by the enantiomers of 1 and provides the first absolute configuration assignment of an asymmetrical alpha-halomethylene pyrophosphate analogue.

"Half and half" woven and knitted Dacron grafts in the aortoiliac and aortofemoral positions: seven and one-half years follow-up.

One-hundred fifty-eight patients received specially manufactured aortoiliac or aortofemoral bifurcated grafts with one limb woven, the other knitted from Dacron. During an observation period ranging from 1,567 to 2,555 days (average 2,130 days) no statistically significant difference was found in either platelet adherence (30 patients studied) or in clinical patency. According to the results of the study, the type of graft (woven or knitted) did not seem to influence either platelet adherence or patency rate in the aortoiliac or aortofemoral positions.

Prevention of retrovirus infection after injury with contaminated instruments: an experimental study.

Owing to similarities between human immunodeficiency virus and feline retroviruses, the feline model was chosen for the study to investigate the efficacy of timely topical treatment of accidental human immunodeficiency virus infection in the operating room. Cats were subcutaneously inoculated with either feline leukemia virus or feline immunodeficiency virus. An effort was made to neutralize the virus in loco either by infiltration of the inoculation site with povidone-iodine or with monoclonal antibodies, or by cauterization and excision. The animals were periodically monitored for feline leukemia virus antigens or for feline immunodeficiency virus antibodies. The results indicated that in the feline model, the development of generalized virus infection may be prevented by local measures if applied immediately.

Can AIDS be prevented after injury with contaminated instruments?

Particulate matter comparable in size with that of human immunodeficiency virus was subcutaneously injected into experimental animals. Such matter remained at the inoculation site long enough to suggest the possibility that human immunodeficiency virus can be destroyed in loco before it invades the host's circulation. These findings may be useful in developing a method to prevent acquired immunodeficiency syndrome after accidental injury with human immunodeficiency virus-contaminated instruments.

Biological thresholds of cold-induced phrenic nerve injury.

The effects of controlled cooling on phrenic nerve signal conduction were investigated by cooling an isolated segment of the phrenic nerve with a constant but variable temperature probe. The conduction of a standard electrical stimulus applied to the nerve proximal to the cooled section was measured by detector electrodes sutured to the diaphragm. Nerve conduction of the applied stimulus ceased between 10 degrees and 12 degrees C but returned within seconds after the probe was removed. The delay in the return of conduction increased as nerve temperature decreased until at a temperature of 4 degrees C the ability to conduct did not return after 4 hours. The amount of fat surrounding the nerve and the blood flow rate along the cooled portion of the nerve were observed to ameliorate the effects of low temperature on stimulus conduction. Total body cooling also appears to offer some protection against loss of conduction.

Experiments with a bowl of saline: the hidden risk of hypothermic-osmotic damage during topical cardiac cooling.

Some of the misconceptions in the application of cardiac hypothermia are that the temperature of cold normal saline solution is necessarily above 0 degrees C, cold saline solution and slush are relatively safe for living tissues, and normal saline will retain normal osmolality even if partially frozen. These postulates were examined in thermodynamic experiments that demonstrated three points: (1) The temperature of unfrozen saline solution may drop way below the freezing point. (2) When liquids and solid components of saline solution are separated, the components will become hypo-osmolar or hyperosmolar. (3) Ice chips and slush ice produced in the operating rooms may reach temperatures as low as -36 degrees C. We recommend that the possibility of these events should be taken into consideration whenever topical cardiac hypothermia is clinically applied.

Presence of antibodies to the polymerase gene product(s) of hepatitis B and woodchuck hepatitis virus in natural and experimental infections.

Antibodies against synthetic peptides derived from the polymerase gene of the hepatitis B virus (HBV) were present in 80% of renal dialysis patients infected with HBV and in woodchucks infected with woodchuck hepatitis virus (WHV). Polymerase antibody (anti-pol) appeared as the earliest marker of both HBV and WHV infections in approximately half of the individuals tested, suggesting that these antibodies were generated following early viral replication in the liver during the incubation period and prior to the appearance of virus in the blood. Many HBV- or WHV-infected individuals negative for surface antigen throughout infection also had anti-pol, but anti-pol appeared only after anti-surface, anti-core and/or anti-e. The presence of anti-pol did not correlate with other serologic markers of HBV or WHV infection, nor did it correlate with histologically confirmed hepatitis in woodchucks. However, there was a significant correlation between the presence of anti-pol and elevated liver enzyme levels in the sera of renal dialysis patients. In several cases, anti-pol was the sole marker of infection, suggesting that underlying infection and low levels of virus replication were present. Most individuals with anti-pol had antibodies to one of the three synthetic peptides, suggesting it may be immunodominant in natural infections. In human populations, groups with a high frequency of HBV infection have a high frequency of polymerase antibodies, and groups with a low frequency of HBV infection have a low frequency of polymerase antibodies. A standard assay for the detection of polymerase antibodies is described, and possible clinical applications are discussed.

Retrograde air embolization in coronary operations.

Observations during coronary operations are presented that prove that if the ascending aorta is cross-clamped and suction applied to the left side of the heart or to the aortic root for venting purposes, the pressure rapidly drops in the coronary arterial system and a situation is created in which air may enter through the coronary arteriotomy and pass into the aortic root and the left ventricle. Another mechanism to explain the occurrence of some cases of "iatrogenic" air embolism has also been presented: introduction of air into the ascending aorta while cardioplegic solution is being injected through peripherally attached bypass grafts. Air trapped in these grafts or in the coronary artery itself may propagate proximally as well as distally in the coronary arteries and may reach the aortic root even if the left side of the heart is left unvented. These mechanisms may be responsible for heretofore unexplained cases of "iatrogenic" air embolization. We recommend careful purging of air, which may be present, from the left ventricle and aortic root every time before the aortic cross-clamp is removed during coronary operations.

Indium 111-labeled platelet deposition in woven and knitted Dacron bifurcated aortic grafts with the same patient as a clinical model.

A study was designed to compare platelet deposition between knitted and woven Dacron grafts in the same patient. Twenty patients received aortoiliac or aortofemoral bifurcated Dacron grafts, each composed of one woven and one double-velour knitted limb. External nuclear graft imaging was carried out after injection of autologous platelets labeled with indium 111. The patients were studied postoperatively in time periods ranging from 6 days to 42 months. Platelet accumulation was almost identical in knitted and woven limbs in all patients. This study appears to indicate that there is no difference in thrombogenicity between knitted and woven bifurcated Dacron grafts in the aortoiliac or aortofemoral positions measured by platelet accumulation.

In vitro effect of a microfibrillar collagen hemostat on platelets.

Microscopic particles of microfibrillar collagen hemostat (MCH) have been shown to pass through a 40-micron blood transfusion filter. This study indicates that MCH passing through the filter retains a significant portion of its ability to aggregate platelets in vitro and the aggregating ability is dose related. The extent of platelet aggregation in the presence of the MCH filtrate or an ADP standard was measured photometrically and log dose-response curves constructed from the data. An ED50 of 3.6 micrograms protein/ml platelet-rich plasma (PRP) was calculated at a protein concentration of 7.6 mg/ml in the MCH filtrate and an ED50 of 5.9 micrograms protein/ml PRP at 12 mg/ml protein in the MCH filtrate. The platelet aggregating ability of the MCH filtrates corresponded to 18.8 and 39.6% of the maximum response produced by adenosine-5'-diphosphate. These findings support the view that blood contaminated with MCH should not be returned to a patient's circulation.

Inherent dangers of simultaneous application of microfibrillar collagen hemostat and blood-saving devices.

Microfibrillar collagen hemostat is a topically applicable hemostatic agent that has been introduced relatively recently. Because of the possibility that this substance may pass through different blood-collecting circuits and cause organ damage if reintroduced into the patient's circulation, we performed a series of in vitro and in vivo experiments. The results of these experiments suggest that such a passage may indeed occur and could cause organ damage, either by direct or by induced embolization that cannot be completely prevented even with the application of commercially used filters. We therefore recommend that the substance should not be used if the shed blood is intended to be collected and returned into the patient's circulation.

An autoperfused heart-lung-preparation: metabolism and function.

The number of heart transplantations performed in the United States is increasing, and better preservation techniques are needed for distant transport and improved organ viability. Earlier experiments demonstrated that the autoperfused heart-lung preparation maintains adequate function for six to seven hours without exogenous substrates or medications. The present study evaluated the metabolic alterations at normothermia in an autoperfused heart-lung preparation and if its longevity can be extended by satisfying metabolic requirements. Thirty autoperfused heart-lung preservations were tested with an elevated buffer-bag that maintained left ventricle pressure between 75 mm Hg and 80 mm Hg. The entry and exit ports of the buffer-bag were fitted with one-way valves to insure blood circulation. Left ventricle and arterial pressure, blood pH, PCO2, PO2, glucose, free fatty acids, pyruvate and lactate were measured at regular intervals. In a first series of experiments, myocardial biopsies were taken for ATP determinations. The autoperfused heart-lung preparations were found to consume preferentially free fatty acids until their arterial level dropped to 350 +/- 24 microEq/L. Glucose then became the perferred substrate. After six to seven hours, when the glucose level dropped to 10 mg/dL, the cardiac activity stopped. In a second series, a 10% glucose solution containing 25 IU/dL of insulin was infused at a rate of 0.1 mL/min, extending the longevity of the preparation up to 18 hours. Then, the heart dilated and abruptly stopped. Massive bacterial contamination was found. When aseptic techniques were used in conjunction with antibiotics, the longevity was extended to 24 hours.(ABSTRACT TRUNCATED AT 250 WORDS)