Cerebral blood flow and metabolism in chronically hyperammonemic rats: effect of an acute ammonia challenge.

The effects of chronic hyperammonemia on cerebral metabolism were studied in rats four and eight weeks after the construction of a portacaval shunt. Compared to sham-operated controls, shunted animals had increased arterial concentrations of ammonia and glutamine and decreased glutamate. Cerebral blood flow, measured by xenon 133 washout in animals lightly anesthetized with nitrous oxide, increased from a control of 91 +/- 5 (mean +/- SEM) to 139 +/- 20 ml per 100 gm tissue per minute after shunting for eight weeks; however, the cerebral metabolic rate for oxygen was not different from control four or eight weeks after the shunting procedure. Following intraperitoneal administration of a small ammonium acetate load (2.6 mmol/kg), eight-week portacaval animals consistently underwent a fall in cerebral blood flow and cerebral oxygen consumption and developed high-voltage slow waves in the electroencephalogram. Glutamine was produced by the brains of all groups of animals; the cerebral metabolic rate for glutamine was greater than control in eight-week portacaval rats, the only animals to show a net uptake of ammonia into brain. The findings suggest that increased cerebral sensitivity to ammonia, along with nonspecific effects of chronic portal-systemic shunting, may lead to uncoupling of cerebral blood flow and oxidative metabolism.


Chronic ketosis and cerebral metabolism.

The effects of chronic ketosis on cerebral metabolism were determined in adult rats maintained on a high-fat diet for approximately three weeks and compared to a control group of animals. The fat-fed rats had statistically significantly lower blood glucose concentrations and higher blood beta-hydroxybutyrate and acetoacetate concentrations; higher brain concentrations of bound glucose, glucose 6-phosphate, pyruvate, lactate, beta-hydroxybutyrate, citrate, alpha-ketoglutarate, alanine, and adenosine triphosphate (ATP); lower brain concentrations of fructose 1,6-diphosphate, aspartate, adenosine diphosphate (ADP), creatine, cyclic nucleotides, succinyl coenzyme A (CoA), acid-insoluble CoA, and total CoA; and similar brain concentrations of glucose, malate, calculated oxaloacetate, glutamate, glutamine, adenosine monophosphate, phosphocreatine, reduced CoA, acetyl CoA, sodium, potassium, chloride, and water content. The metabolite data in the chronically ketotic rats demonstrate an increase in the cerebral energy reserve and energy charge. These data also suggest negative modification of the enzymes phosphofructokinase, pyruvic dehydrogenase, and alpha-ketoglutaric dehydrogenase; positive modification of glycogen synthase; and possible augmentation of the hexose transport system. There was no demonstrable difference in brain pH, water content, or electrolytes in the two groups of animals. We speculate that the increased brain ATP/ADP ratio is central to most, if not all, the observed metabolic perturbations and may account for the increased neuronal stability that accompanies chronic ketosis.


Intracranial arteriovenous malformations in childhood.

During the 13-year period 1964 through 1976, 37 patients less than 20 years with an intracranial, parenchymal arteriovenous fistula were seen at the Mayo Clinic. The most frequent mode of presentation was hemorrhage or seizure. Other than angiography, computed tomography with contrast enhancement was the most helpful diagnostic test. Surgery was restricted to patients with intraparenchymal hematomas, intractable seizures, or subarachnoid hemorrhage with accessible lesions and to 1 infant with a massive, sumptomatic malformation. Surgery generally  was tolerated well, with reversal of most acute focal neurological deficits related to hematomas. In the nonsurgical group, follow-up revealed a fairly stable neurological status during the period of the study.


Proximal versus distal slowing of motor nerve conduction velocity in the Guillain-Barré syndrome.

Using the F wave, a simple equation was devised to calculate the ratio between motor nerve conduction time from the spinal cord to the stimulus site and that of the remaining nerve segment to the muscle (F ratio). In 33 healthy subjects the F ratio (mean +/- SD) was close to unity for the median nerve (1.04 +/- 0.09) with stimulation at the elbow and for the peroneal (1.11 +/- 0.09) and tibial nerves (1.17 +/- 0.10) with stimulation at the knee. Thus, in these nerves, the time required for the passage of impulses from the cord to the site of stimulation is approximately the same as that from the stimulus site to the muscle. The ratio was significantly more for the ulnar nerve (1.40 +/- 0.11) with stimulation below the elbow. Of 126 nerves in the upper and lower extremities from 45 patients with Guillain-Barré syndrome, the F ratio was normal in 65 (51%), increased in 30 (24%), and decreased in 31 (25%). The mean F ratios remained normal in median (1.12 +/- 0.40), ulnar (1.38 +/- 0.30), peroneal (1.07 +/- 0.25), and tibial (1.12 +/- 0.20) nerves. These findings together with the results of nerve conduction studies indicate that the conduction abnormality usually affects both  proximal and distal segments in the Guillain-Barré syndrome. If selective, it is distributed at random between the two segments, but there is a tendency toward involvement of common sites of compression and the most proximal, possibly radicular, portion of the nerve.


Effect of prednisolone on motor end-plate fine structure: a morphometric study in hamsters.

The fine structure of quadriceps motor end-plates in hamsters was analyzed quantitatively one, two, four, seven, and thirty-two weeks following intraperitoneal injections of prednisolone. Except for transient increases in postsynaptic length and membrane profile concentration after prednisolone administration at dosages of 4 mgper kilogram of body weight for one week and 2 mg per kilogram for four weeks, mean values for various measurable profiles in the presynaptic and postsynaptic regions showed no significant differences between control and treated animals.


Benign cerebellar hemorrhages.

Two patients with cerebellar hemorrhage and a benign outcome stress the potential for spontaneous resolution and clinical recovery in some cases of this disorder. In each patient, resolution of the hemorrhage was noted on the computed tomographic scan. Computed tomography may detect a cerebellar hemorrhage even though on clinical grounds a brainstem localization is favored.


Effects of hypothermia on the human brainstem auditory response.

Latency measurements between three potentials (waves I, III, and IV/V) of the human brainstem auditory response can allow early detection of certain posterior fossa lesions. The diagnostic use of these interwave latencies requires knowledge of what factors may prolong them in the absence of disease. Hypothermia appears to be one such factor--in 5 neurologically and audiometrically normal patients, mean esophageal temperatures as high as 34.5 degrees C resulted in prolongations of central auditory conduction time. Interwave latency prolongations that were abnormal relative to an age-matched normal population were seen at 32.1 degrees +/- 0.3 degrees C in patients with both spontaneous and induced hypothermia, and these abnormalities disappeared after rewarming to normothermia. Hypothermia often accompanies intoxication and coma and should therefore be considered when brainstem auditory response abnormalities are being interpreted in these two clinical conditions.


Charge movement in the membrane of striated muscle.

This account of charge movement in striated muscle membrane must be regarded as essentially tentative. I have tried to present, within a simplified descriptive scheme, one way in which the present confusion of results can be resolved into a self-consistent account. But I am sure that as more complete and more accurate measurements are made, the deficiencies of this account will become even clearer. Nevertheless I believe that any successful description of the dielectric properties of biological membranes will have to take account of slow and nonlinear polarization of numerous membrane constituents and of the improbability of finding within the experimentally available range any finite potential region where polarization is linear.


Cefaclor: in vitro spectrum of activity and beta-lactamase stability.

The in vitro activity of cefaclor against 556 clinical isolates of gram-positive and gram-negative bacteria was compared with that of other cephalosporins. Cefaclor had activity similar to that of cephalexin against gram-positive bacteria. It showed greater activity against Haemophilus strains than did cephalexin and inhibited beta-lactamase-producing Haemophilus isolates. Cefaclor was more active than cephalexin or cephalothin against Escherichia coli, Salmonella, and Shigella isolates but did not act against Serratia, Acinetobacter, indole-positive Proteus, or Bacteroides isolates. Cefaclor was resistant to type III (TEM) beta-lactamases but was destroyed by type I beta-lactamases and, to a lesser degree, by type IV and type V beta-lactamases.


Cetocycline, tetracycline analog: in vitro studies of antimicrobial activity, serum binding, lipid solubility, and uptake by bacteria.

Cetocycline (formerly chelocardin or cetotetrine) is structurally related to the tetracyclines. It was found to be more active than tetracycline against many clinical isolates of aerobic gram-negative bacilli, but is less active against staphylococci, and has no activity against Pseudomonas. It is bactericidal against susceptible enteric gram-negative bacteria at concentrations two to four times higher than the minimal inhibiting concentrations. The drug is highly lipid soluble; more than 80% is bound to serum, and it is more avidly taken up by susceptible bacteria than tetracycline. A direct correlation between drug uptake and susceptibility of bacteria was not noted, except with a strain of Proteus vulgaris.


Aminoglycoside modification by gentamicin-resistant isolates of Staphylococcus aureus.

Three clinical isolates of Staphylococcus aureus, which were previously shown to contain a 50S plasmid conferring resistance to several aminoglycosides, were examined for modifying enzymes. Both the wild-type and heat-cured derivatives of the isolates were screened for acetyl-, adenylyl-, and phosphotransferase activities. The substrates were gentamicin, amikacin, and netilmicin; the results indicated that even though all three activites were present, the phosphotransferase reaction was most responsible for resistance to these antibiotics. The absence of any of the modifying activites in cured derivatives of the three isolates supports the conclusion that aminoglycoside resistance in these strains is conferred by a plasmid.


Accumulation pharmacokinetics of tobramycin.

Tobramycin pharmacokinetics is usually described by a one-compartment model, but this model fails to account for both the incomplete urinary recovery and prolonged post-treatment persistence noted with this drug. We examined the multiple-dose behavior of tobramycin in 35 treated patients with stable renal function, using peak and trough serum concentrations, urine recovery, and postmortem tissue analysis. Serum concentrations rose slowly throughout treatment and declined in two phases after the drug was stopped. The first-phase half-life correlated well with renal function, but the second averaged 146 h and was poorly related to creatinine clearance. A two-compartment model was used to describe the biphasic decline in serum concentrations and to calculate the amount of drug in the tissue compartment at all times during and after treatment. Predicted tissue amounts rose continually throughout treatment in all study patients. In 5 patients, the total amount of tobramycin in the body after the final dose was recovered in the urine, but urine had to be collected for 10 to 20 days to achieve complete recovery of the drug. In four patients, the predicted tissue amount was recovered from postmortem tissues. Regardless of the dose, tobramycin accumulated in the tissues of all patients receiving this antibiotic. The two-compartment pharmacokinetic model explains both the rising peak and trough concentrations during treatment and the detection of the drug in serum and urine long after the last dose.


Medium-dependent variation in bactericidal activity of antibiotics against susceptible Staphylococcus aureus.

Staphylococcus aureus resistant to bactericidal activity of antibiotics caused sepsis in three patients. Bacteriological and clinical responses were not achieved until serum and tissue fluid levels of administered antibiotics exceeded the minimum bactericidal concentration (MBC) of the infecting organism. Fifteen clinical isolates of S. aureus were tested in brain heart infusion broth and Mueller-Hinton broth for the MBC of gentamicin, vancomycin, clindamycin, oxacillin, cefazolin, and cephalothin. Results showed significant eightfold or greater broth-dependent differences in the MBC of at least one antibiotic against 87% (13/15) of strains tested. The MBC was unpredictable and varied with the strain, antibiotic, and medium used. No controlled studies are available to indicate the clinical significance of the MBC demonstrated in different media. The necessity for treating serious infection with bactericidal drugs has not yet been established; however, in septicemia such as that caused by bacterial endocarditis, bacteriostatic antibiotics have generally failed to eradicate the infection, whereas bactericidal agents have often been curative. Therefore, in patients unresponsive to usual antistaphylococcal therapy, we suggest that MBC testing be performed in at least two media and that treatment be instituted with antibiotics demonstrating the lowest MBC in all media used.


New plasmid (pTU512), mediating resistance to penicillin, erythromycin, and kanamycin, from clinical isolates of Staphylococcus aureus.

Multiply drug-resistant strains of Staphylococcus aureus were isolated from pediatric patients with severe staphylococcal infections in 1974 through 1976. Resistance to benzylpenicillin, erythromycin, and kanamycin was jointly eliminated without exception from these multiply drug-resistant strains by treatment with ethidium bromide. It was also found that the triple drug resistance in a representative strain, TK512-200, was always transduced to a susceptible strain simultaneously. Moreover, a single class of plasmid deoxyribonucleic acid was isolated from a transductant and found to be 14.4 +/- 0.6 mum in length, with a molecular weight corresponding to 29.8 x 10(6). From these results, it is concluded that the plasmid (pTU512) is a new one, mediating resistance to penicillin, erythromycin, and kanamycin.


Fungal toxicity of phosfon D and its reversion by lipids.

The growth retardant Phosfon D inhibits the growth of some yeasts and human pathogenic filamentous fungi. The toxic effects of the compound on the dermatophyte Microsporum cookei were completely reversed by adding ergosterol and oleic acid to the medium. The significance of these findings is discussed.


Synergism of fosfomycin-ampicillin and fosfomycin-chloramphenicol against Salmonella and Shigella.

Ninety strains of Salmonella and 50 strains of Shigella were tested for susceptibility to fosfomycin, chloramphenicol, and ampicillin by the agar dilution method. Drug interaction between fosfomycin-ampicillin and fosfomycin-chloramphenicol was studied by the agar dilution method. The fractional inhibitory concentration was calculated. The combination of fosfomycin-ampicillin was synergistic against Salmonella in 74 cases, additive in 7, indifferent in 7, antagonistic in none, and nonevaluable in 2; against Shigella it was synergistic in 27 cases, additive in 9, indifferent in 14, and antagonistic in none. The combination of fosfomycin-chloramphenicol was synergistic against Salmonella in 56 cases, additive in 9, indifferent in 13, nonevaluable in 12, and antagonistic in none; against Shigella it was synergistic in 29 cases, additive in 10, indifferent in 9, nonevaluable in 2, and antagonistic in none. Killing curves with combinations of each antimicrobial agent showed that the cultures that had proven to be indifferent by the agar dilution method showed a bactericidal effect until h 4, with posterior regrowth of the culture after this time period. For the strains in which synergism was demonstrated, total bactericidal activity was reached at 24 h.


Trypanocidal activity of antitumor antibiotics and other metabolic inhibitors.

A microtest has been devised for the rapid preliminary assay in vitro of the effect of over 100 drugs and inhibitors on African trypanosomes (Trypanosoma brucei and T. rhodesiense). Parasite motility and infectivity for mice are indexes, respectively, of respiration and glycolysis and of cell division; trypanocidal titers based on these indexes can show primary metabolic areas of drug attack. Various specific inhibitors have also been tested to detect metabolic sites which might be therapeutically vulnerable. RNA synthesis inhibitors are highly active (adenine nucleosides, daunorubicin, doxorubicin, chromomycin, actinomycin D, mitomycin C); the activity of the nucleoside cordycepin was increased in vitro and in vivo by an adenosine deaminase inhibitor. In view of the polyanionic nature of the trypanocide suramin, a series of polyanions was tested; several showed activity but only poly-d-glutamic acid was active in vivo. Among various miscellaneous inhibitors, quercetin, disulfiram, and the Ca-complexing agents arsenazo I and III showed marked activity, the latter exclusively on the arsenical-resistant T. brucei. The implications of these results for combination chemotherapy and depot prophylaxis (with polyanions) are indicated.


Clinico-pharmacological studies of sisomicin in ill children.

Sisomicin, at 4.5 mg/kg per day, was prescribed for the therapy of serious bacterial infections of hospitalized infants, children, and adolescents. Eleven children received full treatment courses, with 10 clinical and 9 bacteriological cures. Three patients with underlying disease (two cystic fibrosis and one aplastic anemia) accounted for the failures. Mean half-life was 98.3 min (range, 26.1 to 159.3), and peak serum concentrations 10 min after intravenous infusion were similar (5 to 6 mug/ml) on days 1, 3, and 5 of therapy. Mean urinary concentrations were 54.3 mug/ml; 31 to 47% of the drug was excreted within the 8-h dosage interval. The drug was tolerated well by all patients; however, one patient, receiving the longest duration of therapy (26 days), developed reversible nephrotoxicity.


In vitro activity of rifampin alone and in combination with nafcillin and Vancomycin against pathogenic strains of Staphylococcus aureus.

Twenty strains of Staphylococcus aureus isolated from patients with endocarditis were examined in vitro for susceptibility to rifampin, nafcillin, and vancomycin and to combinations of rifampin with nafcillin or vancomycin. Minimum bactericidal concentrations of rifampin ranged from 0.0031 to 0.0125 mug/ml, of nafcillin ranged from 0.078 to 0.312 mug/ml, and of vancomycin ranged from 0.312 to 1.25 mug/ml. The combination of rifampin with nafcillin was synergistic for 12 strains; the combination of rifampin plus vancomycin was synergistic for 5 of the isolates.


In vitro and in vivo studies of ambruticin (W7783): new class of antifungal antibiotics.

Ambruticin is a cyclopropyl-pyran acid, representing a new class of antibiotics. It has a relatively broad antifungal spectrum in vitro and is highly active against dimorphic as well as filamentous organisms. Of 24 strains of dermatophytic fungi tested, the majority were susceptible to ambruticin at 0.049 mug/ml or less. The minimal inhibitory concentration for the systemic fungi Histoplasma capsulatum and Blastomyces dermatitidis was 0.049 to 0.39 mug/ml. Ambruticin is fungicidal for metabolizing cells of Microsporum fulvum and does not cause cell leakage of 260-nm absorbing material. The antibiotic is effective orally as well as topically in guinea pigs experimentally infected with Trichophyton mentagrophytes. In mice, a single oral dose of 75 mg/kg produced peak serum levels of 45 mug/ml in 1 h with a serum half-life of 3.1 h. Excretion of the antibiotic is principally by the biliary route.


Synergy of azlocillin and mezlocillin combined with aminoglycoside antibiotics and cephalosporins.

Synergistic activity between both azlocillin and mezlocillin and aminoglycosides or cefazolin could be demonstrated by checkerboard dilution, isobologram, and killing curve techniques. Azlocillin and mezlocillin combined with gentamicin, netilmicin, or amikacin were synergistic against Escherichia coli, Klebsiella, Citrobacter, Enterobacter, Serratia, and indole-positive Proteus. Synergy was observed with isolates that were susceptible or resistant to azlocillin or mezlocillin. Synergy was seen most often when azlocillin or mezlocillin were combined with amikacin, gentamicin, or netilmicin against Pseudomonas aeruginosa. The combination of mezlocillin and an aminoglycoside produced synergy more often than did carbenicillin plus an aminoglycoside. No antagonism was seen when aminoglycoside antibiotics were combined with azlocillin or mezlocillin. Cefazolin was synergistic against Pseudomonas, Providencia, P. mirabilis, indole-positive Proteus, Citrobacter, Klebsiella, and Escherichia coli, when combined with azlocillin or mezlocillin. However, the combination of either agent with cefazolin was antagonistic when tested against selected indole-positive Proteus and Enterobacter isolates.


Pharmacology and efficacy of netilmicin.

Twenty-six patients, 20 to 77 years of age, were treated with netilmicin, mean dose 2 mg/kg every 8 h intramuscularly or in a 20-min intravenous infusion. The mean serum half-lives in patients with creatinine clearances of >/=90 ml/min and 60 to 90 ml/min were 3.2 and 3.4 h, respectively. In patients with serum creatinines of </=1.4 mg/100 ml and creatinine clearances of >/=60 ml/min, mean serum levels were 9.0 and 1.2 mug/ml, respectively, 5 to 15 min and 7.5 h post-intravenous infusion, and 7.1 and 1.7 mug/ml, respectively, 1 and 8 h post-intramuscular injection. Twenty-five patients had acute pyelonephritis; 7 of the 25 had bacteremia. The infecting bacteria were Escherichia coli (15), Proteus mirabilis (5), Pseudomonas aeruginosa (2), Klebsiella pneumoniae (1), Enterobacter hafniae (1), and both Proteus rettgeri and Proteus morganii (1). All were inhibited by 6.3 mug of netilmicin per ml, except for the P. rettgeri, which required 25 mug/ml for inhibition. Of 23 patients who could be evaluated, 19 were bacteriologically and clinically cured at follow-up. Of the remaining four, one relapsed, two became reinfected, and one was lost to follow-up. Five patients developed nephrotoxicity; two of the five had previous renal insufficiency. Three patients, one with abnormal renal function, developed ototoxicity detected only with audiograms. These studies suggest that netilmicin is effective in serious gram-negative bacillary infections, but is nephrotoxic and ototoxic in humans.


Evaluation of a dispensing instrument (Dynatech MIC-2000) for preparing microtiter antibiotic plates and testing their potency during storage.

The MIC-2000 96-channel dispenser was evaluated for accuracy and repeatability of dispensing 50-mul volumes of water. It was found to perform within the manufacturer's specifications for accuracy of +/-5%, but not within the limits for repeatability of +/-1%. Overall, instrument performance was found to be satisfactory for the antimicrobial susceptibility testing technique which has been implemented in this laboratory. A method is suggested for simple evaluation of the volumes dispensed. A variety of antibiotics may be stored in Trypticase soy broth in Microtiter plates without loss of potency for periods of at least 2 weeks at -20 degrees C and 4 months at -70 degrees C.


Clinical pharmacology of cefadroxil in infants and children.

The pharmacokinetics of cefadroxil suspension were studied in 30 children, 13 months to 12 years of age (mean age, 5.7 years). Average peak concentrations in serum of 11 to 14 mug/ml and of 7 to 10 mug/ml after 15- and 10-mg/kg doses, respectively, were not substantially affected by the feeding status. The serum half-life values were 1.3 to 1.5 h. Cefadroxil was detected in saliva of all children 2 h after 15-mg/kg doses: the levels ranged from 0.17 to 2.6 mug/ml (mean, 0.46 mug/ml). The average concentrations in urine were 1,700 and 2,620 mug/ml at 0 to 2 and 2 to 4 h, respectively, after 15-mg/kg doses. In a randomized controlled study of 50 children with impetigo, cefadroxil was as effective as penicillin G in curing existing lesions and in preventing development of new lesions. Cefadroxil may be useful for therapy of mucocutaneous and urinary tract infections in infants and children.


Production and property of beta-lactamases in Streptomyces: comparison of the strains isolated newly and thirty years ago.

Productivity and property of beta-lactamases of Streptomyces strains isolated from soil some 30 years ago were studied in comparison with those of the newly isolated strains. At least three-quarters of the Streptomyces strains produced beta-lactamase constitutively and extracellularly, mainly as penicillinases, as in the cases of those from the newly isolated strains. Strains such as S. albus, S. diastatochromogenes, S. fradiae, and S. lavendulae were the highest producing strains, and the amounts of beta-lactamase activity they produced were comparable to those produced by Bacillus cereus 569/H and B. licheniformis 749/C. In isoelectric focusing, most strains contained one main beta-lactamase band with a number of satellite bands, but some strains contained one band only. Although beta-lactamases from most strains showed isoelectric points of pH 5 to 6, some strains produced beta-lactamases with strongly basic isoelectric points of pH 8 to 9. Molecular weights were between 20,000 and 30,000. From these results, it is suggested that the proportion of the producing strains of Streptomyces and the properties of the beta-lactamases have not been affected significantly by the introduction of penicillin into the natural environment, in contrast to the cases of other microorganisms.


Inhibition of platelet function by sulbenicillin and its metabolite.

The effect of sulbenicillin and its major metabolite, alpha-sulfobenzylpenicilloic acid, on platelet function was investigated. Sulbenicillin caused inhibition of platelet aggregation and release reaction in the same manner as carbenicillin. alpha-Sulfobenzylpenicilloic acid was found to cause much stronger inhibition of platelet function. The results indicate that the strong inhibitory action of alpha-sulfobenzylpenicilloic acid may also take part in impaired platelet functions following administration of sulbenicillin to humans.


Yersinia enterocolitica: in vitro antimicrobial susceptibility.

Using 21 antimicrobial agents, agar dilution susceptibility tests were carried out against 190 strains of Yersinia enterocolitica. Isolates from human, environmental, and animal sources had essentially equal susceptibility patterns.


In vitro evaluation of a semisynthetic derivative of gentamicin B (Sch 21420).

The activities of Sch 21420 and amikacin were compared in vitro against 448 clinical bacterial isolates and against 82 gentamicin-resistant isolates of gram-negative bacilli. At 1 mug/ml, Sch 21420 was more active than amikacin against most Enterobacteriaceae but less active against Pseudomonas aeruginosa. Activity of these antibiotics against gentamicin-resistant organisms varied according to the species examined.


Bilateral cervical posterior rhizotomy: effects on dystonia and athetosis, on respiration and other autonomic functions.

Bilateral cervical posterior rhizotomy of C1 through C4, C5 or C6 was performed in 16 patients affected by dystonia and athetosis resulting from infantile cerebral palsy. The majority showed decreased muscle spasms and athetoid movements, with some improvements in their posture and voluntary mobility. 5 patients suffered from uneven and irregular breathing associated with lethargy immediately postoperatively, and 4 also showed reduced diaphragmatic activity; all 4 of these patients developed pneumonia, transitory in 3, but fatal to the other. Urinary retention lasting for a maximum of 3 months occurred in 4 of the 5 patients. The authors suggest that the lesion of ascending reticular fibers in the cervical posterior roots could have been responsible for the observations.


Prognostic index in malignant melanoma.

A retrospective study was undertaken of 146 surgically treated subjects with primary cutaneous melanoma of which 73 were disease-free for five to nine years and 73 developed later metastases. A prognostic factor was south to determine patients with poor prognoses. The best overall method was shown to be the evaluation of the prognostic index defined as the product of tumor thickness and the number of mitoses per square millimeter. However, for establishing a group of patients with no incidence of metastases, the mitotic rate proved to be as good a factor as the prognostic index and better than tumor thickness or levels of invasion. The application of this prognostic index seems therefore to be useful in selecting for further treatment stage I melanoma patients with poor prognoses, eg, prophylatic lymph node dissection and immunochemotherapy.


Salabrasion of tattoos. A correlation of the clinical and histological results.

Twenty-six tattoos were treated by salabrasion. The salt was left on the abraded surface from zero to 24 hours. The percentage of residual pigment varied from 50%, when the salt was removed immediately after salabrasion, to 5%, when the salt was left in place for over 12 hours. When the salt was left on for variable periods, some degree of scarring and hypopigmentation occurred in 79% and in 59% of the tattoos, respectively. When the salt was removed immediately after salabrasion, 29% of the tattoos showed scarring and 29% showed hypopigmentation. Our results show that the best method is to remove the salt immediately after salabrasion, but that this form of therapy should only be done on those lesions where the eventual cosmetic result is not important.


Successful use of cyclophosphamide and prednisone for initial treatment of pemphigus vulgaris.

Previous reports showed that cyclophosphamide used late in the treatment of patients with pemphigus vulgaris reduced the complications due to steroids. In this study, cyclophosphamide was used in the initial treatment of five patients with pemphigus vulgaris in combination with prednisone to avoid side-effects of prednisone. Two patients had no prior treatment with steroids for pemphigus. Results indicate that initial combined program may be a highly effective treatment method for pemphigus vulgaris. Followup from one to four years after treatment shows all five patients in remission; four require no medication.


Speckled lentiginous nevus.

Speckled lentiginous nevus is, we feel, a distinctive nevocytic disorder and a clinical variety of nevus-cell nevus. The speckled areas show varying histological patterns that range from nevus incipiens to junctional and compound nevi. The background shows histological features of lentigo simplex. It is our contention that speckled lentiginous nevus should be separated from nevus spilus and nevus spilus tardus (Becker's), which we consider to be variants of epidermal nevus.


Nosocomial outbreak of scabies.

During the last quarter of 1976, a nosocomial outbreak of scabies occurred in a 558-bed community teaching hospital. There had been scattered reports of scabies throughout Michigan for nearly a year prior to this outbreak. The epidemic spread of scabies from a patient to 38 hospital employees and their families and associates was identified from historical, clinical, and microscopic skin preparation data.


Pyoderma gangrenosum. Abnormal monocyte function corrected in vitro with hydrocortisone.

A 34-year-old man with chronic active hepatitis and pyoderma gangrenosum demonstrated abnormalities in neutrophil and monocyte function. Monocytes from this man had diminished chemotaxis and bacterial phagocytosis. These functions were significantly improved in vitro after one hour of incubation of monocytes with 10(-5) hydrocortisone. Neutrophil function was nornal for bactericidal activity and phagocytosis, but neutrophil chemotaxis was diminished. A plasma inhibitor was not found to explain these phagocyte alterations.


Sarcoidosis associated with mycosis fungoides.

In November 1966, a 47-year-old black woman had a skin eruption and an abnormal chest roentgenogram that were found to be due to sarcoidosis. In September 1974, nodular lesions and subsequently generalized exfoliative dermatitis developed that were found to be due to mycosis fungoides. The concurrence of sarcoidosis and mycosis fungoides has been recorded only once in the literature. The depression of cell-mediated immunity found in this patient and other sarcoid patients suggests that impairment of the host's immunosurveillance system may predispose to the development of T-cell lymphomas.


Columnar epidermal necrosis. A special form of toxic epidermal reaction?

A bizzare erythematosquamous, partially verrucose, crustly or eroded eruption developed in a 6-year-old boy one week after his first measles vaccination. The eruption regressed completely after a two-year clinical course. Histologically, the epidermis showed unique columnar eosinophilic degeneration. There was a dense, mononuclear cell infiltration in the upper part of the dermis. To our knowledge these clinical and histologic features have not been reported in the literature, although they resemble, in some aspects, Kyrle's disease, Mucha-Haberman's disease, or lichen planus verrucosus. Regarding the pathomechanisms underlying the development of this unique epidermal change, a postulate was made that it represented a special form of toxic epidermal reaction, probably resulting from autoagressive lymphoid cell response to epidermal cells. Furthermore, relationship of measles vaccination to this special response is suggested.


Cutaneous manifestations of Noonan's syndrome.

Noonan's syndrome is a multisystem syndrome that has received little attention in the dermatologic literature, although there are numerous cutaneous manifestations that have been described. A typical case of Noonan's syndrome is presented. Clinical findings in this patient included short stature, curly scalp hair, prominent ears, hypertelorism, webbing of the neck, cubitus valgus, pigmented nevi, stasis dermatitis, and plantar hyperkeratosis. The latter two findings have not been previously reported in Noonan's syndrome. We urge that dermatologists become more aware of this syndrome to document the spectrum of changes that may occur in Noonan's syndrome.


Hereditary congenital hypopigmented and hyperpigmented macules.

Congenital hypomelanotic and hypermelanotic macules traced in three generations of a family suggested autosomal dominant inheritance. Some affected membbers also showed retarded growth and mental deficiency. Light microscopic findings of "splitdopa" preparations of lesional and normal skin were comparable, except that background staining of keratinocytes in dark macules was higher than in control skin. In light macules it was lower. Ultrastructurally, hypomelanotic skin showed small melanosomes (0.3 mu) that occurred in keratinocytes in melanosome complexes. Hypermelanotic skin revealed large melanosomes (0.6 mu) that were singly distributed in keratinocytes. Melanosome size in normal skin averaged 0.4 mu; distribution pattern was mixed. Melanin granules inside keratinocytes were fully melanized. Hyperpigmented, normal and hypopigmented skin of one person had histological features of black oriental and white skin. This clinical picture could well represent a new neurocutaneous syndrome different from tuberous sclerosis.


Acrodermatitis and acquired zinc deficiency.

A 42-year-old woman had an acquired zinc deficiency. The patient was malnourished, secondary to chronic alcohol (ethanol) abuse and cirrhosis, with associated low serum and urinary levels of zinc. Her acrodermatitis was unresponsive to topically applied triamcinolone acetonide but cleared after oral zinc sulfate therapy.


Monosymptomatic hypochondriacal psychosis manifesting as delusions of parasitosis. A description of four cases successfuly treated with pimozide.

A recent article in the Archives described the severe problems encountered in trying to treat patients with delusions of parasitosis. The present article describes four such cases, which fall into the larger category of monosymptomatic hypochondriacal psychoses, conditions that appear to be related to the paranoid disorders. Evidence is accumulating that such cases may respond very specifically to treatment with pimozide, a relatively new psychotropic medication. This drug keeps the symptoms in remission but does not effect a cure; nevertheless, it may represent a highly important advance in therapy in a condition traditionally regarded as virtually untreatable.


Dapsone-induced jaundice.

Enthusiasm in the use of dapsome for acne conglobata and other severe acne has created an increase in the use of this drug by dermatologists. We describe three patients in whom jaundice developed during dapsome therapy of 3 to 36 weeks' duration. Jaundice was due to cholestasis in two cases and to hemolysis in the third. These significant side effects call for careful observation by the physician if dapsone is to be used with safety.


Cows' milk-sensitive enteropathy.

Serial small intestinal biopsies related to withdrawal and challenge with cows' milk are described in 5 infants with cows' milk protein intolerenace. On the basis of these serial observations the existence of a cows' milk-sensitive enteropathy in infancy is clearly established. The cows' milk-sensitive mucosal lesion varied in its severity ranging from a partly flat mucosa to a mild degree of partial villous atrophy. Intraepithelial lymphocyte counts rose after a positive milk challenge, but on only one occasion to a level outside the normal range. The technique of serial biopsies related to dietary milk enables a firm diagnosis of cows' milk intolerance to be made upon the basis of a single milk challenge. Clinically this appears to be a temporary condition which disappears by the age of 2 years.


Value of monitoring plasma salicylate levels in treating juvenile rheumatoid arthritis. Observations in 42 cases.

Plasma salicylate concentration was monitored in 42 children on long-term salicylate therapy for rheumatoid arthritis. A given dose of salicylate per kg resulted in large variations in plasma levels, both between individuals and for a single individual at different times. The factors responsible for such variations were studied; in 6 cases urinary metabolites of salicylate were analysed. The relation between salicylate dosage and plasma half-life accounts for the fact that small changes in dosage can result in large changes in plasma concentration. The addition of corticosteroid or ACTH therapy results in lower plasma levels of salicylate, and necessitates higher dosage of salicylate. After the introduction of routine monitoring of plasma salicylate, the incidence of toxic symptoms fell sharply.


Ataxia telangiectasia. Evaluation of radiosensitivity in cultured skin fibroblasts as a diagnostic test.

The sensitivity to x-ray inactivation of cultured skin fibroblasts from clinically confirmed and suspected cases of ataxia telangiectasia was compared with that of cultures from normal subjects. The results confirm previous observations of an association between ataxia telangiectasia and enhanced in vitro radiosensitivity, and also suggest that clonal survival of x-irradiated cultures of skin fibroblasts is a valuable technique for confirming the diagnosis of the disease.


Accidental intra-arterial injection.

Accidental intra-arterial injection of intramuscular antibiotic preparations is described in 3 cases in infants. In 2 benzathine penicillin was injected, and in 1 rolitetracycline. The clinical features are dominated by arteriolar obstruction which produces gangrene of the most severely affected limb. In addition, neuroloigcal involvement occurs when vessels to nerves or spinal cord are involved. The arteriolateral aspect of the thigh is preferable to the buttock as a site for intramuscular injection, and a short (2.5 cm) needle should be used to minimise the risk of intra-arterial injection.


Urinary excretion of glomerular basement membrane antigens in Alport's syndrome. A new diagnostic approach.

Alport's syndrome is defined by the combination of hereditary nephropathy and neurosensory deafness, and is diagnosed from the family history combined with renal electron microscopy. Immunoelectrophoresis of the urine of 8 of 12 children suspected of Alport's syndrome showed a precipitation line moving into the beta-zone, applying an antiglomerular basement membrane antibody derived from an immunised rabbit. All patients who showed the typical pattern of Alport's syndrome on renal electron microscopy were among the 8 cases whose urine gave this immunoelectrophoresis pattern. Additionally, 5 of the mothers of the 8 children excreted the same antigen in their urine. The urine of 30 healthy children and of 10 patients with the idiopathic nephrotic syndrome did not show the presence of this antigen. This characteristic sign of Alport's syndrome may therefore be useful for its detection.


Metabolic response to cold in the newborn.

Blood concentrations of glycerol and free fatty acids were measured in healthy and sick 5-day-old infants during and after cold exposure. In apparently similar infants in similar circumstances, the blood concentrations varied widely. Although the concentrations of both glycerol and free fatty acids tended to be higher during cold exposure, it is not possible to use either as an index of cold exposure in individual infants.


Clubbing and whipworm infestation.

The association of clubbing, growth retardation, pallor, abdominal distension, and prolonged bloody diarrhoea with whipworm (Trichuris trichiura) infestation is described and discussed. Failure to recognise this association leads to misdiagnosis and unnecessary investigation.


Acquired toxoplasmosis in children.

Nine cases of acquired toxoplasmosis, 8 from rural backgrounds, are described, illustrating the wide variety of clinical pictures. Evidence of familial infection was found whenever sought, and was also found in cattle in one case. The availability of an easily performed screening test should make diagnosis of this common disease more frequent.


Serum complement components in Henoch-Schönlein purpura.

Serum levels of C1q, C4, C3, C5, factor B, and properdin were measured in patients with Henoch-Schönlein purpura (HSP). In the cases of acute HSP, 9 of 23 (39%) had a low CH50, and 5 of 17 (30%) a low properdin; C1q, C4, and C3 levels were not depressed. In 10 cases with chronic nephritis following HSP, complement components were normal except for 2 with reduced C4 and one with low properdin. These findings confirm that complement activation occurs in HSP; the low serum levels of properdin in the acute group indicate that there is activation of the alternative pathway in these patients.


Value of 1-hour blood-xylose test in diagnosis of childhood coeliac disease.

In a series of 46 children with untreated coeliac disease and in 102 controls with normal mucosa the 1-hour blood-xylose test was, in view of  its simplicity, of much value in the diagnosis of childhood coeliac disease. Only one blood-xylose result was falsely normal in the 46 coeliac patients. It is concluded that a normal blood-xylose value does not exclude coeliac disease and should not prevent peroral biopsy in the presence of strong clinical suspicion. On the other hand, patients who have repeatedly abnormal blood-xylose values merit an intestinal biopsy even in the absence of suggestive clinical symptoms.


Persistent neonatal hypoglycaemia due to glucagon deficiency.

In a newborn baby, suffering from persistent severe hypoglycaemia with convulsions glucagon deficiency was shown. Treatment with zinc-protamine-glucagon injection twice daily resulted in normal blood glucose levels. Motor development is delayed.


Peripheral pulmonary artery stenosis.

A term infant, born by caesarean section for fetal distress, developed grunting and cyanosis by 15 minutes of age. Ventilation at low pressures was achieved without difficulty but did not improve blood gas levels, and he died at 26 hours. Necropsy examination showed large heart and small lungs; histologically the lungs showed multiple obstructive lesions at medium size pulmonary artery level.


Estimating a worker entry interval for the carbamate pesticide furadan 4F insecticide.

Existing methods for the calculation of worker entry intervals by the use of kinetic data have focused on the anticholinesteratic organic phosphates. As carbamate pesticides share with these materials a common site for inhibition, the kinetic method was applied in estimating an entry interval for the carbamate, carbofuran, applied to citrus and grapes as Furadan 4F. No allowance was made for the more transient carbamylation of cholinesterase attributed to N-methyl carbamates, compared with the phosphorylation of the enzyme by organic phosphates. Thus, a measure of safety was built into the calculations which can then be used to establish safe reentry intervals to insure residue levels below the physiological threshold for cholinesterase inhibition.


Metabolism of trans-nonachlor and related chlordane components in rat and man.

The metabolic fate of trans-nonachlor and heptachlor in rats was studied in vivo and in vitro by using microsomal preparations of the liver. During in vivo studies the rate of excretion into urine and feces was monitored. The major metabolic products were collected from the feces and their chemical structures were determined by using various chromatographic and spectroscopic techniques. The immediate major metabolic product of transnonachlor is trans-chlordane which is further converted to 1,2-dichlorochlordene and to oxychlordane. From the latter metabolite, two major stable products, 1-hydroxy-2-chlorochlordene and 1-hydroxy-2-chloro-2,3-epoxy-chlordene are formed. Another route of metabolism is a direct formation of chlordene chlorohydrin which acts as a precursor for 1,2-trans-dihydroxydi-hydrochlordene. The major metabolic products of heptachlor were heptachlor epoxide, 1-exo-hydroxyheptachlor epoxide and 1,2-dihydroxy-dihydrochlordene.


The effects of a simulated refinery effluent on the grass shrimp, Palaemonetes pugio.

Duplicate static bioassays were conducted using a simulated refinery effluent on the grass shrimp (Palaemonetes pugio, Hippolyte sp.) with the LC-50 values recorded at 4-, 8-, 24-, 48-, and 96-hr intervals. The stimulated refinery effluent contained phenol (0.10 mg/L), sulfide (0.17 mg/L), chromium (0.25 mg/L), ammonia (10 mg/L), No. 2 fuel oil (10 mg/L), and kaolinite (20 mg/L). This arbitrary reference mixture (ARM) contains approximately the concentration of compounds recommended by EPA for 1977. Of the six ARM components, No. 2 fuel oil was the most toxic followed in decreasing order by sulfide, ammonia, phenol, chromium, and kaolinite. Temperature was the most important environmental variable affecting short term toxicity of the ARM to the grass shrimp. Light intensity, photo-period, and salinity had no significant effect. There was no difference in sensitivity of grass shrimp collected from five locations along the gulf and eastern coasts of the United States. Similarly, there was no difference in the response of two grass shrimp genera, Palaemonetes and Hippolyte to the ARM and there was no differences among the three species of Palaemonetes tested. In comparing the sensitivities of the two genera of grass shrimp and the pinfish (Lagodon rhombroides) to the ARM, the grass shrimp were more sensitive.


Mirex incorporation in the environment: in situ decomposition of fire ant bait and its effects on two soil macroarthropods.

The decomposition rate of fire ant baits and the consequent leaching of the pesticide mirex from the bait were investigated for one year in three types of environments (i.e., on the ground, in the soil, and in the pond) by means of the nylon litter bag method. There was no significant difference in the decomposition rates between toxic and non-toxic baits. The bait proved to be stable and slow to decay. After one year of exposure in the field, about 75% of bait material remained in the bags that were deployed on the ground, 60% in the soil, and 25% in the pond. The removal of mirex from the bait was due to leaching from, and natural decay of the bait. The loss of mirex from the bait to the environment varied significantly among the three habitats. At the end of 12 months, mirex disappearance from baits exposed on the ground was 41.1%, in the soil 56.3%, and in the pond 83.9%. The rate of mirex loss was slower during fall and winter. The toxicities of the bait decomposed in situ for different lengths of time (12, 9, 6, 3, and 0 months) to the land isopod Armadillidium vulgare and the soil millipede oxidus gracilis were higher than the undecomposed baits. This indicated that weathered mirex baits left in the field have greater biological impact than freshly applied baits, at least on the two soil animals tested.


Naturally-occurring heavy metal binding protein in invertebrates.

Low molecular weight cadmium, copper, and zinc binding protein has been isolated from the mussel Mytilus edulis in the cadmium polluted areas of Corio Bay adjacent to Melbourne. Its molecular weight and other properties suggest that it belongs to the metallothionein family of metal binding proteins. Its synthesis may have been induced in the cyctoplasmic solutions of the cells as a regulatory mechanism to avoid intoxication by excess uptake of any of the metals.


Host defense against opportunist microorganisms following trauma. II. Changes in complement and immunoglobulins in patients with abdominal trauma and in septic patients without trauma.

Total hemolytic complement (CH50), conversion of C3 by inulin and cobra venom factor (CoVF), and immunochemical levels of Clq, C4, C2, C3, C5, factor B, properdin, C3b inactivator (KAF), and immunoglobulins (Igs) G, A, and M were measured in the sera of ten patients with abdominal trauma and ten medical patients with septicemia without trauma. Reduction in C3 conversion by CoVF and decrease in the levels of properdin and KAF were demonstrated in the trauma sera. CH50 and the level of C5 were also decreased. Conversion of C3 by inulin and levels of factor B, Clq, C4, C2, and C3 were found to be normal in the patients' sera. Complement levels and activities were found to be normal in the sera of the septic non-trauma patients. A decrease in serum IgM was observed in both patient groups; levels of IgG and IgA were normal. These results indicated that abnormalities of immunoglobulin and of the alternative and classical complement pathways were associated with nonburn trauma. Moreover, the data suggested that consumption of the classical complement pathway associated with septicemia in the thermally injured patient resulted from synergism between the trauma and infection rather than from septicemia per se.


Experimental cryopreservation and autotransplantation of parathyroid glands: technique and demonstration of function.

A canine model for cryopreservation and autotransplantation of parathyroid glands was developed as a prototype for cryopreservation of human parathyroid glands; Each of 18 dogs had two parathyroids removed, sectioned, and cooled at a controlled rate to -80 degrees in media containing 10% dimethylsulfoxide and 10% autologous serum. After storage for two months at -196 degrees the tissue was thawed and implanted in muscle; the remaining two parathyroid glands were removed from the neck. Function was assessed by monitoring serum calcium levels and measuring parathyroid hormone levels in venous effluent from the graft beds. Autograft function was demonstrated in ten of 18 dogs; graft failure occurred in four dogs. In the remaining four dogs, function could not be evaluated because of accessory parathyroid tissue. Parathyroid tissue cryopreserved for nine months was documented to function in six of seven dogs. Histologic study of the cryopreserved, autografted tissue showed normal parathyroid architecture.


Esophagogastrectomy: data favoring end-to-side anastomosis.

Review of the literature since 1968 disclosed that the average mortality following esophagogastrectomy in 13 major institutions was 20%. Approximately half of the deaths were attributed to leaks from the esophagogastric anastomosis. Further analysis of the literature revealed that both the rate of anastomotic leakage and the rate of mortality were lower in end-to-side esophagogastric anastomoses as compared to the end-to-end type. Study of the author's personal consecutive series of 36 cases tends to confirm this finding.


Hepatic inactivation of vasoactive intestinal peptide in man and dog.

IN AN EFFORT TO DOCUMENT THE ROLE OF THE LIVER IN THE CATABOLISM OF VASOACTIVE INTESTINAL PEPTIDE, SEVERAL DIFFERENT TYPES OF EXPERIMENTS WERE CARRIED OUT, INCLUDING: 1) simultaneous measurement of portal and systemic immunoreactive vasoactive intestinal peptide, both in the basal state and following calcium stimulation; 2) by measuring plasma concentrations of immunoreactive vasoactive intestinal peptide before and after portacaval shunt; 3) by measuring plasma VIP before and after portacaval shunt following calcium, prostigmine and pentagastrin stimulation; 4) by determining plasma VIP levels in patients with liver disease and in hepatic failure, and in patients with variceal hemorrhage before and serially after portal systemic shunt; 5) by measuring CSF vasoactive intestinal peptide in dogs before and after portacaval shunt and when the animals finally succumb to hepatic failure. The results consistently suggest that the shunting of portal blood away from the liver does not result in significant elevation of basal peripheral plasma levels of vasoactive intestinal peptide. Following stimulation however, increased amounts of peripheral plasma VIP are detected, following calcium, pentagastrin and prostigmine release of VIP. Portal vein levels are always significantly higher than peripheral plasma VIP again, confirming a catabolic role for the liver. In patients, elevation of peripheral plasma VIP is seen in hepatic failure, but not after portacaval shunt. Finally, cerebrospinal fluid VIP is elevated in dogs following hepatic failure, confirming the presence of a neural-gut axis and suggesting an influence of hepatic catabolism of VIP not only in the periphery, but also within the central nervous system.


Inhalation injury--an increasing problem.

Inhalation injury is a common complication of thermal accidents occurring in one-third of patients burned. The routine use of fiberoptic bronchoscopy on all patients incurring thermal burns provides an accurate and safe means for diagnosis. Although complications for inhalation injury are common, the mortality can be reduced by early diagnosis and attention to careful fluid resuscitation, aggressive pulmonary therapy and the avoidance of prophylatic steroids.


Results of esophagocardioplasty with gastric patch in the treatment of esophageal achalasia.

Since 1968 esophagocardioplasty with gastric patch was employed in 57 patients as a primary operation for achalasia of the esophagus and eight patients with previous operations for achalasia. Satisfactory results were obtained in follow-up studies up to eight years. The results indicate that this procedure is successful in dilating the lower part of the esophagus and esophagocardiac junction without interfering with their proper functions. This provides better passage through the junction with preservation of the mechanism which prevents reflux.


Endarterectomy of the popliteal artery for segmental occlusive disease.

Segmental occlusive disease though limited to the popliteal artery gives rise to significant ischemic symptoms such that surgical treatment is indicated. Endarterectomy with vein angioplasty was the primary procedure in 76 patients (79 limbs) over the past 15 years. Augmentive lumbar sympathectomy was performed in 30 patients. Endarterectomy restoration was successful in 73 patients (76 limbs). Acute postoperative thrombosis occurred in six limbs, four were restored, one survived, one underwent delayed amputation. Long term failures developed in 18 limbs, four were restored, 11 survived without further treatment, and three were amputated. All limbs were classified according to stages of outflow obstruction and extent of endarterectomy; however, there was no meaningful pattern of correlation with failures except to note that amputations occurred only in advanced stage III obstructions. Thirty-two patients (43%) were restudied by arteriography. Cumulative patency rate for 79 limbs at risk at five years was 75.6%, at ten years, 58.5%. Restoration of popliteal patency can be accomplished by endarterectomy with results comparable to femoral-popliteal saphenous vein graft for more proximal lesions. Endarterectomy affords the advantage that a bypass procedure can still be performed in most failures as the long saphenous vein, not sacrificed initially, is still available.


Iatrogenic internal hernia involving the iliac artery.

Four months postradical lymphadenectomy and pelvic irradiation for Stage I teratocarcinoma of the testis, a patient was found to have an internal strangulated herniation of small bowel beneath the right iliac artery. The operative management is discussed, and the literature is reviewed concerning the etiology of small bowel obstruction in postoperative, irradiated patients and the techniques of peritoneal closure.


Cloacogenic carcinoma.

Cloacogenic carcinoma is a rare tumor of the anorectal region originating from a persistant remnant of the cloacal membrane of the embryo. The tumor accounts for 2-3% of anorectal carcinomas and occurs more than twice as often in women. Most tumors present as fungating or ulcerating lesions, but the tumor may arise in anal ducts and present as a submucosal mass. Wide abdominoperineal resection is the treatment of choice with a five year survival of 50%. Metastases occurs to the inguinal lymph nodes in more than 50% of the patients at sometime during the course of the disease with distant metastases occuring most commonly to liver and lungs.


Clinical pharmacology of intravenous and intraperitoneal aminoglycoside antibiotics in the prevention of wound infections.

Seventeen patients had intraoperative peritoneal lavage with a solution containing one gram of kanamycin in 200 ml of 0.9% NaCl. The solution was removed by suction at two or five minutes. Venous blood samples were obtained at 15 minute intervals for two hours following lavage. Despite diligent attempts, an average of only 60% of the solution was recovered by suction. The peak concentration of kanamycin in serum correlated directly with the kanamycin dose (p less than 0.025). In six patients lavaged for five minutes, peak absorption occurred at 15 minutes with serum concentrations of 20.3 +/- 2.0 microgram/ml. In five patients lavaged for two minutes insignificantly (p greater than 0.1) lower peak serum concentrations (15.3 +/- 1.8 microgram/ml) occurred at 15 minutes. Six additional patients had peak kanamycin serum concentrations which occurred at 75 minutes and reached 23.2 and 24.0 microgram/ml in two patients. In three patients who received intravenous gentamicin prior to surgery, nine paired serum and peritoneal fluid samples obtained during three hours preceding lavage showed no significant differences in gentamicin concentrations (p less than 0.5). These pharmacokinetic data demonstrate the penetration of parenterally administered aminoglycosides into intraoperative peritoneal fluid. Kanamycin lavage for wound prophylaxis should be used cautiously and should be abandoned in patients who have renal impairment where prolonged toxic serum concentrations could develop.


Abdominal aortic surgery in the presence of a horseshoe kidney.

Prior experience with the rare combination of horseshoe kidney and significant atherosclerotic vascular disease suggests difficulty in intraoperative management, often requiring division of the renal isthmus or sacrifice of some renal tissue. Seven patients have been managed successfully over the past ten years at The Ohio State University Hospital. There were six men and one woman, ranging in age from 39 to 66 years. Of the five patients with abdominal aortic aneurysm, four had a pulsatile abdominal mass, three had abdominal pain, and one had back pain. The other two patients had progressively symptomatic aortoiliac disease. All seven patients had hypertension, easily controlled by medication. Critical diagnostic procedures are preoperative intravenous pyelogram (IVP) and abdominal aortic arteriogram. The IVP detected the previously unsuspected diagnosis in 100% of the cases. The arteriogram accurately located the aneurysm in relation to the renal vascular supply, and disclosed aberrant blood supply in three of four patients with aberrant vessels. All seven horseshoe kidneys were fused at the lower pole. The operative approach involves meticulous dissection of the aberrant blood supply to the kidneys, and mobilization of the isthmus for adequate retrorenal aortic exposure. In six of the seven patients, the grafts were placed posterior to the isthmus. There were no deaths, and there were no complications related to the presence of the horseshoe kidney. In three of the seven patients, hypertension improved. Patients with horseshoe kidney and aortic disease may be safely operated upon without damage to the kidney. IVP and selective angiography are essential to provide preoperative information.


Femoropopliteal vein grafts for claudication. Analysis of 100 consecutive cases.

One hundred consecutive femoropopliteal venous grafts in 85 patients with claudication were followed for five years. At this time, three limbs had been amputated, approximately one quarter of the patients had expired, and 70% of the grafts in surviving patients remained patent. It is concluded that this operation does not appear to increase the risk of amputation and in fact, may lessen it. Moreover, it is associated with minimal risk and generally provides long term relief of claudication, thus enhancing the quality of life in most patients.


Percutaneous cytodiagnosis of carcinoma of the pancreas and bile duct.

Fifty-one percutaneous fine-needle aspiration biopsies guided by selective angiography and 57 by percutaneous transhepatic cholangiography (PTC) were performed in 88 patients. Fifty-two of the patients had a tumor localized to the pancreas and 19 a tumor of the extrahepatic biliary tract. In 17 patients the suspicion of neoplasia was possible to rule out. In 60% of the patients with pancreatic carcinoma and in 53% of the patients with biliary duct carcinoma correct cytological diagnosis was obtained. No false positive results were found. The diagnostic reliability was the same under guidance of angiography as PTC. The experience of the examiner markedly influenced the accuracy of the method. Exact correlation between the cytologic and histologic reports was found in cases where representative material was obtained at the aspiration. None of the 108 punctions was followed by complications. Since the method is harmless and has a high success rate especially in experienced hands it is an important adjunct to the management of pancreatic and bile duct lesions.


Host defense against opportunist microorganisms following trauma. I. Studies to determine the association between changes in humoral components of host defense and septicemia in burned patients.

Total hemolytic complement (CH(50)), conversion of C3 by inulin, and immunochemical levels of Clq, C4, C2, C3, C5, factor B, C3b inactivator (KAF), and properdin were measured in the sera of 15 patients with severe thermal injury during nine weeks postburn. Five of the 15 patients had multiple episodes of septicemia as documented by positive blood cultures and clinical findings. Decrease in CH(50), Clq, C4, C2, C3, and C5 occurred prior to and during septic episodes in these patients. Although conversion of C3 by inulin was often reduced during septic episodes, levels of factor B and KAF were generally normal or elevated. In only one patient did consumption of complement occurring during septicemia decrease the opsonic capacity of the patient's sera for the patient's infecting microorganism, an isolate of E. coli; sera from the same patient opsonized her infecting strain of S. aureus normally. The microorganisms isolated from the other septic patients, which were opsonized normally by the patients' sera despite complement consumption, were also with one exception strains of Staphylococci. In the nonseptic burned patients, decrease in properdin and C3 conversion by inulin, and increase in C3, factor B and KAF were demonstrated as we have previously reported. The results indicate that the classical complement pathway was activated during septicemia in burned patients and that activation of this pathway occurred preferentially due to inhibition of the alternative pathway. In addition, the data show that complement consumption may reduce the opsonic capacity of a patient's sera for certain microorganisms and not for others.


Intravenous fat tolerance in hepatic schistosomiasis.

The elimination rate of lipid after a single intravenous dose of an artificial fat emulsion was studied in 13 schistosomal patients and 13 controls. A strikingly significant lower level was found in the mean incremental values of TG ten minutes after injection in the schistosomal patients than the controls. The shape of the curve up to 120 minutes after injection was of zero order in the controls but exponential in the schistosomal patients. The possible factors responsible for these differences are discussed.


Study of chemical constituents of thoracic duct lymph in schistosomal hepatic fibrosis.

Concentrations of serum and thoracic duct proteins, immunoglobulins, lipids, enzymes and electrolytes were estimated in 15 patients with schistosomal hepatic fibrosis and presinusoidal obstruction and in 12 controls. There was a significant decrease of thoracic duct total proteins, albumin and triglycerides, with marked and significant increase in IgG and IgM in SHF, compared to the controls. The levels of transaminases, alkaline phosphatases and inorganic phosphorus were significantly higher in the lymph of SHF patients compared with healthy controls. It is presumed that these changes represent the pattern of lymph constituents in presinusoidal obstruction.


Experimental studies on the suitability of aquatic snails as intermediate hosts for Paramphistomum cervi in Iraq.

Three of the most common species of aquatic snails in Iraq were examined for their susceptibility to infection with Paramphistomum cervi. Bulinus truncatus was the only susceptible species. No development occurred in Physa acuta or Lymnaea lagotis euphratica. These findings and a previous field observation that infection of B. truncatus with amphistome larvae is not uncommon indicate that B. truncatus is an intermediate host of P. cervi in Iraq. Young snails of B. truncatus were more susceptible to infection than older ones.


Histochemical differentiation of Brugia, Wuchereria, Dirofilaria and Breinlia microfilariae.

Histochemical demonstration of acid phosphatase activity in microfilariae gives sufficiently characteristic and consistent results for the differentiation of even closely related species. No difference could be detected among nocturnally periodic, nocturnally subperiodic and diurnally subperiodic Brugia malayi, but they could readily be distinguished from B. pahangi. Similarly, Dirofilaria repens could be readily distinguished from D. immitis and B. booliati from B. sergenti. The enzyme distribution pattern of a Malaysian rural strain of Wuchereria bancrofti was different from those of other regions.


Studies on the immature stages of the Simulium neavei Roubaud complex and their associated crabs in the Eastern Usambara Mountains in Tanzania. IV. Observations on the crabs and their attached larvae under exceptionally dry conditions.

When exceptionally low rainfall resulted in the drying out of some 'permanent' streams containing the immature stages of Simulium neavei complex species, the fate of the larvae and their associated crabs was investigated. Both crabs and larvae survived under rocks, stones and boulders where some moisture persisted. Such situations would be out of reach to insecticides applied to running water in the normal way.


The micro-ELISA technique in the serodiagnosis of visceral leishmaniasis.

The micro-scale Enzyme-linked Immunosorbent Assay (micro-ELISA) technique, with alkaline phosphatase as a marker enzyme, has been used for the serodiagnosis of human and canine visceral leishmaniasis, from foci in southern France. This technique which uses a soluble antigen is highly sensitive, with a degree of specificity slightly higher than that of the IFA. It is suggested that the micro-ELISA procedure can be added to the battery of serological techniques and would be particularly useful for large scale epidemiological studies of leishmaniasis.


The development of Schistosoma haematobium in the hamster.

The in vivo development of Schistosoma haematobium in the hamster was studied. Six stages of development were distinguished on the basis of morphological and histochemical criteria. Schistosomula reached the lung (stage 1) on day three post-infection, with maximum concentrations on day nine. Gut formation occurred in the second stage at day 18. In stage 3 'Organogeny' (day 24) males developed one testis and females a narrow uterus. Pairing and the development of males with sperm-containing testes and females with an ovary characterize stage 4 (day 28). In stage 5 (day 53) vitelline follicles begin to develop in the females. The final stage, oviposition, occurred on days 61-63 and was characterized by the appearance of fully developed eggs in the uterus.


The in vivo development of Schistosoma bovis in the Nile rat.

The in vivo development of the Sudanese strain of Schistosoma bovis in the Nile rat, Arvicanthus niloticus is described. Six stages in development are distinguished: the 'lung form' (stage 1), attaining maximum numbers on day 5 post-infection; the 'closed-gut form' (stage 2) on day 14, characterized by the union of the gut caeca behind the ventral sucker; 'organogeny' (stage 3) on day 17, the male possessing one testis and a gynaecophoric canal and the female a narrow uterus; 'gametogeny' (stage 4) on day 26, with pairing, the male having four fully developed testes and the female an ovary; 'egg-shell formation' (stage 5) on day 35; 'oviposition' (stage 6) on day 37, with the female showing uterine eggs. The time to complete in vivo development in the Sudanese strain of S. bovis is more rapid than in the Israeli strain, 37 and 42 days respectively.


Studies on the enzyme linked immunosorbent assay (ELISA) test for Schistosoma mansoni infections.

Extensive studies of the use of the ELISA test for the detection of antibodies in Schistosoma mansoni infections are described. A method has been evolved for the determination of the optimum value for the reference serum endpoint. In chimpanzees infected with S. mansoni a crude egg antigen detected antibodies earlier in the infection than did a worm antigen and was generally more reactive. The ELISA test, using the egg antigen, has been applied to sera from populations infected with S. mansoni, with other human schistosomes, or with helminth infections other than schistosomiasis. The ELISA test was as sensitive as the IFAT and CFT, but more specific. However, many cross-reactions occurred in infections with other human (and with animal) schistosomes, although to a lesser extent with other helminths. In surveys in the Sudan the use of blood collected on absorbent paper was only slightly less sensitive for the detection of antibodies than sera, and this technique showed that the prevalence of infection was higher than that measured by stool examination alone. Possible future developments are discussed with a view to improving sensitivity and specificity both for clinical and epidemiological work.


Genetics of a new mutant, curved wing, of the mosquito Aedes togoi.

A new recessive mutant curved wing (c) in the mosquito Aedes (Finlaya) togoi (Theobald), a vector of various species of filariae in the Far East, has been shown to be linked to yellow larva (y), with a recombination value of 13.26 +/- 1.41 to 20.53 +/- 1.41%. These linked alleles are inherited independently of either sex (M), straw-coloured larva (s), ruby eye (ru), or pigmented pupa (p). Evidence has now been produced that sex (M)-s, ru-p, and y-c mark the three linkage groups in this species (2n = 6), and these markers, respectively, have been placed provisionally in linkage groups 1, 2, and 3.


Some methods for membrane feeding of laboratory reared, neotropical sandflies (Diptera: Psychodidae).

A brief introduction to the history and applications of membrane feeding is given, together with its use to feed and infect sandflies with Leishmania. The present paper describes methods for feeding Lutzomyia longipalpis and Lu. flaviscutellata through membranes. Of the membranes tested, chick skins and bat wings gave the best results. Membranes stored at -20 degrees C for over a year were found to be less effective than fresh ones. Blood meals were maintained at temperatures between 24 degrees C and 37 degrees C and it is concluded that although temperatures as high as 37 degrees C are unnecessary for successful membrane feeding of sandflies, fewer flies feed in most instances at temperatures below 27 degrees C. The influence on feeding of individual skins, different lots of blood and the addition of leishmanial cultures to offered blood are discussed.


A light and electron microscope study of rickettsia-like organisms in the ovaries of mosquitoes of the Aedes scutellaris group.

The ovaries from some members of the Aedes scutellaris group were examined by light and electron microscopy to locate rickettsia-like organisms, and Culex pipiens fatigans was used as a control. It was found that light microscopy was unsatisfactory for this purpose since none of the available staining techniques demonstrates the organisms clearly and diagnostically. With the electron microscope it was shown that the organisms were by no means as common in the mosquitoes of the A. scutellaris group as in C.p. fatigans; they were quite frequently seen in A. polynesiensis, of sporadic occurrence in A. malayensis, rare in A. tabu and have not yet been identified with certainty in A. cooki.


The ultrastructural basis of abnormal development of Brugia pahangi in refractory Aedes aegypti.

Cuticular abnormalities in larval Brugia pahangi at c. 12 hours post blood meal are the first signs of abnormal worm development in refractory Aedes aegypti. Normally developing B. pahangi undertakes large scale cuticular reorganization during the first larval stage, screting new cuticle to nearly six times the original volume. The inability of the first stage larva to carry out this cuticular reorganization in refractory A. aegypti is the basis of developmental abnormality. It is concluded that this failure on the part of the worm is caused by an alteration in the physiological environment of the flight muscle cells of refractory A. aegypti from that of susceptible A. aegypti.


Multiple valve replacement: changing status.

Review of our experience with multiple valve replacement over a 6-year-period revealed a recent marked reduction in operative risk. Operative mortality for 62 patients operated on before 1974 was 34%; for 44 patients operated on since 1974, mortality was only 11%. In both groups, mortality was clearly related to the preoperative cardiac functional status. Several recent technical advances including myocardial protection by topical hypothermia, shortened perfusion time, and the intraaortic balloon pump may all have contributed to the reduced operative risk.


The Blalock-Taussig shunt in the first two years of life: a safe and effective procedure.

Many surgeons have been reluctant to perform Blalock shunts in patients who are in infancy or early childhood (less than 24 months old) and have done instead direct aortopulmonary anastomoses. Recently, others have advocated complete repair of tetralogy of Fallot in early infancy because of the high mortality of direct aortopulmonary shunts. We believe the Blalock-Taussig anastomosis is a safe and effective palliative procedure for all infants with inadequate pulmonary blood flow regardless of size. During the past nine years, 24 babies less than 2 years old who were followed had construction of Blalock-Taussig anastomosis for inadequate pulmonary blood flow. There were no operative deaths and no shunt-related late deaths. Of the 24 babies, 12 were less than 12 months old. Eighteen of the 24 had tetralogy of Fallot. The remaining 6 had a variety of lesions with inadequate pulmonary blood flow. The mean weight of the entire group was 7.3 +/- 1.6 kg. Of those infants less than 12 months old, the mean weight was 6.8 +/- 2.0 kg. More than 6 months following construction of the shunt, 2 babies died from sepsis unrelated to cardiovascular status. All infants had adequate but not excessive pulmonary blood flow after shunting. There were no late shunt failures.


The effectiveness of surgical treatment of acute aortic dissection.

Ten consecutive patients have undergone operative repair of acute aortic dissection at St. Thomas Hospital in the last three years. Two died. To assess the status of the residual aorta, all 8 survivors were evaluated by postoperative aortography. Only the patient with a clotted dissection on preoperative study showed no residual dissection of the distal aorta. Analysis of postoperative aortograms suggests that the original dissection reentry points become sites of inflow following removal of the original intimal tear. No death resulted from these residual abnormalities. Retrograde dissection and aortic insufficiency were obliterated. The major sites of aortic rupture were removed. It is concluded that surgical therapy for acute aortic dissection is effective in that it avoids the major sources of mortality. The resultant surviving population must be carefully observed in view of the high frequency of residual aortic abnormality.


Extraluminal or intraluminal inferior vena cava occlusion in pulmonary embolism.

Twenty-five cases of extraluminal and 47 of intraluminal inferior vena caval (IVC) occlusion for management of pulmonary embolism were reviewed. A comparison of results obtained with both methods suggests that the IVC umbrella filter provides the safer, more reliable means of IVC interruption in patients whose condition fulfills the criteria for caval occlusion. The simplicity of this technique and the fact that it can be performed under local anesthesia justify its consideration as the procedure of choice for IVC occlusion and permit its use in severely ill patients. On the basis of our positive findings, we now recommend that extraluminal occlusion be reserved for patients in whom insertion of the IVC umbrella is technically impossible.


Development of a practical membrane lung system.

The purpose of this study was to evaluate a compact, single-pump membrane oxygenator system designed for both short-term open-heart procedures and long-term extracorporeal support. Work was directed at developing a compatible, disposable venous reservoir, fabricating a compact mounting board, determining acceptable priming volumes, and establishing safe and effective modes of setup and operation. Ten adult baboons undergoing total cardiopulmonary autotransplantation as part of a separate study were operated on using a 1.5 m2 Kolobow spiral-coil membrane system. Blood gases, oxygen transfer, extracorporeal blood flows, priming volume, and setup times were determined. In addition, 3 infant and 6 adult human subjects undergoing cardiac operations in which spiral-coil membranes of various sizes were used were also similarly studied. The data and experience from these studies suggest that the spiral-coil membrane system utilized is safe and effective in procedures requiring short-term cardiopulmonary bypass.


Thoracoscopy: a useful tool in the diagnosis of thoracic disease.

During a 12-month period, 11 patients underwent diagnostic thoracoscopy for previously undiagnosed thoracic disease. In all patients, the diagnosis had been unobtainable by the usual diagnostic modalities of bronchoscopy, scalene node biopsy, mediastinoscopy, thoracentesis, or closed pleural biopsy. Thoracoscopy was diagnostic in 10 of the 11 patients. There was no morbidity or mortality. In all patients the indication for thoracoscopy was suspected malignancy. The majority of patients had recurrent pleural effusions in which routine cytological studies and tissue biopsies had been nondiagnostic. Pathological findings were mesothelioma in 3 patients, primary carcinoma of the lung in 4, congestive heart failure with pleural effusion in 1, metastatic carcinoma in 2, and inflammatory disease in 1 patient. Indications, techniques, and results are discussed. Thoracoscopy is a valuable tool in the diagnosis of thoracic disease; with it, unneccessary thoracotomy can often be avoided.


Correction of pectus excavatum without prostheses or splints: objective measurement of severity and management of asymmetrical deformities.

From 1949 to 1977, 254 children underwent surgical reconstruction of pectus excavatum by means of a variety of operations at The Johns Hopkins Hospital. From 1970 to 1977, 68 children had a modified Ravitch repair, with the addition of a tripod internal fixation technique for support of the sternum. These children obtained excellent cosmetic reconstruction without prosthetic support or splints. During an 18-month period we used a new system of caliper measurement of the spatial anatomy of the thoracic cage in more than 50 children. During the same period, we originated an operative step to correct the not uncommon asymmetrical excavatum that is usually deeper on the right and associated with a troublesome rotation of the sternum, found in 9 of the last 27 children seen. Correction was accomplished with an oblique anterior sternal osteotomy. The groups were analyzed and compared with respect to age, postoperative complications, and end results in order to identify trends in the management of children with this condition. On the basis of this experience, we feel confident in recommending a standardized operation for all forms of pectus excavatum at an elective age between 4 and 6 years and without prosthetic splints.


Marlex mesh support for the correction of very severe and recurrent pectus excavatum.

A method for the correction of very severe and recurrent pectus excavatum is presented. The technique consists of mobilization of the sternum, transverse osteotomy, parasternal resection of the costal cartilages (modified Ravitch procedure), followed by placement of Marlex mesh behind the sternum and suturing the edge of the Marlex mesh to the peripheral stump of the resected ribs. This method has been used with good results in 6 patients, 2 of them with recurrent deformities.


Placement of pericardial drainage tube for the treatment of pneumopericardium in the neonate.

A method for resolving the life-threatening complication of neonatal pneumopericardium is described. In patients suspected of having this complication, needle aspiration of the pericardial sac should be performed to confirm the diagnosis. Then a tube should be inserted directly into the sac, attached to continuous-suction drainage, and allowed to remain in place until positive end-expiratory pressure is discontinued. The technique has not been associated with morbidity, mortality, or recurrence of pneumopericardium.


Cervical aortic arch with retroesophageal aortic obstruction: report of a case with successful surgical intervention.

The clinical, roentgenographic, hemodynamic, and angiographic features of a patient with a right cervical aortic arch and retroesophageal aortic obstruction associated with a ventricular septal defect are presented. Surgical relief of the aortic obstruction was successfully achieved by placement of a bypass graft between the left common carotid artery and the descending thoracic aorta.


Evaluation of the Hunter-Sessions self-retaining aortic cannula.

A report of our experience with a new self-retaining aortic cannula is presented. We have used this cannula in more than 30 patients and found it to be very secure and convenient for rapid cannulation since no pursestring sutures are required for initial placement.


Surgical correction of refractory reflux esophagitis using the standard unmodified Belsey Mark IV technique.

The treatment of symptomatic hiatus hernia unresponsive to medical treatment has been refined in the last decade. The work of Hill and colleagues in investigating the pathophysiology of this problem, and the anatomical techniques developed by Dr. Nissen and Mr. Belsey, have reduced the recurrence rate in the surgical management of symptomatic hiatus hernia to the point where it is at least as low as that for surgically treated duodenal ulcer. The most commonly employed methods of surgical repair for symptomatic hiatus hernia are those advocated by Drs. Nissen and Hill and Mr. Belsey, which are superior to the many unmonitored methods employed in the past. Recently, the use of modifications of these techniques has been reported in the literature with short follow-up studies. The current communication relates one surgeon's experience treating 85 consecutive patients with refractory reflux esophagitis using the standard unmodified Belsey Mark IV repair as originally described by Mr. Ronald Belsey of Bristol, England. Details of this repair are presented.


The modified Collis-Nissen operation for control of gastroesophageal reflux.

An operation employing the Nissen fundoplication performed about an undivided 5 cm gastroplasty tube created with a gastrointestinal anastomosing (GIA) stapler that was modified by elimination of the cutting blade has been devised and evaluated in 48 patients over a period ranging from 3 to 52 months (average, 27 months). Seventeen of these patients had severe esophageal strictures. Reflux control, evaluated by clinical appraisal and roentgenograms in all patients and by 24-hour esophageal pH monitoring in some, has been complete in all patients throughout the study. One patient with undetected subclinical achalasia continues to have mild dysphagia and represents the only unsatisfactory result in the series. Normal swallowing has been restored to all patients with strictures, and the others remain free of symptoms. The simplicity, reproducibility, and effectiveness of this operation warrant its continuing evaluation.


Effects of pulsatile assistance and nonpulsatile flow on subendocardial perfusion during cardiopulmonary bypass.

We compared the effects of pulsatile and nonpulsatile perfusion in 12 dogs on extracorporeal circulation. In beating empty and fibrillating hearts at 37 degrees and 28 degrees C, coronary blood flow was measured by flowmeter and microspheres at diastolic pressures ranging between 50 and 130 mm Hg. At fixed systemic flow rates (range, 600 to 2,400 ml/min), pulsatile perfusion produced a transient (3 to 4 second) augmentation of diastolic pressure and then resulted in the following: (1) decreased peripheral vascular resistance (p less than 0.05); (2) unchanged peak diastolic pressure (compared with nonpulsatile perfusion); (3) decreased mean aortic pressure (6 to 37%) (p less than 0.05); (4) decreased coronary blood flow (10 to 45%) (p less than 0.05); and (5) decreased subendocardial blood flow (from 512 to 438 ml/100 gm/min) (p less than 0.05). Pulsatile perfusion in beating hearts (37 degrees or 28 degrees C) did not reduce subendocardial vascular resistance, but did improve subendocardial perfusion by 27% and 36% in fibrillating hearts at 37 degrees and 28 degrees C, respectively. We conclude that with the exception of ventricular fibrillation, pulsatile assistance offers no advantage over nonpulsatile perfusion and has the potential disadvantage of requiring higher pump flow rates to achieve any desired level of coronary and subendocardial flow.


Surgical treatment of annuloaortic ectasia with composite grafts including homologous dura mater valves.

We describe 3 patients in whom a composite dura mater valve-Dacron tube graft was used for replacement of the entire ascending aorta and aortic valve. Two patients had Marfan's syndrome and 1, a chronic aortic dissection, type II. All had severe aortic regurgitation. There were no early or late deaths in a follow-up period of 2, 7, and 12 months, respectively. All 3 patients were asymptomatic when last seen. Two underwent postoperative aortography that disclosed well-functioning valves and good filling of the coronary arteries. It is concluded that annuloaortic ectasia is best treated by the technique of total replacement of the ascending aorta and aortic valve by a composite valve-tube graft, and that the homologous dura mater valve, for its characteristics of central flow, lack of need for anticoagulants, and durability, represents a reasonable alternative for use in this situation.


Heterologous pericardium for the closure of pericardial defects.

Patches of glutaraldehyde-preserved porcine pericardium were transplanted orthotopically into 20 dogs to see if they might make a satisfactory pericardial substitute. Two dogs had mediastinal infections and were excluded from this study. All animals were reoperated on at regular intervals between 15 and 300 days. In 15 dogs there were no adhesions between the porcine pericardium and the host's epicardium. Histological study showed healing between both pericardiums and no degenerative changes in transplanted pericardium. Glutaraldehyde porcine pericardium has been utilized in 8 patients to close the pericardial cavity. There have been no problems related to the pericardial grafts after a maximum follow-up of 9 months.


Delayed postoperative cardiac tamponade: diagnosis and management.

Symptoms and signs of decreased cardiac output associated with an elevated venous pressure should alert one to the possibility of delayed cardiac tamponade. Enlargement of the cardiothoracic ratio shown by serial roentgenograms and demonstration of significant pericardial effusion by echocardiogram or radionuclide angiocardiography support the diagnosis. Erratic response of the prothrombin time to administration of warfarin and abnormal results of liver function test are additional clues to its diagnosis. Right heart catheterization documents the presence of tamponade and excludes other diagnostic considerations. Operative decompression of the pericardial space can be accomplished by pericardicentesis, subxiphoid pericardiotomy, median sternotomy, or thoracotomy. Hemodynamic observations following the relief of tamponade assure that an adequate therapeutic procedure has been performed.


Intraoperative pacemaker electrical testing.

To determine the clinical value of intraoperative pacemaker system electrical testing, the results of 200 consecutive pacemaker procedures (95 ventricular and 6 atrial primary implantations, 88 generator replacements, and 11 system revisions) were reviewed. The rationale and technique of testing maneuvers are described, including the use of a compact pacing system analyzer wrapped and used on the sterile operating field.


Sinus venosus atrial septal defect associated with partial anomalous pulmonary venous drainage: surgical repair.

This report descrbies a new technique for the repair of sinus venosus atrial septal defect associated with partial anomalous pulmonary venous drainage. A right atrial wall flap is used both to deflect the anaomalous venous blood into the left atrium and to close the atrial septal defect. Then an atrioplasty is performed. This method does not employ any foreign materials, avoids injury to the sinoatrial node and internodal tracts, and minimizes the risk of obstruction of the ostia of the anomalous pulmonary veins and superior vena cava.


Left axillary incision (minithoracotomy) for PDA division.

From 1955 to 1975, 417 patent ductus arteriosus (PDA) operations were performed at Sapporo Medical University. The last 118 operations (28.3%) were done by division through the left axillary incision without mortality. Forty patients were less than 2 years old and 14 were less than 1 year old. The ratio of girls to boys was 3.5:1. Because the majority of patients with PDA are girls, parents commonly show considerable concern over the size of the operative scar. Our clinical experience demonstrates clearly the feasibility and safety of an axillary incision in dividing a PDA, even in premature infants. A minithoracotomy through the axilla is recommmended.


[Cerebral venous thrombosis].

A review of cerebral phlebothrombosis using material from the pathology departments of the National Institute of Cardiology and the General Hospital in Mexico City is presented. The most frequent causes found were: post partum. Secondary to congenital heart disease and associated with infections. In both institutions the most frequent anatomical find was thrombosis of the superior longitudinal sinus. Isolated venous thrombi in the brain probably takes place more frequently than reported. Hemorrhagic necrosis in brain tissue is the most frequent microscopic finding, associated in variable degrees with edema and anoxic encephalopathy. A description of clinical and angiographic findings is presented.


[Ultrastructural observations on experimental shock lung].

Intercellular junctions in the alveolar epithelium and in the capillary endothelium in the dogs after hemorrhagic shock (mean BP 40 mm Hg for 3 hours) and from control dogs were observed in the electron microscope using the freeze-fracture and etch technique. Following shock, tight junctions (zonulae occludentes) in the alveolar epithelium which were well developed with may strands in control animals showed alterations in substructure. Some desintegration and disappearance of junctional strands in "focal" regions were occasionally observed in the endothelium as well. The increased pulmonary capillary permeability observed physiologically after hemorrhagic shock may be explained by such alterations of endothelial zonulae occludentes.


[Thromboembolism of the lung and lower extremities in patients with chronic global congestive heart failure].

The results of a prospective study on the incidence of pulmonary thromboembolism and deep leg veins phlebitis in patients with congestive heart failure are presented. Pulmonary thromboembolism was diagnosed by means of pulmonary isotopic scanning and angiography; deep leg veins were studied using conventional and isotopic phlebography. A total incident of 60% for pulmonary thromboembolism and 92% for deep leg veins phlebitis was found, being of little significance the results suggested by clinical signs. ECG, chest X rays and laboratory tests such as arterial PO2, transaminase and lactic dehidrogenases. Among patients with pulmonary thromboembolism, the hospitalization periods were longer and more frequent, the incidence of deep leg veins phlebitis was 100%, mortality was slightly higher and the degree of hemodynamic derrangement was more advanced in patients without pulmonary thromboembolism. The rutinary use of pulmonary scanning and isotopic phlebography for detection of these complications in patients with congestive heart failure is recommended, emphasizing the need for prophylactic anticoagulant treatment in most of these patients.


[Etiopathogenic heterogeneity of mitral and aortic valve diseases. Clinico-pathological study].

This study comprises the evaluation of 120 surgically excised mitral and aortic valves, in an attempt to clearly define the nature of the underlying process. To this effect histopathological and clinical criteria were established and categorized in 4 levels of diagnostic accuracy for rheumatic fever. Ninety three percent of the mitral valves were recognized as probably or certainly rheumatic in origin, whereas only 38.4% of the aortic cases were classified in this category. Included is a discussion of the various etiopathogenic possibilities, other than rheumatic, regarding chronic valve deformities of the heart.


[Effect of hypoxia on atrio-ventricular conduction in severe respiratory insufficiency].

The role of hipoxia on A-V conduction was studied in the patients with severe respiratory insufficiency. Intervals of A-V conduction were measured under basal conditions, breathing room air and with increasing atrial rates. Results are compared with those obtained after the administration of 99% oxygen. A-V conduction times were normal in all the patients while breathing room air and in response to atrial pacing. With oxygen administration most patients had a decrease in A-V conduction at the expense of a prolonged A-H time, without significant alteration of the other time intervals. A-V conduction in chronic hipoxia with a PaO2 above 28 mm Hg is not delayed. Intranodal conduction delay with oxygen administration may be due to a decrease in sympathetic nerve stimulation.