Management of arthritis of the ankle. An alternative of arthrodesis. Twenty-eight patients treated by total ankle arthroplasty at the University of California, Irvine, were evaluated on a 100-point ankle analysis scale preoperatively and postoperatively. The average preoperative score was 35 and the average postoperative score was 74. Significant improvement occurred in function, pain relief and range of motion. The average follow-up period for these patients was 9 months. Although the number in each group is small, it does not appear that the procedure has merit for the treatment of ankle arthritis from such diverse causes as trauma, rheumatoid arthritis, aseptic necrosis of the talus and talectomy. Complications included wound healing problems in 3 patients. Malalignment of the prosthesis occurred in 2 other patients; one required revision. Ankle replacement failed in 2 patients. One patient required a fusion; the other an amputation following occlusion of the posterior tibial artery after surgery. At the present time, ankle replacement appears to be an acceptable alternative to ankle arthrodesis.


Biomechanics of the foot and ankle.

Biomechanics of the foot and ankle. The human foot evolved to provide: (1) mechanisms to limit the excursion of the center of mass during ambulation and thereby minimize the expenditure of energy; (2) a base of support of sufficien dimensions for the stability necessary to maintain the upright position without excessive muscular activity; (3) mechanisms for flexibility to absorb the shock of the body weight and for accommodation to uneven terrain; (4) rigidity of the foot when it acts as a lever in the push-off period of stance.


Triple osteotomy of the innominate bone. A procedure to accomplish coverage of the dislocated or subluxated femoral head in the older patient. The triple osteotomy of the innominate bone is a total redirectional reconstruction and is obtained by circum-acetabular osteotomies through the ilium, ischium and pubis. The method achieves coverage of a dislocated or subluxated femoral head where other iliac osteotomies are ineffective or incomplete. Triple osteotomy was performed on 175 hips including 121 congenital dislocation-subluxations. The patients' ages ranged from 6 to 35, with 70 per cent falling between 9 and 12. Eighty-six per cent had a satisfactory result. Most of the unsatisfactory results were in cerebral palsy, myelodysplasia and peroneal muscular atrophy and associated with uncontrolled muscle contractures or progressive disease.


Fractures of the hip in the institutionalized psychotic patient. A mortality and morbidity survey of 106 cases. Fractures of the hip and its resultant mortality are a reflection of age more than any other factor. The death and morbidity in this poor risk patient group with multiple medical problems can be significantly lowered by the generalized use of prophylactic antibiotics and thromboembolic protection. Stabilization of intertrochanteric fractures at the time of surgery with stronger implants, displacement osteotomy, and the judicious use of bone cement, along with primary replacement of displaced subcapital fractures allows the patient earlier ambulation before the skills of walking have been forgotten.


Slipped capital femoral epiphysis co-existent with hypothyroidism. Five patients with slipped capital femoral epiphysis were conclusively diagnosed as being hypothyroid. One was a cretin, who was diagnosed and begun on thyroid medication at four months of age but subsequently many years later developed the slip. Suspicion of hypothyroidism should exist for the clinician who finds himself with a child below age 12 with a delayed bone age, borderline mental status and a slipped capital femoral epiphysis. His attention in addition to the orthopedic management of the slip, should be directed towards laboratory studies to rule out hypothyroidism.


The use of cryosurgery in the treatment of low and medium grade chondrosarcoma. A preliminary report. Eighteen chondrosarcoma (Grade I and Grade II) have been treated with cryosurgery. One patient subsequently developed a metastasis; three later had to have an en bloc resection (in two of these there was no tumor in the specimen) and three underwent amputation (one of these had tumor in the specimen). In general, cryosurgery for low grade chondrosarcoma is encouraging as long as the limb is protected postoperatively from fracture -- using various orthopedic appliances to allow bone regeneration (i.e. ischial weight bearing brace). Other complications such as nerve paralysis have been transient. One air embolis death occurred (in another disease) where the exit of nitrogen gas was blocked. This is preventable by allowing free exit of gas from the bone. Approximately 500 cases of primary bone have been treated with cryosurgery as of this date; long term follow-up results will be reported later.


The epidemiology of femoral neck fractures in Jerusalem. A prospective study (1967-1971). A prospective study of 570 patients with fracture of the upper end of the femur was carried out between 1967 and 1971 in Jerusalem. Of three distinct ethnic groupings, Western or Ashkenazi females and Eastern or Sephardi males produced the highest incidence of fractured neck of the femur proportional to their makeup in the population at risk. No explanation for this is forthcoming as both groups are of differing sex and race. The age and sex incidence of these fractures in the Eastern and Western ethnic groups in this city showed a distinct resemblance to their geographicaly counterparts in other studies. There is an interesting seasonal pattern of incidence of fractures in females and correlation with increased physical activity during the three special holiday periods.


Dedifferentiation of low grade chondrosarcomas. In four unusual cases where a low-grade chondrosarcoma suddenly dedifferentiated into a florid, highly-malignant fibrosarcoma, the average survival was 12 months (range 5-18 months). The surgical treatment of chondrosarcoma consists of a primary excisional biopsy, and if dedifferentiation to fibrosarcoma is seen, radical excision and chemotherapy or irradiation or both.


Cystic degeneration and calcification following ischemic paralysis of the leg. Increased pressure within a closed space which leads to a compromise of the circulation and function of tissues is referred to as a compartmental syndrome. The resulting changes range from the mild reversible ones to extensive necrosis and fibrosis. Rarely, a cystic calcified mass may develop in the affected area years after the onset of ischemia. Two such cases which involve the lower limb have been reported by Gallie. The authors report one new case of late cystic degeneration and calcification following ischemic paralysis of the leg.


Posterior compartment syndrome resulting from a dissecting popliteal cyst. Case report. Calf swelling, associated with an intra-articular effusion of the knee, should be considered a dissecting popliteal cyst until proven otherwise. The posterior compartment syndrome caused by an increase in pressure within the deep posterior compartment of the leg is usually secondary to trauma. This case history of a dissecting popliteal cyst reports another unusual cause of the posterior compartment syndrome. Popliteal cysts, especially dissecting ones, are typical of connective tissue diseases, and are not limited to rheumatoid arthritis.


The intramedullary compression rod.

The intramedullary compression rod. The Kaessmann compression device was employed in 26 patients with fractures of the long bones. In 15 fractures of the tibia, prompt healing occurred, even in fractures in the distal one-fourth of the tibia. Most of these cases were treated without external plaster support, and were permitted early ambulation, with partial weight-bearing. The technique for immobilizing these fractures involves a sliding a Kuntscher nail over a tension rod, and then fixing the clevis of the tension rod to the distal bone fragments by a transverse screw. The Kuntscher nail is fixed to the proximal bone fragment by a metal lip, and after compression is achieved, a locking sleeve fixed by a screw to the tension rod, prevents loss of compression. In 11 cases of pseudarthrosis of the tibia, the medullary canal was enlarged by passing graduated drills down the bony canal, over a guide wire. The compression rod was then inserted across the pseudarthrosis, and seventy to 80 kg/cm2 pressure was applied to the bone ends. No bone grafting procedure was performed. In all 11 cases, prompt union occurred. Postoperative management was similar to that employed in the treatment of fresh fractures. Three success fusions of the ankle also attest to the effectiveness of this immobilization. Although controversy exists regarding the role of compression in the healing of fractures, the axial compression rod does overcome distraction, compresses the bony surfaces, immobilizing them securely to produce union with an economy of callus.


Acute cervical strain. Evaluation and short term prognostic factors. An independent examiner evaluated 179 consecutive private ambulatory litigant patients with soft tissue neck injuries (whiplash) from automobile injuries. Treatment of all patients consisted of neck and shoulder exercises with the exclusion of cervical collars, cervical traction and hospitalization. Forty-three patients had intermittent cervical traction in addition to the exercises. All patients were encouraged to resume their usual work and other activities. The presence of interscapular or upper back pain prognosticated a less favorable result. The average length of treatment was 7.4 weeks. Thirty-seven per cent of the patients with asymptomatic; 16 per cent showed no significant recovery. Older patients recovered as well as younger patients. There was no relation between X-ray findings of flattening or reversal of the cervical lordotic curve and the degree of recovery.


Results of single compartment arthroplasty with acrylic cement fixation. A minimum follow-up of two years. Single compartment modular knee replacements produced good or excellent three-year follow-up results in a success rate of 92 per cent. Contracture, thrombophlebitis, infections and other complications are infrequent.


The use of the Varney brace for subluxating shoulders in stroke and upper motor neuron injuries. Applying the Varney shoulder brace for painful subluxating shoulders in stroke and head injury patients with or without spasticity has proved to be an extremely effective means of reducing the subluxed shoulder. Other causes for painful shoulders in these patients must be ruled out. Not every shoulder which subluxes with or without spasticity is painful. Correct diagnosis of the etiology of the pain is essential to help the patient. Rotator cuff tendinitis, reflex sympathetic dystrophy, glenohumeral arthritis, shoulder contracture, pain due to central nervous system origin (thalmic pain) and other intrinsic causes of referred pain must be ruled out. Once the subluxed shoulder is proven to be the cause of pain, the Varney brace is an excellent orthosis for the reduction and maintenance of position. Pain usually subsides completely within 5 to 7 days.


A neurologic complication following Monteggia fracture. Posterior interosseous nerve palsy can occur following a Monteggia fracture by a variety of mechanisms. In this case report of a 35-year-old man the nerve became wrapped around an anterolaterally dislocated radial head in the course of an unsuccessful attempt as closed reduction. Cadaveric dissections demonstrated how reduction of the radial head can be blocked by an enwrapped nerve. Obviously open reduction of the fracture with exploration of the nerve is the treatment of choice.


Hemiarthroplasty for the rheumatoid shoulder joint. Hemiarthroplasty was performed in 10 patients with rheumatoid arthritis of the shoulder joint. A humeral head prosthesis was inserted to replace the articular surface of the humeral head in 12 shoulders. Marked relief of pain and improved function in long term follow-up examinations were noted in the majority of the patients. The indication for shoulder hemiarthroplasty is severe pain and chronic rheumatoid disease.


Recognition of factitial hand injuries.

Recognition of factitial hand injuries. Facitial injuries with various presentations occur with some frequency to the hand because it is a body part that is easily accessible. Methods used to produce wounds included insertion of porcupine quills, application of constrictive rubber bands, mascara injections and excoriation of healing wounds. It is important to recognize the factitial origin in order to avoid needless repetitive surgery and permanent hand disability. No specific pattern of psychopathology was found in our cases. The patients' attitude toward their lesions was one of bland unconcern and stoicism. The patients were resistant to psychiatric referral and persisted in seeking medical responsibility for cure. Successful management requires early suspicion and prompt recognition as well as establishment of non-accusatory relationship with the primary physician. Confrontation should be avoided if possible. Even if reinforced with collaborative evidence, such confrontation will have limited effect on the patient's subsequent behavior.


Airborne contamination in orthopedic surgery. Evaluation of laminar air flow system and aspiration suit. The question arises whether, on the basis of our studies, the laminar flow system and aspiration suit should be considered as useful and effective components of the overall proctocol to prevent postoperative surgical infections. Our observations do not permit a definitive answer. This would obviously depend on the demonstration of a reduction of the incidence of postoperative infection by means of a large controlled study. The infection rate encountered in this study can not be used to draw any conclusion as to the efficacy of the laminar flow systems, since there are too many uncontrollable variables which may be influential in causing a post operative wound infection. Published reports and present data seem to indicate that the airborne route of transmission is of little significance in modern surgery and that the amount of wound contamination is not necessarily a reflection of airborne contamination. Thus, the use of the laminar air flow system and aspiration suits, which are clearly designed to prevent wound infection by the airborne route, does not seem to be justified on this basis at the present time. On the other hand, the use of laminar air flow system and/or aspiration suit by necessity imposes a strict discipline in those operating rooms, where multiple personnel are routinely involved; i.e., they reduced the number of personnel in contact with patient, reduce the traffic about the surgical patient, etc., which may have significant benefits towards the control of surgical wound infections. This enforced discipline may very well account for the significant decrease in the number of positive intraoperative wound cultures in this study when laminar air flow systems and/or aspiration suits were in use.


Barton's fractures-reverse Barton's fractures. Confusing eponyms. Anterior and posterior marginal fracture dislocations of the distal radius are unusual injuries, both of which are called Barton's fracture in the current world literature. Barton's original description delineates only the posterior marginal injury. An attempt is made to clarify the nature of these injuries by a complete review of the literature and a study of the clinical experience at UCLA Hospital from 1972 through 1975. Ten anterior and five posterior marginal fractures were treated during that period of time, constituting 2.3 per cent of all distal forearm fractures. Fractures in males typically stemmed from high velocity accidents in the younger age group and were associated with significant additional injuries. The injuries in females resulted from simple falls, generally in the older age group. Eight fractures were treated open and seven closed without complications; treatment results have not been determined yet. Eponym descriptions should be discontinued and replaced with a lucid anatomically descriptive classification such as anterior and posterior marginal fracture-dislocations of the distal radius.


An unusual presentation of pigmented villonodular synovitis. A case of multiple joint and tendon involvement by PVS seems not to have been preciously reported. In a 7-year-old girl there were other organ system problems usually not seen with PVS, and the entire complex may represent a more generalized disease process. The diffuse form of the disease was refractory to multiple attempts at surgical excision. The similarities between PVS and synovial hemangioma suggest that it is important to establish the diagnosis after the first operation.


Spinal stenosis. The narrow lumbar spinal canal syndrome. This is a report of 7 cases of narrow lumbar spinal canal syndrome encountered in 7 patients in a community hospital in one year. Nerve compression occurred from pressure from enlarged posterior elements. Although the clinical manifestations were unspecific, the lumbar spine radiographs and myelographic features are quite characteristic. Supported by myelography and/or operative findings, surgical management consisted of decompression laminectomy at multiple levels, together with diskectomy at the appropriate levels. The interim results observed at one year follow-up examination were excellent.


Management of penetrating injuries of the knee. One hundred and two patients with 121 known or suspected penetrating wounds of the knee demonstrated that successful results are dependent upon early diagnosis and surgical treatment. The willingness to act immediately on the basis of clinical judgment alone is important in order to avoid irreparable damage damage to the joint. The knee should be debrided and thoroughly irrigated. The menisci, articular cartilage and bony stock should be preserved as much as possible. The joint and skin are left open. If joint surfaces are damaged or infection is grossly purulent, the synovium is also left open. The dressing is dry fluff gauze, and a Jones compression dressing which allows drainage and prevents fluid accumulation. Early active mobilization of the joint is important.


The effect of denervation on bony overgrowth after below knee amputation in rats. Bony overgrowth of amputated limbs of children is an infrequent but difficult problem. This article presents the hypothesis that the bony overgrowth is under nerve control and may represent an abortive form of partial limb regeneration. Tested in young rats, denervation produces a significant reduction in the mass and length of the bony overgrowth and a reduced rate of periosteal cell mitosis.


Measurement of regional bone and bone marrow blood flow in the rabbit using the hydrogen washout technique. This study tested the feasibility of using the hydrogen washout technique for measuring regional bone and bone marrow blood flow. Washout curves in cancellous and cortical bone were mono-exponential, indicating homogeneous perfusion of these tissues. Epiphyseal cancellous bone blood flow (0.129 +/- 0.015 ml/min/ml) and metaphyseal cancellous bone blood flow (0.170 +/- 0.014 ml/min/ml) were approximately twice as rapid as that of cortical bone (0.069 +/- 0.002 ml/min/ml). Washout of hydrogen from bone marrow was variable and usually formed a bi-exponential pattern, indicating non-homogeneous perfusion. Blood flow rate determined by analyzing the rapid components was 1.04 +/- 0.10 ml/min/ml, and that from the slow components was 0.27 +/- 0.02 ml/min/ml. Our blood flow rates are within the range of values reported by investigators using different methods, and the hydrogen washout technique offers specificity and ease of repetitive determinations not available with other methods.


Rapid recovery from contracture in rabbit hindlimb. A correlative biomechanical and biochemical study. Between 3 to 6 weeks after release of immobilized rabbits' knees, joint stiffness as determined by measurement of torque and area of hysteresis was overcome. The total hexosamine and water content of periarticular tissues had increased to within the range of control rabbits' joints and showed strong correlation with the biomechanical measurements.


Amputations of the foot and ankle. Current status. Doppler assessment of ankle and foot systolic pressure is a practical aid in the evaluation of neurocirculatory problems. If the ratio of ankle pressure to arm pressure is over 0.45, more than 90 per cent of operative procedures will heal. Intraoperative testing of blood supply aids in determining level of amputation. Healing results in 80 per cent of cases if bleeding occurs in the skin within three minutes after release of tourniquet. With vigorous debridement of infected soft tissue and bone, the remaining tissue will often heal in local foot operations. A high percentage of patients with neuro-circulation disorders become bilateral amputees. Partial foot and Syme level amputations allow these patients to remain prosthetic users. Function tests show the Syme amputee to be superior in stride length, velocity, cadence and oxygen uptake when compared with the below-knee and above-knee amputees. The criteria of McKittrick must be followed carefully to ensure healing of transmetartarsal amputations.


The management of spastic deformities of the foot and ankle. The most common ankle and foot deformities in cerebral palsy are equinus, equinovalgus, equinovarus, calcaneus and hallux valgus. It makes little difference how the length of the triceps surae is re-established and how its stretch reflex is weakened as long as the patient is carefully chosen, the procedure done well and the postoperative regimen prolonged and detailed. The most common cause of failure is inadequate use of night support during growth to prevent recurrence. Significant equinovalgus has been successfully managed by heel cord lengthening and subtalar arthrodesis. The arthrodesis should not be performed unless the equinus has been corrected prior to or at the same time as the procedure to correct the valgus. Overcorrection must be avoided. Where equinovarus needs surgical correction and no bone deformity exists, heel cord and posterior tibial lengthening are successful. If there is significant bone deformity, a triple arthrodesis may also be necessary when growth is complete. The latter procedure should not be used to correct equinus for it ends up with a foot short in height, length and width.


Children who age rapidly--progeroid syndromes: case report of a new variant. A case report of an apparently unique progeroid syndrome is reported here. Major clinical characteristics included growth failure with onset of senility in the early teens, atrophic skin, hypogonadism, and retinal and vascular sclerosis. Mental retardation was present, but could have been attributable to trauma. The replicative life spans of several lines of cultured skin fibroblasts were within the normal range, in contrast to the limited life-spans of such cultures from patients with Werner's syndrome, whom our patient most closely resembles. Also, in contrast to Werner's syndrome, our patient did not have white or gray hair or cataracts.


Rigid flatfoot.

Rigid flatfoot. The proper management of the rigid flat-foot requires an accurate diagnosis since the condition is treated on causal or rational basis. Calcaneonavicular coalition best seen on an oblique view of the foot may be treated by resection of the coalition with extensor digitorum brevis interposition. If the diagnosis is made sufficiently early, the resection can lead to an essentially normal foot. Coalition between the talus and the calcaneus may occur in the posterior, middle or anterior facet. The most common coalitions are seen in the middle facet area followed by those in the anterior facet with the posterior facet coalition rarely being seen. Coalitions in the area of the middle facet are usually managed nonoperatively; triple arthrodesis is used only if symptoms are not relieved by nonoperative measures. Resection of a talocalcaneal coalition in the middle facet is rarely indicated but occasionally will give relief when the coalition either presses on the medial plantar nerve or causes a mechanical disturbance of the ankle. Anterior facet coalitions should receive a trial of cast immobilization but frequently require triple arthrodesis. Other conditions such as rheumatoid and post-traumatic arthritis will frequently respond to a period of immobilization in a plaster cast. Triple arthrodesis has not been required in rheumatoid arthritis in the author's series but occasionally is necessary in the post-traumatic rigid flatfoot. Other rare causes of the rigid flatfoot should be kept in mind for a complete diagnostic evaluation since even a neoplasm (fibrosarcoma) has been reported to cause this symptom complex.


Preschool developmental testing in prediction of school problems. Studies of 55 children in Denver. Sixty-five children from lower income families, first evaluated with the Denver Developmental Screening Test (DDST) and the Stanford-Binet Intelligence Scale at age 4 to 6 years, were followed up 3 years later to determine how well preschool test results could predict later school problems. Eighty-eight per cent of children with Abnormal DDSTs, 66% of children with Questionable DDSTs, and 32% of children with Normal DDSTs showed later school problems. Combining DDST and IQ results did not change the total number of children who would be misclassified, but the type of misclassification changed. When developmental screening is used to identify children at risk for developing school problems, children with Questionable  findings should be referred for further evaluation along with those with Abnormal findings since a high percentage of Questionables develop school problems despite adequate intelligence.


Vietnamese and Cambodian orphans 1975--the first look. The initial medical screening and treatment at Clark Air Force Base. In April of 1975, the United States government evacuated approximately 2,000 orphans from Vietnam and Cambodia. More than 1,500 orphans received initial medical evaluation and treatment at Clark Air Force Base, Republic of the Phillipines. The orphans underwent a minimum of 2 physician evaluations and were individually cared for by a volunteer. One hundred and six children were ill enough to require acute admission to the hospital. Four infants died while at Clark. No unusual tropical illnesses were diagnosed at Clark nor were any diseases identified that might represent a significant health hazard to the United States. The medical conditions found among these orphans appear to be similar to the problems found among the children of migrant farm workers in the United States.


Neurology of hard times. Economic depression as related to neurologic illness in children. Many children and their families have experienced "hard times" because of the current economic conditions. Five cases are presented in which neurologic illness in children was related to changes in the family's economic circumstances. Pediatricians are encouraged to look carefully at the impact of changing economic conditions upon child health.


Studies on digitalis. VIII. Digitoxin metabolism on a maintenance regimen and after a single dose. The metabolic pattern of cardioactive and inactive conjugated metabolites of digitoxin on maintenance (9 patients) and after a single 0.6-mg dose (5 patients) was studied in patients with normal renal and hepatic function. Serum samples were obtained 24 hr after the last dose, and urine was collected over 24 hr. The extent of conjugation to glucuronic and sulfuric acid was 35.0% (SD, 17.4) in whole serum and 31.6% (SD, 19.3) in urine samples. Unchanged digitoxin was the main cardioactive substance found both in serum and in urine (89.7% and 87.0%) in the steady-state group. All known cardioactive metabolites were present; digoxin represented less than 1%. All active metabolites were conjugated to glucuronic/sulfuric acid. Serum and urine patterns of metabolites were quite similar, Hydrolysis and conjugation appeared to be more important pathways than hydroxylation. Unchanged digitoxin was the most important cardioactive substance in serum and urine (80.4% and 56.5%) in the single-dose group. Digoxin was the main cardioactive metabolite (12.5% in serum and 25.5% in urine). All active metabolites were conjugated. Hydroxylation, hydrolysis, and conjugation seemed to be equally important. The most important differences between the steady-state and single-dose groups were that in the steady-state group there was significantly more unchanged digitoxin, far less digoxin, and less hydroxylated metabolities than in the single-dose group. Caution is thus necessary when interpreting single-dose data for a drug that is used for maintenance.


Conservative management of pes valgus with plantar flexed talus, flexible. The type of flat foot that we have called pes valgus with plantar flexed talus, flexible, was treated in children with the Helfet heel seat or the UCBL shoe insert. In follow-up examination of 71 cases for periods longer than one year, 79 per cent of the patients showed that the UCBL shoe insert and the Helfet heel seat improved the clinical and roentgenographic appearance of the foot. The Helfet heel seat is recommended in cases where the plantar flexion angle of the talus is 35 to 45 degrees and the UCBL shoe insert in those cases of plantar flexion of the talus greater than 45 degrees.


Depression of renal clearance of furosemide in man by azotemia. The renal clearance of furosemide and tetraethylammonium (TEA) were compared in 10 patients with hypertensive nephropathy. BUN and creatinine ranges were 10 to 88 mg/dl and 0.9 to 3.8 mg/dl, respectively. Diuretics were discontinued 48 hr prior to the study, and 2 consecutive clearances (ml/min/1.73 m2BSA) of creatinine were performed. The patient then received a bolus followed by a constant infusion of furosemide-14C and tetraethylammonium-14C (analyzed by specific methodology for plasma and urine), both in subpharmacologic doses. After 40-min equilibration sequential 20-min clearance periods were obtained. Both the clearance of furosemide (range 17 to 133) and TEA (range 99 to 443) correlated negatively with BUN and serum creatinine and positively with creatinine and urea clearances. Thus, by using a constant-infusion technique we demonstrated that the renal clearance of furosemide is depressed by azotemia in man and that there was greater depression with furosemide than with TEA.


The operative treatment of hypermobile flatfeet in the young child. Osteotomy of the anterolateral aspect of the calcaneus in 81 hypermobile flatfeet produced a good or excellent clinical result in 95 per cent of the feet. Roentgenographically, 72.8 per cent of the feet have normal alignment and normal joint spaces, 5 per cent have narrow subtalar joints, and 22.2 percent have narrowing of the talonavicular joint. Arthrosis of the talonavicular joint can be demonstrated preoperatively by routine roentgenograms and probably develops as a result of excessive load on this joint by the flatfoot position. It is frequently associated with loss of foot motion postoperatively but is usually not accompanied by foot pain. There is no relationship between preoperative pain in the foot and arthrosis of the talonavicular joint.


Clinical effects and pharmacokinetics of racemic methadone and its optical isomers. The respiratory and pupillary effects of oral l-, d-, and d,l-methadone were studied in healthy male volunteers 21 to 35 yr of age. The mean half-life of drug in blood was 22 hr for racemic methadone, 24 hr for l-methadone, and 25 hr for d-methadone. The effects of d-methadone were not significantly different from the placebo response at a 7.5 mg dose, whereas a 50 and 100 mg dose slightly depressed respiration in one subject each. Both 7.5 mg of l-methadone and 15 mg of d,l-methadone induced intense and sustained respiratory depression and miosis. The changes induced by l-methadone were of longer duration than those of d,l-methadone, lasting more than 72 hr in some subjects. Whole blood drug concentration correlated well with respiratory depression and miosis for l- and d,,l-methadone. The potency ratio of l-methadone to d,l-methdone, calculated from blood drug concentration data, was found to be 3.0 for respiratory depression and 2.7 for miosis. The antiduretic effect of 15 mg of d,l-methadone was investigated in three subjects and was found to persist for as long as measurements were taken, namely 11 and 12 hr in two subjects. d,l-Methadone administered frequently for pain may have cumulative effects on respiratory control and ability to excrete a water load.


Comparative metabolism of benzo[a]pyrene and drugs in human liver. The oxidative metabolism of antipyrine, hexobarbital, coumarin, zoxazolamine, 7-ethoxycoumarin, and the chemical carcinogen benzo[a]pyrene (BP) was studied in 32 adult human livers obtained at autopsy. When enzyme activity for one substrate was plotted against enzyme activity for a second substrate for each of the 32 livers, statistically significant correlations were found between the rates of metabolism of BP and the rates of metabolism of each of the other five drug substrates. The degree of correlation was dependent upon the substrate pair that was studied. Highly significant statistical correlations (p less than 0.001) for monooxygenase activities among the different livers were observed for BP with antipyrine (r = 0.85), antipyrine with zoxazolamine (r = 0.82), antipyrine with hexobarbital (r = 0.79), zoxazolamine with 7-ethoxycoumarin (r = 0.75), antipyrine with coumarin ( r= 0.72), zoxazolamine with coumarin (r = 0.72), BP with hexobarbital (r = 0.72), hexobarbital with coumarin (r = 0.71), BP with zoxazolamine (r = 0.69), hexobarbital with zoxazolamine (r = 0.64), coumarin with 7-ethoxycoumarin (r = 0.61), and BP with coumarin (r = 0.57). Less significant correlations were obtained for BP with 7-ethoxycoumarin (r = 0.35; p = 0.05). It is not known whether the relationships between the metabolism of the several substrates described here for autopsy livers would also occur with fresh livers. The lack of a perfect correlation for any of the substrate pairs suggests the presence in human liver of multiple monooxygenase enzyme systems for the metabolism of benzo[a]pyrene and the five other substrates studied, as well as heterogeneity in their distribution among the 32 livers that were examined. The approach described in the present report may have significance in the study of the comparative metabolism of drugs, chemical carcinogens, and other environmental pollutants by human tissues and may help us find predictor drugs that will be useful for evaluating the drug- and carcinogen-metabolizing capacity of different individuals in the human population.


Acetaminophen production in man after coadministration of acetanilid and phenacetin. A study with stable isotopes. A new method for the investigation of interindividual differences in drug metabolism is described. We have studied the metabolism of ring-deuterated acetanilid in man following the coadministration of phenacetin. The principal metabolite of acetanilid-d5 is acetaminophen-d4, and the principal metabolite of phenacetin is acetaminophen-do. Using a gas chromatograph--mass spectrometer (gc-ms) we are able to monitor both the devterion-labeled acetaminophen produced by hydroxylation of acetanilid-d5 and the nonlabeled material produced by oxidative removal of the ethyl group in phenacetin. This system allows us to detect differences in the handling of these drugs by different subjects. nonlabeled material produced by oxidative removal of the ethyl group in phenacetin. This system allows us to detect differences in the handling of these drugs by different subjects.


Plasma pyridostigmine levels in patients with myasthenia gravis. Plasma concentrations of pyridostigmine were measured in 7 patients with myasthenia gravis. Six subjects on oral pyridostigmine bromide were stabilized on widely different doses of the drug (60 to 660 mg/day). Nevertheless, the concentration of the quaternary amine in plasma was maintained within a relatively narrow range (usually between 20 and 60 ng/ml). In 3 myasthenic patients, the area under the plasma concentration-time curve was relatively constant for 4 hr after the same oral dose of pyridostigmine (60 mg). Despite this similarity, there were in general considerable interindividual differences in the bioavailability of pyridostigmine in myasthenic patients. In 1 subject, the bioavailability of the quaternary amine was increased sixfold by doubling the oral dose from 30 mg to 60 mg. After oral administration of pyridostigmine, the half-life of the drug in one subject (4.25 hr) was almost three times as great as after intramuscular administration in a different patient (1.49 hr).


Initial clinical trial based on biochemical methodology of zimelidine (a serotonin uptake inhibitor) in depressed patients. The bicyclic compound Z-1-(4-bromophenyl)-1-(3-pyridyl)-3-dimethylaminopropen (zimelidine) has a pronounced inhibitory effect on neuronal 5-hydroxytryptamine (5-HT) uptake in animals. Zimelidine was given to 6 depressed patients in doses ranging between 25 and 150 mg twice daily for about 3 wk. To get an objective assessment of its pharmacologic effects, the following variables were monitored: (1) plasma levels of parent compound and its desmethylated metabolite; (2) the 5-HT and norepinephrine (NE) uptake inhibiting activity in vitro of plasma drawn from the patients; and (3) the concentrations of the main metabolites of serotonin (5-HT), tryptamine, NE, and dopamine in cerebrospinal fluid (CSF), i.e., 5-hydroxyindoleacetic acid (5-HIAA), indoleacetic acid (IAA), 4-hydroxy-3-methoxyphenylglycol (HMPG), and homovanillic acid (HVA), respectively. Plasma from the patients markedly inhibited 5-HT uptake compared to NE uptake. The inhibitory effect of 5-HT uptake and the plasma concentration of the desmethylated metabolite correlated significantly. The 5-HIAA levels in CSF decreased markedly in 4 patients while the IAA levels increased. The levels of HMPG also decreased significantly, but less so than the 5-HIAA levels. The effects on HVA were inconsistent. Zimelidine appears to be a selective inhibitor of 5-HT uptake in central monoamine neurons and is therefore an interesting pharmacologic tool in future central nervous system (CNS) research.


Hemolytic potential of methocarbamol.

Hemolytic potential of methocarbamol. Methocarbamol, a compound related to mephenesin, has in vitro hemolytic potential. A study was performed to determine whether any hemolysis was detectable after intravenous injection. Methocarbamol and its vehicle (50% polyethylene glycol-300) was compared with vehicle alone and with normal saline controls in high- and low-dose regimens in normal volunteers. Significant increases in plasma hemoglobin were detected 30 min after intravenous injection of methocarbamol or its vehicle alone. Maximum initial plasma hemoglobin levels were approximately 10 mg/dl with vehicle alone, but only 4 mg/dl with the methocarbamol added. Serum haptoglobin levels fell after both high-dose methocarbamol and vehicle during the 3-day period of treatment. Hemolysis, though detectable, did not exceed levels found under physiologic circumstances such as exercise, and represents only a small fraction of the normal daily hemolysis of aged erythrocytes.


Salivary and urinary lithium clearance while recumbent and upright. Excretion of lithium in urine and saliva was studied in healthy males while recumbent and while upright, walking and standing quietly. An oral dose of 24.3 mEq of LI+ was taken as three lithium carbonate tablets 13 hr before clearance tests. Urinary lithium clearance decreased when posture was changed from recumbent to upright, but salivary lithium clearance was not affected by the abrupt change in posture. A correlation was observed while recumbent between lithium clearance in urine and saliva, but not while upright. The findings are related to the extrapolation of saliva lithium excretion data to urinary lithium clearance.


On the question of an interaction between sulindac and tolbutamide in the control of diabetes. The effect of sulindac and tolbutamide on the control of diabetes was studied in 12 tolbutamide-treated maturity-onset diabetics with stable glycemic control. After one week of hospitalization on a metabolic ward for adjustment of diet and activity, the patients were treated with sulindac, 200 mg twice daily for one week. The time-to-peak plasma tolbutamide concentration was 3.1, 3.1, and 3.2 hr, respectively, after tolbutamide alone, after the first dose of sulindac, and after sulindac for a week. The areas under the plasma tolbutamide curve were 23.68, 22.10, and 22.78 for the same periods. The half-life for plasma tolbutamide was 7.46, 7.15, and 7.38 hr, respectively. None of the differences were statistically significant. The mean fasting plasma sugar was lower after the sulindac treatment (from 12.5 to 112.9 mg/100 ml, p less than 0.05), but the postprandial values increased slightly (from 137.7 to 142.6). It was concluded that there was no clinically significant interaction between sulindac and tolbutamide.


Toward the operational identification of adverse drug reactions. The evaluation of adverse drug reactions in clinical practice is somewhat arbitrary and is characterized by considerable differences of opinion. This report presents a decision table algorithm approach toward the development of an operational system for the identification of adverse drug reactions. The algorithm incorporates an estimate of the certainty of the link between the untoward clinical event and the suspect drug, and examines the underlying causes of the identified drug reactions. Use of such a system is a first step toward reducing ambiguity in the evaluation of adverse drug reactions.


Studies on digitalis. IX. Some kinetic aspects of digitoxin metabolism. The metabolic pattern of cardioactive and inactive conjugated metabolites (a maximum of 24 substances) was studied in one female and one male after a single dose of 0.6 mg digitoxin intravenously. Serum samples were obtained after 24 hr, and 24-hr urine was collected after 1, 2, 4, 6, and 8 days. With the methods used, enzymatic cleavage of conjugated bonds, thin-layer chromatography (TLC) separation, and a modified 86Rb method, the products of hydroxylation, hydrolysis, and conjugation could be separated. The Kendall rank correlation coefficient was used to compare the results from Subjects 1 and 2. Conjugation was the most rapid process, followed by hydrolysis and hydroxylation. Metabolism was progressive, leading to an increase in metabolites resulting from several enzymatic processes with time. Unchanged digitoxin reached minimum values on the fourth and sixth days and increased again on the eighth day. This indicated a continuous release of digitoxin from tissue stores and the enterohepatic circulation.


Differences between the effects of practolol and propranolol on the diastolic properties of the left ventricle. To elucidate the mechanism by which left ventricular and diastolic pressure (LVEDP) is reduced by practolol, ventricular volumes, hemodynamics, and diastolic elastic stiffness were determined before and 10 min after intravenous practolol (400 mug/kg) in 12 patients. Heart rate decreased in all patients after practolol (avg., --9/min, p less than 0.02). There was an insignificant increase in stroke work index and decrease in cardiac index attributable to the fall in rate. Practolol did not change and diastolic volume or ejection fraction, but the average LVEDP fell from 21 to 15 mm Hg (p less than 0.01) which was sustained even with atrial pacing to prepractolol heart rates. Diastolic elastic stiffness was also reduced after practolol (0.665 to 0.593, p less than 0.0025). The data indicate that practolol exerts a negative chronotropic effect on the intact heart and, in contrast to other beta blockers such as propranolol, appears to decrease diastolic stiffness in the left ventricle.


Frequency distribution of free warfarin and free phenytoin fraction values in serum of healthy human adults. The protein binding of racemic warfarin was determined in serum from 57 normal adults (27 men and 30 women). The free fraction of warfarin (total concentration, 0.8 mug/ml) ranged from 0.0050 to 0.0186 and was log-normally distributed. The frequency distribution differs from that in rats in which the serum free fraction values of warfarin are trimodally distributed. The protein binding of phenytoin was determined in serum from 39 of the subjects. The free fraction of phenytoin (total concentration, 15 mug/ml) ranged from 0.111 to 0.155 and was unimodally distributed. There was no apparent correlation between the extent of protein binding of warfarin and phenytoin in individual serum samples. The pronounced intersubject variation in serum free fraction of warfarin observed in consistent with our previous finding that serum protein binding is an important determinant of interindividual differences in the total clearance of warfarin in man. On the other hand, the relatively narrow distribution of free phenytoin fraction values suggests that differences in serum protein binding of phenytoin are not an important cause of the prounounced interindividual differences in the total clearance of phenytoin by subjects with normal renal function.


Individualization of phenytoin dosage regimens. Two methods for arriving at optimum, individual phenytoin dosage regimens have been evaluated in 12 patients. (1) Individual Michaelis-Menten pharmacokinetic parameters for phenytoin were estimated from two reliable steady-state phenytoin serum concentrations resulting from different daily doses: The observed steady-state phenytoin serum levels obtained after 3 to 8 wk of compliance with dosage regimens calculated from the individual pharmacokinetic parameters agreed well with predicted levels (r = 0.824, p less than 0.02). The average deviation between observed and predicted levels was 0.04 mug/ml (range, +/- 3.2 mug/ml). (2) A previously published nomogram for making adjustments in phenytoin dosage regimens: The serum phenytoin concentration actually expected from the dose indicated by the nomogram was calculated using individual pharmacokinetic parameters. The daily dose for one patient would have exceeded his estimated maximal rate of metabolism. The correlation between calculated and predicted phenytoin serum levels in the other 11 patients was weak but significant (r= 0.360, p less than 0.05). The average deviation was --3 mug/ml (range, 3.9 to --11.3 mug/ml). It was concluded that the use of individual pharmacokinetic parameters is practical and is also superior to the nomogram.


Plasma concentrations of 5-(4-hydroxyphenyl)-5-phenylhydantoin in phenytoin-treated patients. A mass fragmentographic method was used to determine unconjugated and conjugated 5-(4-hydroxyphenyl)-5-phenylhydantonin (4-OH-DPH) in plasma of patients being treated with phenytoin (DPH). The plasma concentration of unconjugated 4-OH-DPH is stable at steady-state for DPH and the level does not change during the dose interval. Most patients (82.5%) have plasma concentrations of unconjugated 4-OH-DPH between 0.04 and 0.2 mug/ml at concentrations of DPH between 5 and 30 mug/ml. Interindividual differences in the ratio between plasma concentration of unconjugated 4-OH-DPH and DPH were noted in a wide range of doses. Dosage adjustments of DPH in patients were not associated with major changes in the plasma level of unconjugated 4-OH-DPH. The plasma concentration of conjugated 4-OH-DPH also showed interindividual differences and varied between 1.2 and 4.5 mug/ml in patients with DPH concentrations between 5 and 30 mug/ml. The data are consistent with the concept of Michaelis-Menten kinetics for DPH metabolism.


Influence of acute viral hepatitis on disposition and plasma binding of tolbutamide. To study the influence of acute hepatic disease on the disposition of tolbutamide, we measured tolbutamide plasma protein binding and pharmacokinetic parameters after intravenous administration of the drug to 5 subjects during and after apparent recovery from acute viral hepatitis. Although during the acute phase of illness protein binding of the drug decreased in all, volume of distribution of tolbutamide (0.15 +/- 0.03 L/kg) did not change. Clearance based on total concentration of tolbutamide in plasma increased in all subjects during the acute phase of study (26 +/- 5.4 ml/hr/kg) in comparison to the recovery phase (18 +/- 2.8 ml/hr/kg, p less than 0.02). Protein binding decreased after unconjugated bilirubin was added to plasma from the recovery phase, but not to the extent observed during the acute phase of illness at comparable levels of bilirubin. Clearance based on unbound drug concentration, calculated by dividing the observed plasma clearance by the fraction of unbound drug in plasma, did not differ significantly between the 2 study phases (300 +/- 47 and 260 +/- 39 ml/hr/kg). These observations suggest that the increase in clearance based on total drug concentration in plasma during hepatitis can be attributed solely to decreased plasma binding. This decrease in binding may be attributed in part, but not entirely, to increased combination of bilirubin during illness. The concentration of unbound drug in plasma at steady-state is determined by the rate of drug administration and the clearance based on unbound drug. If this clearance does not change during hepatic disease, no dosage alterations for tolbutamide and other comparable drugs are necessary to maintain a constant concentration of unbound drug.


Theophylline kinetics in acute pulmonary edema. Nine patients with acute cardiogenic pulmonary edema were given theophylline intravenously, and its disposition was observed over the next 24 hr. Compared to that in 19 normal subjects, these patients had prolonged plasma half-lifes (mean, 22.9 from 6.7 hr) and decreased plasma clearances of theophylline (mean, 0.041 from 0.062 L [kg-1] hr-1). The intersubject variation in these parameters was 20-fold in patients with pulmonary edema and 4-fold in normal subjects. Since the peak plasma concentrations attained and the apparent volumes of distribution were not different in the two groups, a suitable initial dose can be calculated. A loading dose of 4.5 to 5 mg/kg theophylline (6 mg/kg aminophylline) given over 20 min appears safe. Because of the great variability in the plasma clearance of this drug in patients with heart failure, plasma concentrations and toxicity would be unpredictable after repeated doses or constant infusions.


Control of clofibrate toxicity in uremic hypertriglyceridemia. A daily dose of 1.5 to 2.0 gm of clofibrate lowers serum triglyceride (TG) levels in patients with normal renal function but causes muscle toxicity and elevated creatine phosphokinase (CPK) levels in patients with long-term renal failure. Plasma clofibrate disappearance is prolonged as much as seven times normal in severely uremic patients. A marked reduction in the standard 14 gm/wk clofibrate dose to a total dose of 1.0 to 1.5 gm/wk effectively lowered serum TG levels (--28%, p less than 0.02) in hypertriglyceridemic hemodialysis patients without toxicity. The serum clofibrate level at this dose was comparable to that in hypertriglyceridemic nonuremic patients receiving 14 gm/wk of clofibrate. The dose of clofibrate administered to hemodialysis patients can be adjusted to avoid toxicity and provide the desired therapeutic effect by monitoring serum CPK and TG levels.


Prolonged delta-9-tetrahydrocannabinol ingestion. Effects of sympathomimetic amines and autonomic blockades. In order to evaluate the possible effects of delta-9-tetrahydrocannabinol (THC) on autonomic nervous system function, cardiovascular responses to intravenous isoproterenol, phenylephrine, atropine, and propranolol were compared in hospitalized volunteers before and after 14 days of THC ingestion. There was no significant alteration in responses to isoproterenol or phenylephrine, although in one subject the pressor effect of phenylephrine was considerably augmented by THC. Heart rates after parasympathetic (atropine) blockade and after combined parasympathetic and sympathetic (propranolol) blockade were significantly greater during THC ingestion. These and other data presented are consistent with the picture of reduced sympathetic and enhanced parasympathetic activity described in animals on THC. During THC ingestion, atropine had a pronounced pressor effect, which might represent a clinically significant drug interaction.


Aging and ethanol metabolism.

Aging and ethanol metabolism. The effect of aging on the distribution and elimination of ethanol was studied in a group of 50 healthy subjects ranging in age from 21 to 81 yr (mean, 53.3). Ethanol was administered in a continuous 1-hr infusion at a mean rate of 375 mg/m2 body surface area/min (equivalent to a mean dose of 0.57 gm/kg body weight). Serial blood samples for the determination of ethanol concentration was obtained at 15- to 30-min intervals for up to 4 hr post infusion. Ethanol elimination and distribution were evaluated with the aid of a two-compartment model. Rates of ethanol elimination were not affected by age. Peak ethanol concentration in blood water at the end of the infusion period was correlated with age (r= 0.55, p less than 0.001). Lean body mass and total volume of distirbution fo the ethanol were negatively correlated with age. The smaller volume of distirbution, in association with the decreased lean body mass, most likely explains the higher peak ethanol concentration found in the blood after administration of an ethanol does on the basis of surface area in the old as compared with the young subjects. This study demonstrates that age-related changes in body composition are important factors in the study of ethanol metabolism and its pharmacologic effects.


Kinetic model for gentamicin dosing with the use of individual patient parameters. Multiple-infusion dosing regimens for gentamicin were established for 84 patients with the use of individually calculated values of elimination kinetic parameters. Serum level-time data obtained after a single infusion were used to determine the patient's gentamicin half-life (t 1/2) and distribution volume. Patients with serum creatinine (Cr) less than 1.2 mg per 100 ml had t 1/2 (mean, 2.25 hr) and total body clearances (mean, 0.082 L/hr/kg) significantly different from those with Cr greater than or equal to 1.2 mg/100 ml (means, 5.3 and 0.039, respectively). Distribution volumes were not significantly different (means, 0.22 and 0.21 L/kg, respectively). Calculations of dosing intervals and infusion rates, based on each patient's kinetic parameters and desired steady-state peaks and nadirs, assumed a one-compartment model with first-order elimination and 1-hr constant-rate input at fixed intervals. Follow-up steady-state peak and nadir levels were measured in 63 of the regimens. Differences between predicted and measured peak levels averaged --0.05 mug/ml with 60% of the measured values falling within 1 mug/ml of that predicted. Predicted-measured nadir differences averaged --0.62 mug/ml (significantly different from zero) indicating slight bias in the model. Fifty-six percent of these nadirs were within 1 mug/ml of that predicted.


Sequelae of abdominal radiation and their medical management. As various chemotherapeutic agents are added to treatment routines, the possibility of adverse effects is appreciably increased, particularly in those organs for which the agents have specific toxicity. Symptoms most commonly associated with radiation sickness, such as malaise, anorexia, nausea, vomiting, diarrhea, dysphagia, dermatitis, and depleted hemopoietic elements, are usually seen late in the course of radiation therapy or shortly thereafter. Consequently, they are managed by the physician in charge of radiation or the patient's referring physician. The general physician may be concerned with symptoms arising from delayed organ pathology. These symptoms may arise in many tissues that are still considered somewhat radioresistant, but secondary to sequelae arising because of connective tissue changes from obliterative narrowing of the finer vasculature. Radiation may be only one of several possible causes, and the symptoms of sequelae may appear only after a long latent period, so that the previous radiation may not be considered in the differential diagnosis unless a detailed history is taken. The medical management of these sequelae is, in general, similar to that used for the pathology produced in these organs by other agents.


Management of neonatal seizures.

Management of neonatal seizures. Seizures in the neonatal period are usually concomitants of serious neurological disease. The convulsive phenomena take certain distinctive and often subtle forms because of the status of the neuroanatomical and neurophysiological development of the neonatal brain. The predominant etiological process is hypoxic-ischemic encephalopathy, but intracranial hemorrhage, intracranial infection, development defects and metabolic disorders are also responsible for a considerable proportion of cases. Prognosis is related primarily to the neurological disease that underlies the seizures. Treatment may be specific for the underlying disorder, e.g., glucose, calcium, magnesium, pyridoxine, but whatever the cause, urgent control of the convulsions is important because they may have deleterious consequences. Phenobarbital is the single, most important anticonvulsant in the management of neonatal seizures.


Neonatal hypocalcemia mechanism of occurrence and management. Early neonatal hypocalcemia occurs in premature infants, infants with birth asphyxia, and infants of diabetic mothers. Etiological considerations include decreased calcium (Ca) supply, increased endogenous phosphate load, hypomagnesemia, alkali therapy, functional hypoparathyroidism, defects in vitamin D metabolism, and possibly calcitonin excess. Late neonatal hypocalcemia occurs, with malabsorption of magnesium (Mg), increased exogenous phosphate loading, after alkali therapy of diarrheal acidosis, hypoparathyroidism, and vitamin D related disorders. The therapy of hypocalcemia includes oral or iv Ca salts and in the near future, possibly the newly discovered vitamin D metabolites.


Psychodynamic considerations in the neonatal ICU. A description of the psychodynamic patterns of behavior among the Neonatal Intensive Care Unit staff, the parents, and the neonate is presented by a consulting child psychiatrist, who has spent three and one-half years working in an NICU. This is a clinical and empirical study that relied on informal and unstructured interviews with the staff and the parents, the short-term and long-term observations of their behavior, and the personal objective and subjective analysis of the psychiatrist. From this has emerged a picture of a dynamic that recreates the nuclear family within the confines of the NICU from the nurses and the physicians. These surrogate mothers and fathers play out unconscious parental roles with the neonate and with each other. Given this setting, inappropriate maternal attachment can occur between primary nurse and her charge, as well as inappropriate paternal attachment occurring between physician and infants under his medical care. Understanding of these psychodynamic reactions is basic to implement parental involvement in the NICU, so as to encourage the natural infant-parent bonding.


Perilesional vitiligo in melanoma.

Perilesional vitiligo in melanoma. The malignant transformation of a plantar nevus is presented. Perilesional vitiligo developed concurrently with the onset of malignancy. The primary lesion was controlled surgically, but the patient succumbed to metastiatic melanoma within a year. The relation of perilesional vitiligo in malignant melanoma to the so-called halo nevus, and the immunologic significance of these discolorations is reviewed.


Pearly penile papules: incidence.

Pearly penile papules: incidence. Eight hundred forty consecutive male patients were examined for the presence of pearly penile papules. The age, race and presence or absence of circumcision were recorded. Two hundred fifty-three (30.1%) of patients had lesions, and there was a significantly increased incidence of pearly penile papules in Negroes and uncircumcised men. A significantly greater proportion of Negroes were uncircumcised, possibly explaining the racial difference. The incidence of papules was greatest in young adults and tended to decrease with increasing age. A higher percentage of men over 40 had pearly penile papules than previously reported.


Myiasis Dermatobia hominis, Linn: report of a case and review of the literature. A description of the life cycle of the tropical botfly, Dermatobia hominis, is presented. The entomology of this parasite is discussed along  with the pathologic manifestations of human infestation and a description of the various modes of treatment. A recent case of multiple botfly infestation in a young man during a trip to Central America is reported. A review of the literature including the earliest reported case (1904) is presented, along with a brief discussion of the epidemiology and public health aspects of this problem.


Hypomelanotic canopy of sarcoidosis.

Hypomelanotic canopy of sarcoidosis. A case of cutaneous hypopigmented macules localized above deep dermal and subcutaneous sarcoid granulomas in a patient with systemic sarcoidosis is presented. Melanin was only sparsely distributed in the upper stratum malpighii. Hypopigmentation is an unusual manifestation of sarcoidosis. With an armamentarium of clinical observation, dermatologists may suspect a hypomelanotic cutaneous diadem overlying a palpable dermal mass to be a visual vignette of a sarcoidal montage requiring diagnostic biopsy.


Subungual exostosis.

Subungual exostosis. This report is intended to focus attention on the often occurring, but seldom reported, subungual exostosis. Familiarity with its clinical characteristics should enable the physician to make a preoperative diagnosis or at least include it in the differential diagnosis of any subungual growth. Establishing the practice of x-raying all subungual tumors may save the physician's ego from the trauma of a missed diagnosis. More importantly, however, it may save the patient from unnecessary and at times even unnecessarily drastic surgery.


Dermatomyositis and Malignancy.

Dermatomyositis and Malignancy. Dermatomyositis is a disease of unknown etiology characterized by muscle weakness and associated with a variety of cutaneous lesions. There appears to be an increased incidence of malignancy among patients with dermatomyositis. The association is estimated at about 20 percent.


Bowen's Disease of the Finger.

Bowen's Disease of the Finger. Four cases of Bowen's disease of the finger have been treated, three during the past two years. This form of carcinoma-in-situ should be considered in the differential diagnosis of any persistent scaly and/or crusted lesion of the finger. Bowen's disease in this particular site may be more common than the literature suggests.


Treatment of cancer of the eyelids.

Treatment of cancer of the eyelids. With a few modifications, the old technique of curettage and electrodesiccation has been successfully applied to the treatment of eyelid cancer.


Facial osteoma.

Facial osteoma. Osteoma cutis is an oddity--small blue spots appearing de novo, unconnected to any other disease or syndrome. To briefly quote: "The appearance of a cell or tissue where it is normally absent excites curiosity and stimulates speculation as to its origin. Heterotopic bone deposition in the skin is such a phenomenon. Extrinsic bone formation is either neoplastic or metaplastic. This presentation represents neoplasia. The term osteoma is restricted to lesions with primary bone formation."25 I would welcome suggestions on therapy other than chelation, which is patently inappropriate, and strip mining, which has already been tediously tired.


The significance and prognosis of chronic bifascicular block. The clinical course of 303 patients with bifascicular block was reviewed. Initially, 62% of the total group had evidence of heart disease. The highest frequency of heart disease was in patients with left bundle-branch block and first-degree atrioventricular block (78% or 22/28), while the lowest was in those with right bundle-branch block and left axis deviation (56% or 55/98). During the subsequent clinical course the occurrence of cardiovascular morbidity was greatest in patients who had left bundle-branch block and heart disease (55% or 49/89). Complete heart block occurred in only 11 patients. The highest incidence of complete heart block occurred in right bundle-branch block and left axis deviation when associated with heart disease, but the annual rate was only 4%/yr. Mortality was highest in those with left bundle-branch block, first-degree atrioventricular block, and left axis deviation (43%/yr). A one-year mortality of 65% (11/17) was noted for patients who had bifascicular block prior to the time of acute myocardial infarction.


The electrocardiographic response to maximal treadmill exercise of asymptomatic men with right bundle branch block. This study presents the results of maximal treadmill testing and cardiac catheterization in 40 asymptomatic and apparently healthy men with acquired right bundle-branch block. Eight of the men had significant angiographic coronary artery disease, and six of the eight only had single-vessel disease. The 40 men had normal maximal oxygen consumptions, normal maximal heart rates, and normal maximal blood pressure responses; none of the men had abnormal ST-segment changes in response to maximal treadmill testing. Thus, the sensitivity of exercise testing for coronary artery disease in men with right bundle branch block is uncertain. However, the apparently high specificity of exercise testing demonstrated by this study necessitates further evaluation for coronary artery disease in men with right bundle branch block who develop abnormal ST-segment depression in response to exercise testing.


Bronchial brushing in bronchogenic carcinoma. Factors influencing cellular yield and diagnostic accuracy. In a prospective study, varying the bronchial brushing technique through the flexible fiberoptic bronchoscope was examined for the effects of cellular yield and diagnostic accuracy. The yield of cells obtained from the 1.7-mm brush was increased by more than twofold when the brush and bronchoscope were withdrawn as a unit through the pharynx and nose, (nonwithdrawn brushing), rather than withdrawing the brush alone through the aspiration channel of the bronchoscope (withdrawn brushing). The greater number of total cells in the nonwithdrawn brushing specimen was largely due to squamous cells, and the yield of tumor cells by the two methods was similar. The yield of cells from the same brush withdrawn through a new suction adapter available on the bronchoscope (Olympus BF-B2) was significantly decreased, as compared with the withdrawn brushing. There was a further decrease using a shielded 1-mm brush. In 23 of 30 cases of proven carcinoma, the diagnosis was made by the single withdrawn brushing, and in 26 of the 30 by the single nonwithdrawn brushing, a difference which was not statistically significant. We conclude that diagnostic accuracy is not significantly enhanced by withdrawing the brush and bronchoscope as a unit through the pharynx and nose; use of a small shielded brush offers no advantage over a larger unshielded brush; modifications of flexible bronchoscopes, such as the adapter to improve efficacy of suction, should be evaluated for effects on harvests of cells from bronchial brushes before being put into general use.


Regression of pulmonary hypertension after mitral valve surgery in children. Operative management of rheumatic mitral valve disease. Forty-one children with advanced chronic rheumatic disease of the mitral valve had preoperative and postoperative hemodynamic studies. Twenty-three cases had open mitral commissurotomy, and 20 had mitral valvular replacement. After surgery the average pulmonary arterial systolic pressure in the group with valve replacement decreased from 78 to 42 mm Hg, the pulmonary vascular resistance decreased from 974 to 313 dynes sec cm 5, and the cardiac index rose from 2.29 to 4.15 L/min sq m. In the group with mitral commissurotomy, the average pulmonary arterial systolic pressure decreased from 90 to 63 mm Hg, the pulmonary vascular resistance decreased from 1,201 to 616 dynes sec cm-5, and the cardiac index rose from 2.5 to 3.5 L/min sq m. While all patients with mitral valve replacement showed a drop in pulmonary arterial pressure, the postoperative pressures were higher after commissurotomy in four patients, two of whom required a second operation of valve replacement. The study shows that in children, even severe degrees of pulmonary hypertension secondary to mitral valve abnormality is corrected.


Occult pulmonary abnormalities in asymptomatic asthmatic children. The pulmonary status of 178 asymptomatic asthmatic children with normal time-volume spirograms was further evaluated using flow-volume loops, body plethysmographic studies, and blood gas tensions in arterialized capillary blood. Residual volume (RV) was abnormal in 26%, total lung capacity (TLC) in 33%, RV/TLC% in 41%, and arterial oxygen pressure in 23% of them. All values for expiratory flow measured relative to observed vital capacity (VC), (ie, the forced expiratory volume in one second [FEV1], the mean forced expiratory flow during the middle half of the forced vital capacity [FEF25-75%; FVC], FEV1/VC, and the instantaneous forced expiratory flow after 75% and after 50% of the FVC has been exhaled) were normal, and VC was subnormal in only five instances, but flow rates measured relative to TLC were abnormal in 26% of the patients. Some abnormality of pulmonary function was present in all but 13% of these asymptomatic children. Reliance upon conventional evaluation of pulmonary function by forced expiratory spirograms and freedom from wheezing may frequently give the clinician a false impression of the true conditon of the lungs of the asthmatic child.


Bronchial adenoma. A clinicopathologic study. Among 28 patients with bronchial adenomas, 24 adenomas (86%) were of the carcinoid type. The 28 bronchial adenomas provided an incidence of 0.6% of all primary lung tumors seen in our institutions. There was a slightly greater preponderance of female patients and a greater incidence of the lision occurring in the right bronchopulmonary tree than the left. Symptoms of bronchial adenoma may exist for many years before the condition is diagnosed, and prolonged survival is recorded, even in the absence of surgical treatment. Although pneumonectomy was performed in several patients, lobectomy, bronchoplastic procedures, or sleeve resection of the affected area are generally recommended.


Experimental leukocyte-induced pulmonary vasculitis with inquiry into mechanism. Intravenous transfusions of washed allogeneic or autologous leukocytes in rabbits resulted in lesions of pulmonary periarteritis 48 hours later. Intact leukocytes were required. Systemic anaphylaxis, generalized Shwartzman reaction, alternate pathway complement activation and inert particle microembolism failed to produce identical lesions. Leukocytes tagged with radioactive chromium were found within arterial thromboses with proximal vasculitis. Generation or release of inflammatory factors plus thromboembolism would explain the pathogenesis of the lesions described. Specific mechanisms may be quite complex. Similar lesions have not been described in studies of pulmonary leukocyte entrapment or experimental microembolism of the lung. This model may be useful for studying pathogenetic mechanisms in pulmonary vasculitis and may have clinical implications.


The volume of isoflow and increase in maximal flow at 50 percent of forced vital capacity during helium-oxygen breathing as tests of small airway dysfunction. The purpose of this report is to review the role of helium in the early detection of obstructive pulmonary disease. The underlying physiologic mechanisms of the volume of isoflow (the volume at which flow was the same with the subject breathing air and breathing a mixture of 80 percent helium and 20 percent oxygen) and increases in maximal flow at 50 percent of vital capacity (Vmax50) after breathing helium are reviewed. These tests are able to detect physiologic abnormalities in asymptomatic subjects when the results of other tests are normal; and following cessation of smoking, abnormal results may be reversible. The volume of isoflow is increased when maximal flow is reduced because of loss of elastic recoil or increase in upstream resistance. The increase in Vmax50 after breathing helium appears to be relatively specific for the caliber of the small airways, being uninfluenced by loss of elastic recoil; it can further help to localize the major site of obstruction to either small or large airways. At present, random screening for early unsuspected disease is not warranted, and these tests remain an investigative tool.


Low-dose amphotericin B therapy for acute pulmonary histoplasmosis. A patient wtih acute epidemic pulmonary histoplasmosis was treated with 500 mg of amphotericin B. Traditionally, such patients have not been treated, since the illness is usually self-limited; however, fatalities have been reported, and some authorities have recommended therapy with small doses of amphotericin B. Patients with acute pulmonary histoplasmosis who are acutely ill should be considered for low-dose treatment with amphotericin B, inasmuch as they are likely candidates for early dissemination. Cures have been reported with as little as 105 mg of amphotericin B administered intravenously.


Isolated massive chylopericardium. Complication of open heart surgery for aortic valve replacement. Chylopericardium following open-heart surgery for aortic valve replacement in a 53-year-old woman is described. Five weeks after surgery, the chylous pericardial effusion was detected when the patient developed recurrent chest pain and cardiomegaly. Treatment included drainage of the fluid and partial pericardiectomy. No recurrence of the chylopericardium was observed in this patient up to 14 months after surgery.


Myocardial dysfunction and hemolytic anemia in a patient with Mycoplasma pneumoniae infection. A patient with evidence of myocardial abnormalities and hemolytic anemia is described, in whom the responsible pathogen appeared to be Mycoplasma pneumoniae (as indicated by a 64-fold rise in complement-fixation titers, and by a change in cold-agglutinin titers from 1:8 to 1:4,096). Both cardiac and hematologic problems occurred during the recovery phase from pneumonia and were associated with marked deterioration in the patient's clinical status. Electrocardiographic and serum enzymatic changes mimicked the patterns seen in acute myocardial infarction.


Echocardiographic diagnosis of intraventricular clot. The literature contains many reports of the echocardiographic findings in left atrial myxoma and clot; however, descriptions of left ventricular thrombus or tumor are rare. We discuss here the echocardiographic findings in a patient with a large apical left ventricular thrombus which was confirmed both angiographically and pathologically. The importance of echocardiographically examining the area below the mitral valve near the apex of the left ventricle, where most of the thrombi are located, is stressed.


Idiopathic spontaneous pneumothorax. Electron microscopic study. A lung biopsy obtained from a patient following a second occurrence of idiopathic spontaneous pneumothorax was studied by electron microscopy. A remarkable increase in septal mass was a notable finding. Proliferation of the interstitium was due to an abundance of collagen and elastic fibers. In additon, a proliferation of type 1 and type 2 epithelial cells was seen.


Silicosis in slate pencil workers. A clinicoradiologic study. We present a study of 151 persons working in slate-pencil manufacturing industries located in the Mandsaur district of Madhya Pradesh, India. Cough, dyspnea, and pain in the chest were the important symptoms. Cyanosis, rhonchi, and crepitations were found in varying numbers of cases. The chest x-ray films were abnormal in 85 cases.


Resistant ventricular tachycardias and recurrent cardiac arrests. 96 episodes. A 66-year-old man suffered an acute myocardial infarction complicated by multiple episodes of ventricular tachycardia and 96 episodes of ventricular fibrillation requiring cardioversion over a period of 55 days. Following ventricular aneurysmectomy, the ventricular tachycardia persisted. This converted to regular sinus rhythm with a regimen of disopyramide phosphate, quinidine, and propranolol.


Pulmonary mycetoma due to Coccidioides immitis. Pulmonary mycetoma due to Coccidioides immitis has been reported on three occasions. The present case is the fourth such report occurring in a patient with widely disseminated disease. Spherules and hyphae were found in the specimen. While the active pulmonary and extra-pulmonary lesions responded well to therapy with amphotericin B, resection was required to eliminate the residual mycetoma and its attendant hemoptysis.


Pharmacokinetics of ampicillin, cephalothin and doxycycline in various tissues of the rat. To study the behavior of antibiotics in the tissues, rats were sacrificed repeatedly in groups of six, after the injection of 25 mg/kg ampicillin, 100 mg/kg cephalothin or 10 mg/kg doxycycline. These antibiotics were bioassayed in ten different organs. Standards were established for each organ by using identical organs, thus avoiding errors caused by tissue binding or inhibition. Penetration into the tissue is very fast. Compared to serum levels, lung, muscle, heart, testicle and spleen, levels are higher for doycycline, lower for ampicillin and variable for cephalothin: for example, lung/serum ratio at 1 h is 2.2, 0.5 and 1.1, respectively; muscle/serum is 2.3, 0.2 and 0.18. The decrease in tissue levels parrallels that in the serum for doxycycline, but is slower for ampicillin. The hepatic penetration of cephalothin is less than that of doxycycline or ampicillin. Levels are higher in the renal cortex than in the medulla for doxycycline, lower for cephalothin, and similar for ampicillin. The data enabled calculation of tissular pharmacokinetics. They have practical implications in the selection of antibiotics.


Association of halogenated isoxazolylpenicillins with penicillinase-sensitive beta-lactam antibiotics. Microbiological evaluation on beta-lactamase-producing Enterobacteriaceae. The validity of nonsimultaneous association of penicillinase-sensitive beta-lactam antibiotics with halogenated isoxazolylpenicillins was tested in various Enterobacteriaceae strains. With several bacterial strains, expecially if producers of beta-lactamase type IV, exposure of either the bacterial suspensions of the brothsupernatant to the isoxazolylpenicillins appears both in vivo and in vitro to reduce the extent of subsequent hydrolysis of penicillinase-sensitive beta-lactam antibiotics.


[Intraoperative instrumental autotransfusion. 1st experiences in vascular surgery and traumatology]. Intraoperative autotransfusion with the Bentley-ATS system was performed in 22 patients, saving a total of 98 000 ml of their own blood. In addition 77 000 ml of homologous blood were given, intraoperatively. Eleven patients underwent major vascular surgery and 11 were operated for major traumatic injuries. There was a total of 11 deaths overall but none related to the autotransfusion. It is concluded that intraoperative autotransfusion is a safe and simple method of rapid transfusion which can save significant volumes of precious homologous blood.


[New technic of the transjugular cava blocking in the removal of acute pelvic vein and inferior vena cava thrombosis]. Thrombosis of the inferior vena cava rarely occurs. However, it mostly develops by continous growth from thrombosis of the deep leg and pelvic veins. Thrombus formation in the inferior vena cava carries a potentially lethal risk because of possible involvement of the renal veins with consecutive renal failure or development of fulminant pulmonary embolism. Therapy of choice consists in early diagnosis and immediate thrombectomy. Choice of the operative procedure is of the utmost importance for immediate and late results. Our technique consists of inserting a balloon catheter via a side vessel of the internal jugular vein and placing it into an infrarenal position, where it is blocked, thereby preventing blood flow from the area to be cleared. Three cases in which this technique was employed are presented.


[Hemothorax after abdominal vagotomy. Diagnostic problem]. Selective or selective-proximal vagotomy has increased in preference as surgical treatment for uncomplicated duodenal ulcer disease. An unusual immediate complication of transabdominal vagotomy is the hemothorax. Few cases of this complication have been reported in literature. Our case represents a variation with simultaneous presence of a both-sided hemothorax. Although the exact etiology of this complication remains obscure, we try to explain this spontaneous hemothorax by operative injuries of subpleural vessels.


[Bronchobiliary fistula. Pathogenesis, diagnosis, therapy]. The case demonstrated shows the pathomechanism of bronchobiliary fistula. In most cases, bronchobiliary fistulae are caused by stenosing lesions of the common bile duct. For diagnosis the combined cholangio-bronchography is the preferred method. Removal of the obstructing lesion is the aim of operative treatment. Usually spontaneous healing of the bronchobiliary fistula results.


[Clinical importance of passage time and reflux after small intestine bypass surgery]. 1. After jejunoileostomy patients rapidly loose body weight. This loss of weight may turn out to be too small in cases where there is a reflux. 2. There is a direct relationship between the rapidity of the loss of body weight and the duration of gastro-intestinal passage. The shorter the duration of passage, the quicker the patient's loss of body weight. 3. Duration of passage remains approximately constant during the first 9 months after jejunoileostomy as shown by the evaluation of 52 patients. From the 15th month onward the duration of passage rises significantly and reaches 2-3 times its initial value from the 18th month onward. Simultaneously, a cessation of the loss of body weight is to be observed owing to an adaptation to the malabsorption.


[The Rapeutic principles in malignant rectal polyps based on late results]. The late results of various treatment of 114 patients with malignant rectal polyps were found to be similar over a 5-25-year follow-up. On this basis, the following principles of therapy were established: 1. All rectal polyps should be removed completely. 2. Local removal of a malignant polyp, looking macroscopically benign and of favorable size and location, is justified, even though a cancer - not infiltrating the stalk - is situated in the head of the polyp. In any other case a radical operation is indicated. 3. Patients should be held under a life-long supervision. 4. The control should be performed as an organized care.


[Recording of the surgical procedures and postoperative complications in general surgery]. With selected examples from general surgery, a better statistical elaboration of patient's data by means of operation and complication classification is demonstrated. The use of an operation and a complication key is presented. The advantage of such a classification key in documentation is the possibility of maintaining an accurate yearly review of all therapeutical methods in surgery.


[Experimental splenic artery ligation. Changes in hemodynamics and immunoreaction]. In 27 male rabbits the splenic artery was ligated. During the procedure and 10-14 days postoperatively, orthostatic regulation using a tilting table, the hemogram (RBC + WBC), and concentration of immunoglobulins (IgG and IgM) were measured. The arterial and venous blood pressure (CVP and portal vein) were only slightly increased whereas there was a marked (up to 40%) increase in the area of the mesenteric veins compared with the preoperative values. The orthostatic tolerance by 90degrees was uniformly diminished. No changes were seen in the hemogram nor in the immunoglobulins. Macroscopically and microscopically a fibrotic transformation of the spleen was seen.


[Reconstruction of intraoperative ureteral injury]. Intraoperative injuries of the upper urinary tract are seldom and mostly found in the prevesical segment of the ureter. The immediate plastic reconstruction by reanastomosis or regeneration shows positive results. Depending on the localization of the ureter trauma, ureterocystoneostomy, end to end anastomosis, or pyeloureteroneostomy are the most successful reconstruction methods.


[Sacrococcygeal chordoma. Radical operation, a problem]. A sacrococcygeal chordoma was observed over a 7-year follow-up period. Primarily there were only local recurrences. The long-term results of the treatment of sacrococcygeal chordoma are bad. The indication of hemipelvectomy or hemicorporectomy as surgical treatment is therefore discussed.


[Congenital aplasia of the diaphragm].

[Congenital aplasia of the diaphragm]. The present paper reports on a complete left-sided aplasia of the diaphragm. In this especially risky case (birth weight 2000g) the left hepatic lobe was used for separation of the abdominal from the thoracical space in order to quickly terminate the surgical operation. Very probably the child would not have survived a major plastic operation. As the control examination (annual control) showed, the child is developing quite normally. Until now tests of the hepatic function did not render any pathologic findings either.


[Rare abnormality of the extrahepatic bile duct and the V. coronaria ventriculi]. An accessory bile duct was observed during anatomical dissection of the body of an 84-year-old man. The duct originated in the superior area of the lateral segment of the liver and penetrated the stomach wall in the region of the pylorus. Histologic examination revealed that the duct passed through the pyloric sphincter and could be traced to the submucosa of the pars superior of the duodenum. In addition the left gastric vein was enlarged and instead of opening into the portal vein, passed directly to the superior area of the lateral segment of the liver.


[Stomach duplication].

[Stomach duplication]. The eighty-four cases of stomach duplication known to date from world literature are presented including one case of the authors' own experience. The most varied theories of pathogenesis are discussed, as well as the very different clinical course the disease may take, and the diagnostic difficulties presented by X-ray examination. Finally, attention is drawn to the current use of the scintigraphy, which has broadened the diagnostic possibilities.


[Persistent duodenal septum in an adult]. A case of duodenal obstruction by a congenital duodenal web in a 34-year-old woman is presented. A mucosal diaphragm obstructed the duodenum. It showed an excentric opening of 0.8 cm diameter, but the dilated diaphragm caused a total stop during the last months. Despite a typical history, exact X-ray, and endoscopic examination, the correct preoperative diagnosis was not found, because nobody thought it possible, that a mucosal diapharm of the duodenum could persist for 34 years.


[Recidivism of Crohn's diseases. Indication and therapeutic problems of reintervention]. The recurrence of Crohn's disease often presents problems in the indication for surgery. Reoperation is indicated in all recurrent complicated cases and in postoperative complication not specific for Crohn's disease. However relaparotomy should be performed only after conservative measures have proved unavoiding. In the Department of Surgery at the University Hospital in Mainz 153 patients with Crohn's diseases were treated over an 11-year-period. Of 310 patients operated for Crohn's disease 153 reoperations were performed in 73 patients. The aim of reoperation should be the prevention of  further complications. In view of the individually differing courses of the disease no general guidelines can be laid down for the indications for laparotomy.


[Localization, prophylaxis and therapy of subphrenic abscess]. Main symptoms and causes of subphrenic abscess are described. Localization is possible using Gallium 67 scanning. Prophylaxis and surgical approach are illustrated. In 75 patients of the surgical clinic of the University of Hamburg, the subphrenic abscess was drained by an anterolateral extrapleural incision through the diaphragm. Positive identification and localization are necessary to prevent contamination of the peritoneal cavity. Scintigraphic Gallium 67 scanning is also useful to identify synchronous subphrenic (bilateral) abscesses.


[Technique, difficulties and results of endoscopic retrograde cholangio-pancreatography (ERCP)]. Endoscopic retrograde cholangio-pancreatography belongs to the diagnostical equipment of gallduct obstruction and obturation. ERCP is indicated if any doubts arise with the usual clinical diagnostic methods, laboratory, or x-ray studies. This paper presents the technique of ERCP and the several steps in its operation: pylorus passage, description and evaluation of the papilla of Vater and insertion of the papilla. Daily practice and patience produce successful work without complications. Rate of complication in 604 ERCP procedures = 2%. No lethal outcome was observed.


Mechanisms for sister chromatid exchanges and their relation to the production of chromosomal aberrations. By taking advantage of the fact that fluorescent light (FL) induces strand breaks only in bromodeoxyuridine(BrdUy-substituted DNA, and that those breaks eventually lead to the formation of sister chromatid exchanges (SCEs), the response of SCEs to FL was studied carefully in Chinese hamster chromosomes in which, out of four DNA strands, BrdU-substitution had occurred either in one or three strands. The FL-induced SCE frequency did not differ greatly between these two types of chromosomes. However, when they were submitted to caffeine treatment, a drastic increase in the frequency was detected in the trifilarly-substituted chromosomes while a significant decrease occurred in the unifilarly-substituted chromosomes. Based on these results, a working hypothesis was developed that the SCE can arise by at least two different mechanisms, one operating at replicating points probably utilizing the machinery of DNA replication, and the other acting only in the post-replicational DNA portion, probably in a similar fashion as assumed in a general model of crossing over in the eukaryote. These dual mechansims may account for the discrepancy encountered in the explanations of the induction of SCEs by various exogenous agents as well as spontaneous SCEs. The present study also showed that some, but clearly not all, of chromatid deletions are the outcome of the failure to complete SCEs arising through these mechanisms.


Somatic pairing and meiotic nonrandom disjunction in a pericentric inversion of Hylemya antiqua (Meigen). An asymmetrical pericentric inversion in the onion fly, Hylemya antiqua was studied. Somatic pairing was studied in young eggs from test-and sibcrossed inversion heterozygous females which gave four and seven distinguishable karyotypes respectively. From these seven, three are balanced: the normal type, the inversion heterozygote and homozygote, and four are unbalanced recombinant karyotypes descending from crossovers in the loop. In all types at all mitotic stages the centromeres are paired. The telomeres only show association during prophase but this decreases from mid to late prophase. Quantitative analysis of the four different crossover products as produced by inversion heterozygous females showed the presence of nonrandom disjunction. A significant disparity was observed, viz. the normal chromosome was taken up preferentially into the functional gamete compared to the inverted chromosome. Dragging of long chromatids in the asymmetric dyad during M I-A I is a possible explanation of this feature.


Differential staining of polytene chromosome bands in Chironomus by Giemsa banding methods. Two Giemsa banding methods (C banding and RB banding) are described which selectively stain the centromere bands of polytene salivary gland chromosomes in a number of Chironomus species. - By the C banding method the polytene chromosome appearance is changed grossly. Chromosome bands, as far as they are identifiable, are stained pale with the exception of the centromere bands and in some cases telomeres, which then are intensely stained reddish blue. - By the RB method the centromere bands are stained bright blue, whereas the remainder of the polytene bands stain red to red-violet. - Contrary to all other species examined, in Chironomus th. thummi numerous interstitial polytene chromosome bands, in addition to the centromere regions, are positively C banded and blue stained by RB banding. In the hybrid of Ch. th. thummi X Ch. th. piger only those interstitial thummi bands which are known to have a greater DNA content than their homologous piger bands are C banding positive and blue stained by the RB method whereas the homologous piger bands are C banding negative and red stained by RB banding. Ch. thummi and piger bands with an equal amount of DNA both show no C banding and stain red by RB banding. - It seems that the Giemsa banding methods used are capable of demonstrating, in addition to centromeric heterochromatin, heterochromatin in those interstitial polytene chromosome bands whose DNA content has been increased during chromosome evolution.


DNA content in the genus Xenopus.

DNA content in the genus Xenopus. Nuclear DNA amounts were determined by cytofluorometry for twelve species and subspecies of the genus Xenopus. Absolute values, in pg per nucleus, were obtained by direct comparison with human lymphocyte nuclei. The lowest DNA amount (3.55 pg) was found in X. tropicalis, which possess only 20 chromosomes, and the highest (16.25 pg), in the hexaploid X. ruwenzoriensis, with 108 chromosomes. The two recently discovered tetraploid species, X. sp.n. and X. vestitus have, respectively 12,57 and 12.83 pg of DNA. Among the species and subspecies with 36 chromosomes, the DNA content ranges from 6.35 to 8.45 pg.


Diplotene chromosomes of Xenopus hybrid oocytes. Observation on meiotic diplotene chromosomes from oocytes of Xenopus species and subspecies hybrids are reported. Species interrelationships are established on the basis of the number of bivalent in the respective hybrids. Polyploid oocytes were found and their origin by supplementary endoreduplication placed at the differentiation stage of gametogenesis when oogonia become oocytes. The significance of polyploid oocytes for speciation is discussed.


An investigation of some problems concerning nucleolus organizers in salamanders. Observed differences in the sizes of lampbrush nucleolus organizers in Plethodon cinereus have been shown by in situ hybridization to reflect true molecular differences in the numbers of ribosomal cistrons located at these organizers. Likewise, from in situ hybridization experiments on lampbrush and spermatocyte chromosomes it has been shown that animals may be, and indeed usually are, heterozygous with respect to the numbers of ribosomal cistrons on each half of the nucleolus bivalent. Filter hybridizations carried out on 33 males from a New Jersey population and 20 males from a Connecticut population have shown a 7.5-fold range in the numbers of ribosomal cistrons per diploid cell in the New Jersey population, and a 2.5-fold range in the Connecticut population. In view of the general heterozygosity of nucleolus organizers in these animals, the actual range in nucleolus organizer sizes in the New Jersey population is estimated to be at least 15-fold.


[Transmission analysis of the B chromosomes in Locusta migratoria migratorioides R. et F. (Orthoptera, Acrididae) (author's transl)]. In a African grasshopper population of Locusta migratoria migratorioides reared in the laboratory, B chromosome transmission is analysed in progeny of pairs taken at radom from the population. An accumulation mechanism of Bs exists in the females which presumably results from preferential egregation of the Bs in the female pronucleus. The analysis also shows B chromosome elimination during embryonic and larval development by means of mitotic non-kisjunction: these non-disjunctions induce interfollicular variations in the number of Bs but all the cells of a follicle have the same number of Bs. The frequency of animals with B chromosome rises from 34% to 75% as the diurnal temperature rises from 27 degrees C to 35 degrees C. Thus frequency is controlled by genetic and environmental factors.