Molecular size of IgG in patients with focal glomerulosclerosis.

Nineteen patients with focal glomerulosclerosis and with anomalously high clearance of IgG into the urine have been investigated by G.200 column chromatography. The findings are compared with normal sera, with 14 patients with minimal change disease and with 12 patients with proliferative glomerulonephritis. No significant reduction in the molecular size of IgG was found as compared with normal sera and the other diseases in 18 of the patients. In patients with minimal change disease and focal glomerulosclerosis an increased proportion of the IgG eluted in the void volume


Uremic pericarditis: a prospective echocardiographic and clinical study.

During a 14 month period 59 male patients with chronic renal failure who were candidates for chronic hemodialysis (HD) were evaluated clinically and echocardiographically for pericarditis. All were evaluated prospectively prior to or at the initiation of HD. Definite pericarditis was present in 8, all of whom were severely uremic and required initiation of HD on a semiemergent basis rather than electively (i.e., preselected level of renal function). In 6 of these 8, pericardial effusion responded to dialysis alone, one required pericardiectomy because of hypotension complicating dialysis, and one expired during a right atriogram. Patients dialyzed on an elective basis were all free of pericarditis at the initiation of HD. Pericarditis arising some months after the initiation of HD was a less frequent problem. It is concluded that (a) the incidence of pericarditis in the uremic state is decreased by early initiation of HD before advanced uremic symptoms have developed; (b) pericarditis present at the initiation of HD usually but not always is resolved with the initiation of HD; (c) echocardiography is an important clinical and epidemiological toole to investigate pericarditis in uremic patient populations.


Unusual aspects of the dialysis disequilibrium syndrome.

In five patients with chronic renal failure, rapid correction by dialysis of hypertension and/or high blood urea levels provoked acute neurological disorders, followed by slowly reversible neuropsychiatric disturbances. Focal EEG alterations were noted in three patients with normal carotid angiograms. Our cases differed from those usually described as suffering from the dialysis disequilibrium syndrome because of their duration, the severity of mental disturbances, and the asymmetrical pattern of EEG abnormalities. We propose that the symptoms observed could be due to cerebral ischemia. This possibility emphasizes the importance of limiting the duration and efficiency of the first dialyses in patients with severe hypertension and high nitrogen retention, especially if high performance dialyzers are used.


Sexual behaviour of hemodialyzed patients.

18 married men on home dialysis and 10 of their wives were interviewed (structured interview) to evaluate sexual adjustment. The frequency of intercourse prior to the onset of their disease was reported to be 3.4/week by the patients and 2.4/week by their wives. During maintenance hemodialysis, frequency was reported to be 1.7/week by the patients and 1.0/week by their wives. If libido prior to the disease was rated 100%, the patients reported their libido at the time of the interview as 66+/-34%; only 5 rated their libido as less than 50% of their libido prior to the onset of their disease. After the start of dialysis, considerable time was required before a stable state of sexual activity was reached (13.9+/-7.4 months), presumably reflecting the time required for adaptation to the procedure, loss of anxiety and restoration of physical well-being. Except in older patients, there was good agreement between the feeling of physical fitness as reported by the patients and sexual performance as reported by both the patient and his spouse.


Hemosiderosis in a patient on regular hemodialysis: treatment by desferrioxamine.

Hemosiderosis following regular administration of parenteral iron was observed in a patient receiving maintenance hemodialysis. Infusions of desferrioxamine in doses of 2,3 and 4 g each resulted in the removal of approximately 45 mg of iron during dialysis. Desferrioxamine 2 g was infused thrice weekly during dialysis for twelve months. Body iron stores, as judged by liver iron and serum ferritin concentrations, fell by about half. This agrees well with the result calculated from the amount of iron administered and the amount removed during dialysis.


Scanning electron microscopy of the urinary tract. A scanning electron microscopic investigation of the luminal surface of the entire urinary tract of the Wistar rat was performed. This report defines criteria for identifying different segments of normal urinary tract on the basis of scanning electron microscopic observations of the epithelial surface. The study was undertaken to provide a reference for future studies of changes in urinary tract morphology resulting from injury or disease.


Platelet function in patients on long term peritoneal dialysis.

Platelet function studies were performed on 18 patients with end stage chronic renal failure receiving treatment by long-term peritoneal dialysis. The results of these studies were compared with previously reported data on healthy volunteers, non-dialyzed patients with chronic renal failure and patients treated by hemodialysis. Platelet adhesiveness was impaired and, unlike the other patient groups, there was no relationship between adhesiveness and serum creatinine. Platelet aggregation to both ADP and adrenaline chloride was normal, whereas marked impairment was seen in non-dialyzed patients with severe chronic renal failure and patients receiving hemodialysis. The results suggest that different uremic retention products affect these different phases in the platelet adhesion-aggregation reaction and that the peritoneal membrane is more permeable to that dialyzable factor which inhibits aggregation than conventional hemodialysis membranes. The studies are of interest both in consideration of adequacy of dialysis and in studies into the nature of the platelet defect in uremia.


Renal tubular defects in recurring bilateral nephrolithiasis.

A metabolic study was performed in 28 patients with bilateral recurrent calcium-containing renal staghorn calculi and chronic pyelonephritis ("obstructive nephropathy"). Fourteen had normal GFR and 14 mild renal insufficiency. Ten normal subjects were used as controls. Under basal conditions, polyuria and negative sodium balance were commonly observed in patients with obstructive nephropathy and normal renal function. After an acute acid load (NH4Cl) an acidifying defect, i.e. high values for urine pH and reduced excretion of titratable acid and ammonium, was observed in 64% of patients with normal GFR and in 71.4% of those with renal insufficiency. During intravenous infusion with neutral sodium phosphate, the urine pH changed little but the rate of excretion of titratable acid increased in direct proportion to that of urinary phosphate in both groups of patients. These results, associated with the finding of normal blood pH in almost all patients, lead to the conclusion that an incomplete Type 1 or "distal" renal tubular acidosis is a frequent complication of obstructive nephropathy secondary to bilateral nephrolithiasis. The anatomical abnormalities of renal tubules and collecting ducts and the superimposed interstitial nephritis might be the pathogenetic factors responsible for the acidifying defect and for the impairment in sodium and water conservation.


Free phenols in chronic renal failure.

Serum total free phenols are elevated in chronic renal failure, acute renal failure and hepatic coma. Being partly protein-bound, phenols behave during dialysis in a similar manner to considerably larger molecules which are not protein-bound. In view of their potential toxicity they should be considered as an alternative to 'middle molecules'. Patients on regular hemodialysis have retention of phenols if their post-dialysis serum creatinine is above 6-7 mg/dl. Patients on short time dialysis have high pre-dialysis neutral phenol levels. Such levels are sufficiently high to suggest a role in the genesis of neurological symptoms, anemia and bone disease. Certainly pre-dialysis free phenols reflect adequacy of dialysis.


Isoniazid pharmacokinetics in patients in chronic renal failure.

INH pharmcokinetics was studied in 2 groups of patients in chronic renal failure. In the group on conservative treatment, INH half life was prolonged, but was not related to the degree on renal impairement. In the hemodialysis group 73% of the INH given was removed by dialysis within 5 hours. If INH is to be used in the presence of renal failure, individual half life estimations should be performed in order to determine dosage frequency. In patients on hemodialysis, therapy should be given post dialysis. Alternatively, drugs not dependent on renal failure, e.g. rifampicin, may be preferable.


Pleural dialysis in acute renal failure.

An 80 day old infant developed acute renal failure postoperatively after nephrectomy for Wilm's tumor. Pleural dialysis was utilized to control electrolyte imbalance of acute renal failure. Function of pleura as a dialyzing membrane was evaluated for the clearance of urea and creatinine.


Life-threatening infections in pregnancy.

Infection remains a major cause of maternal morbidity and mortality. Those entities that are most likely to threaten the life of the pregnant woman have been reviewed. Although intrapartum and postpartum pelvic infections consitute the majority such serious infections in pregnancy, attention has also been called to several less frequent but potentially lethal nonpelvic infections.


Difficulties in delivery, including shoulder dystocia and malpresentations of the fetus.

Shoulder dystocia is a true obsteric emergency. It may be suspected in large multiparous women, women who have previously delivered large babies, prolonged pregnancy, women who make poor progress in labor, and when the fetus seems very large to palpation. Women with abnormal pelves should be suspect. More liberal use of cesarean section in these situations will reduce the incidence of shoulder dystocia. It is important to have a carefully considered plan of action if shoulder dystocia does occur. The most helpful and definitive maneuver is extration of the posterior arm. Malpresentations cause acute emergencies mainly because of the associated increased incidence of prolapse of the cord. This possibility should be evaluated immediately when rupture of the membranes occurs. Prompt delivery by cesarean section is the treatment of choice with this complications.


Ureteral injuries associated with gynecologic surgery: prevention and management.

Gynecologic surgery is responsible for most of the ureteral injuries that occur. The "easy" operation--the "simple" abdominal hysterectomy--and not the technically difficult pelvic one, is responsible for most ureteral injuries. Total abdominal hysterectomy accounts for almost 50% of the genitourinary fistulas and perhaps 80-99% of all surgical ureteral injuries. This problem will persist until a most important surgical axiom is applied routinely during the accomplishment of all pelvic operations: With all dissections, the contiguous structures subject to injury must be exposed. This step not only will avoid injuries to the ureter but also will facilitate an equally important aspect, that is, urinary tract injuries must be recognized at the time of operation. With recognition and adequate repair, problems such as fistula formation and serious morbidity (and litigation) can be avoided almost entirely. Because the gnecologic surgeon frequently will find that urologic consultation is not available at the time of urinary tract injury, he or she must be aware of and familiar with the various ureteral reconstructive procedures that may be required. The gynecologic surgeon must devote time and study to the management of urinary tract injuries before their occurrence. All pelvic surgeons eventually will encounter ureteral problems. The methods of bladder mobilization and ureteroneocystostomy should be within the ability of all who operate within the pelvis. When extensive damage has occurred and a urologist is not available, the gynecologist who is unfamiliar with the more demanding techniques (that is, ureteroureterostomy, bladder flaps, ileal conduits) should avoid additonal damage to the urinary tract and accomplish a simple catheter ureterostomy, deffering the definitive repair for a urologist.


Management of ovarian carcinoma in young women.

On the basis of available information, the following criteria regarding ovarian carcinoma may be considered for the young patient who has not completed her family and is desirous of further childbearing. Any ovarian enlargements must be promptly and adequately evaluated. A lesion of high grade or high stage is not amenable to conservative surgery, and definitive total abdominal hysterectomy, bilateral salpinog-oophorectomy with or without partial omentectomy, and subsequent chemotherapy or radiotherapy are indicated. In the individual who has a low-grade and intracystic or encapsulated ovarian neoplasm, conservative surgery may be considered, provided there is no evidence otherwise of any periotneal or other spread and particularly if the opposite ovary is histologically evaluated, preferably by wedge resection. Data have indicated that this is a reasonable process to consider, and if followed carefully this should allow these individuals to accomplish their childbearing function with minimal risk. In general, because of the bilaterality of ovarian tumors, such conservative surgery probably is indefensible unless these riged criteria are met. It would also seem preferable to complete the surgical procedure with hysterectomy and salpingo-oophorectomy once the patient's family is complete, thus obviating any possible appearance of a malignant tumor in the remaining ovary. The use of exogenous estrogesn would also seem far preferable to the risk of an insidious low-grade tumor that could not be adequately followed.


Scheuermann's kyphosis: a form of osteoporosis?

A high frequency of abnormalities were noted in radiographic measurements of bone density, microradiography of the iliac crest, serum alkaline phosphatase, urinary hydroxyproline and dietary calcium intake in 12 patients with Scheuermann's juvenile kyphosis. Scheuermann's kyphosis may be a manifestation of generalized skeletal disease which becomes symptomatic during the growth spurt of puberty.


The clinical biomechanics of scoliosis.

Removal of the posterior elements will allow increased correction of axial deformity, in scoliosis. The clinician may take advantage of the creep and relaxation characteristic of the tissues to improve efficiency of correction. Axial loading has been shown theoretically to be more efficient for the more severe curves, (greater than 53 degrees) and transverse loading more efficient for the less severe curves (less than 53 degrees). Combined loading is always more efficient than either type alone. The Milwaukee brace can be just as effective as a cast in resisting deforming forces in scoliosis. Removal of axillary supports or thoracic pads or not wearing the brace when recumbent reduces the effectiveness of the Milwaukee brace. The strength of the thoracid lamina is a limiting factor in the amount of forces that may be applied to correct the deformity; 30 kilopond (65.8 lb) is the upper limit of this force. Coughing or buckling can apply dangerously high forces with the Harrington rod. Greater surgace contact of the hook to the lamina and small increments between notches on the rod may increase the tolerance limits of the system. Compression rods on the convex side probably add little or no correctional value. The Dwyer technique is biomechanically sound and effective and has the additional advantage of applying asymmetrical loads to the epiphyseal plates.


Pyogenic infections of the sacro-iliac joint.

In 3 cases of pyogenic infection of the sacro-iliac joint, the diagnosis was difficult. Limp, buttock pain and upper sciatica were the most common presenting symptoms. Differential limitation of hip motion, positive straight leg raising, a positive Gaenslen test and pain on pelvic compression were frequent fingings. Increased E.S.R., W.B.C. count and fever were seen in 2/3 cases. Plain and tomographic X-rays are often helpful but bone scan has been helpful in localizing early lesions. Treatment after early diagnosis may consist of antibiotics and immobilization alone while in the more chronic cases surgical drainage and debridement may be necessary.


Bone injuries due to tetany or convulsions during hemodialysis.

Two patients with long standing uremia sustained bone injuries due to tetany in one, and convulsions secondary to hemodialysis-induced alkalosis and hypomagnesemia in the other. In the former, there were multiple fractures involving the scapula, clavicles and femoral necks. In the latter, there was a slipped capital femoral epiphysis. Caution should be exercised against tetany or convulsive episodes which may cause bone injuries during hemodiaylsis in severely osteoporotic patients. In patients with progressive renal osteodystrophy, prevention of severe osteopenia by timely kidney transplant or subtotal parathyroidectomy is an important preventative measure.


Candida arthritis of the knee joint.

Candida albicans arthritis is unusual but does occur perhaps more often than recognized. The most common site of infection is the knee joint in the adult and can be related to contamination of the joint at the time of intraarticular injection of corticosteroids.


Aneurysmal bone cyst: evaluation of resection and of curettage in 20 cases.

The clinical, angiographic and histological aspects of 20 cases of aneurysmal bone cyst suggest that angiography is a valuable aid in the diagnosis of a cyst, differentiating it from other cystic bone lesions. Angiographic information also has a certain bearing on the origin of the lesion. It was demonstrated that other, benign, lesions may exist adjacent to the cyst or prior to it; in most cases, however, the cyst appears in a bone which is otherwise normal. The failure to differentiate between aneurysmal bone cyst and giant cell tumor in relation to sex, age, localizaiton, morphology, and clinical course (e.g. tendency of recurrence and malignant transformation) may be responsible for confusion in the literature on these lesions. Good results of treatment are achievable by resection en bloc and by resection, or curettage with bone grafting. Curettage alone is inadequate. Only two recurrences (10%) were recorded in the present series during the average follow-up period of 4.5 years.


Solitary bone cyst with epiphyseal involvement: a case report.

A large solitary bone cyst involving the epiphysis produced 5.0 cm shortening of the proximal humerus in a 15-year-old girl. Biopsy revealed the cyst was filled with thin yellow fluid under pressure and lined by a fibrous membrane. X-rays 9 months after biopsy demonstrated progressive cyst obliteration. A review of literature revealed no similar case. It is postulated that solitary cysts rarely may involve the physeal and epiphyseal structures and thereby retard longitudinal bone growth.


Myositis ossificans traumatica in a young child: a case report.

This is a case report of a 2-year, 11-month-old boy with traumatic myositis ossificans of the deltoid muscle, possibly the youngest child with this condition reported in the literature. The lesion, removed 7 months after injury because of pain, showed no evidence of spontaneous regression.


Eosinophilic granuloma of the proximal tibial epiphysis.

This is a 3-year follow-up report of an eosinophilic granuloma of bone occurring in a growing epiphysis. The lesion occurred in a 6-year-old boy and is only the third such case reported in the literature. Eosinophilic granuloma should be considered in the differential diagnosis of lytic lesions of the epiphysis in childhood.


Osteoid osteoma of the ulna in a Negro child: a case report.

Osteoid osteoma seems to have been reported only twice before in a Negro child. The lesion is also unusual in the ulna. Treatment by en bloc resection bone graft of a large surgical defect was successful.


Osteoid osteoma of a vertebral body: report of a case with extension across the intervertebral disk.

An 18-year-old woman was evaluated for aching mid thoracid back pain of 4 years' duration. At 13 degrees left thoracic scoliosis was noted in association with a sclerotic process involving the inferior portion of the vertebral body of T7 and the superior margin of T8 across a well maintained disk space. Open biopsy confirmed the impression of a nidus in the body of T7 which was histologically consistent with osteoid osteoma. The disk space was well maintained and the sclerotic changes in the superior margin of T8 appeared to represent reactive change. Postoperative relief of back pain was complete. The occurrence of reactive bone across an intact disk space in response to an osteoid osteoma nidus is unique to this case. Osteoid osteoma should be included in the differential diagnosis of chronic spine pain and reactive changes secondary to irritant property of the nidus may be widespread.


Neurotrophic arthropathy of the shoulder secondary to tuberculous arachnoiditis: a case report.

A rapidly progressive neurotrophic arthropathy of the shoulder was noted in a 44-year-old man with tuberculous adhesive arachnoiditis. Difficulty in making the diagnosis of adhesive arachnoiditis was encountered because of the variable and confusing neurologic manifestations until a cisternal myelogram was performed and this previously unreported relationship established.


Calcifying tendinitis: a new concept of its pathogenesis.

To elucidate the pathogenesis of calcifying tendinitis, clinical and morphological investigations were done on 46 surgically treated cases. Contrary to the prevalent concept of degeneration preceding dystrophic calcification, we found no evidence for an active or a healed degenerative process. The affected tendon was transformed into fibrocartilage with a predilection for calcification. The formative phase of calcification was followed in course of time by a resorptive phase during which the deposits were surrounded by phagocytosing cells. There was a concomitant proliferation of vascular channels. We found a significant correlation between severe pain and histological signs of resorption. The pathogenetic mechanism of calcifying tendinitis should be reassessed as a unique disorder of the musculotendinous cuff.


Keratoacanthoma: an unusual hand tumor.

Keratoacanthoma is a common skin lesion of the head and neck, and is well described in the literature. It seldom presents to the Orthopedic surgeon as a hand tumor. The lesion does not require radical approach, but mimics squamous cell carcinoma which usually does. The clinical behavior and pathology, as well as the biological behavior of the tumor, are discussed. Fifteen cases treated by the authors are reported and their clinical and pathological course and treatment are discussed. Serious errors in treatment may arise from reliance on the histologic characteristics alone. Conservative treatment of keratoacanthoma should be avoided but radical excision of the part is unnecessary. Prompt and total excision is the treatment of choice, with closure either primarily or with split skin graft.


Bilateral carpal tunnel syndrome secondary to gouty tenosynovitis: a case report.

A 30-year-old patient developed bilateral carpal tunnel syndrome secondary to gouty tenosynovitis. Relief of symptoms followed removal of the tophaceous masses from the carpal tunnel. Surgical treatment is recommended whenever there is symptomatic median nerve compression.


The Milwaukee brace in idiopathic scoliosis: evaluation of 123 completed cases.

The Milwaukee Brace, as evaluated in 123 completed cases, is effective in controlling and correcting mild to moderate idiopathic scoliotic curves. The factors contributing to more correction include dorsal location, younger patients at onset of treatment, more flexible curves, and most important cooperative patients and parents. Less severe curves also achieved greater correction. Loss of correction after brace discontinuance is negligible, due to the fact that weaning and discontinuance were based on the stability of correction after 24 unbraced hours. Patients cooperative with the wearing and exercise program can expect approximately 25 per cent correction in dorsal curves and 20 per cent correction in lumbar curves. Cosmetic improvement can be expected in the majority of patients. Complications are negligible.


Vertebral body osteomyelitis: spectrum and natural history. A retrospective analysis of 37 cases.

There has been a definite change in the natural history of vertebral osteomyelitis. At the turn of the century the disease was most often seen in younger people, accompanied by a high incidence of abscess formation and associated with a high mortality rate. Today the disease is more commonly seen in the older age groups and is only occasionally characterized by abscess formation. In addition it tends to be of a lower grade inflammatory reaction and has a better prognosis. A urinary tract infection is a common pre-existing condition. Diagnosis may be difficult particularly before the onset of destructive changes radiologically at 8 to 12 weeks. Biopsy by either open or closed methods might be necessary to establishe the diagnosis and isolate the causative organism which is usually Staphylococcus aureus. Epidural infection is the most devastating complication, particularly if neglected. The duration of treatment is determined by following the clinical symptoms, sedimentation rate, temperature curve and interval radiological changes. The prognosis is good and most patients will recover within one year.


Anatomical and functional considerations in total claviclectomy.

There should be no hesitation in performing a total claviclectomy. It is the treatment of choice in cases of ch. pyogenic osteomyelitis of the clavicle and other lesions which demand sacrificing the bone. There was no functional impairment of the shoulder joint or the girdle. There is usually no major postoperative complication and no residual disability. In children, regeneration of bone takes place from the periosteal tube.


Posterior roentgenogram of the foot.

A present there is no reliable way to define the position of the heel in relationship to the tibia during weight bearing. Many surgical and nonsurgical procedures are done to correct a varus or valgus heel without a standard method to define the problem or measure the results. This is a report on a posterior roentgenographic technique which defines the position of the heel with respect to the talus, tibia, and forefoot. This technique allows for measurement of the position of the heel and can be performed in any X-ray facility.


Acidic lipids associated with the local mechanism of calcificaiton: a review.

Two current areas of research on hard tissues have focused upon acidic lipids associated with the local mechanism of calcification and the presence of matrix vesicles as the loci for initial mineralization. Data which show that acidic phospholipids are a component of the vesicle membrane provide a common denominator between these two areas. Furthermore, studies on vertebrate, microbial and synthetic lipoprotein calcification indicate that acidic phospholipids play a pivotal role in the local mechanism. Through a sequence of initial Ca2++ binding followed by desolvation and ion concentration, the acidic phospholipid rich membrane provides an environment in which calcification can be facilitated. A proposed mechanism includes in additon to Ca2++ binding, the formation of (CaHPO4)2 dimers and their condensation into a Ca9 (PO4)6 unit bound to the membrane. The bound unit functions as a nucleus for the formation of additonal units to form an amorphous calcium phosphate cluster. Conversion to crystalline apatite would require dehydration of the environment, either by mineral build up exceeding the hydrophobic domain or by breakdown of the membrane.


Intravenous regional anesthesia for closed treatment of fractures and dislocations of the upper extremities.

Intravenous regional anesthesia for the treatment of fractures and dislocations of the upper extremity is a very effective, consistent and safe form of analgesia which requires low doses of lidocaine and can be performed in an emergency room using a regular blood pressure cuff. Dosage should be related to body weight and the blood pressure cuff should be maintained at higher than systolic pressure for a minimum of 15 minutes after the lidocaine is injected. Release of the tourniquet should be staged as described. Ninety-one per cent of 77 patients had excellent analgesia following the IVRA. Eight per cent had fair results, but this was still adequate to perform the reduction with only minimal but definite discomfort to the patient. Only one patient failed to respond to the IVRA technique. Other advantages such as muscle relaxation during the anesthetic and rapid full return of sensation after cuff release, permit ease of reducion and early anticipation of cast discomfort or pressure pain from sharp edges of plaster. Unpleasant long term side effects of axillary block anesthesia, such as persistent paresthesia have not been seen.


The effect of thyroparathyroidectomy: development of disuse osteoporosis in adult rats.

The present investigation was undertaken in order to study the role played by the thyroid and the parathyroid glands in the development of osteoporosis induced by immobilization. One hundred and fifty-three male adult Sprague-Dawley rats were divided into 2 groups. The animals of one group were thyroparathyroidectomized; those of the other group were left intact. Each group was then divided into two subgroups in one of which the right hind leg of the animals were immobilized by elastic adhesive bandages. The animals were observed for varying periods of time up to 16 weeks. Bone mass and composition was determined and the results indicated that disuse osteoporosis occurs in rats in the virtual absence of the thyroid and parathyroid glands. The bone loss of the immobilized femur and tibia is however less pronounced in thyroparathyroidectomized than in intact rats.


Calcitonin and the bone fluid compartment: effect of calcitonin and/or parathyroid hormone on plasma radiocalcium changes.

Changes in plasma calcium and 45Ca concentrations were followed after injection of calcitonin or a combination of calcitonin (CT) and parathyroid hormone (PTH) into thyroparathyroidectomized rats maintained on thyroxine. Comparison was made between rats injected with the hormone(s) after a recent feeding and after an overnight fast. Also cor (18 hr 45Ca) before, and more than 6 days (greater than 6 day 45Ca) prior to hormone administration. The following results were obtained: The action of CT predominated over that of PTH for the first few hours after injection. However, the effects of PTH were eventually manifested even when additional CT was administered. In the "greater than 6 day" 45Ca groups, PTH normally produced an increase in plasma 45Ca specific activity. However, in fasted rats, plasms 45Ca fell with total calcium with no change in specific activity following CT injection. In fed rats CT injection was followed by a decrease in plasma 45Ca specific activity. When both hormones were administered plasma 45Ca specific activity changes mimicked those produced by CT alone even after PTH plasma effects were manifested. In the "18 hr" 45Ca groups, CT produced first a drop in plasma 45Ca, followed by a reduction in the rate of its removal from plasma. It is concluded that the data can best be explained by the postulate that plasma calcium concentrations are maintained by the control of fluxes between bone fluid in the osteocyte-lining cell bone unit and the extracellular fluid. PTH increases the efflux from this bone fluid compartment while CT restricuts the source of calcium and, therefore, the efflux. Plasma 45Ca changes are due to a combination of changes in flux rates and mixing processes between the extracellular fluid compartment and the bone fluid compartment.


Anterior tibial compartment syndrome associated with ergotamine ingestion.

This is the first reported case of acute anterior tibial compartment syndrome following ergotamine tartrate overdosage. A 25-year-old man developed signs and symptoms of ergotism after ingestion of 72 mg of ergotamine tartrate over the 12 days prior to his hospital admission. On the fourth hospital day, the patient developed bilateral anterior tibial compartment syndrome. The development of this syndrome is postulated to have been due to the progressive edema and tissue pressure in the anterior tibial compartments, worsened by the gradual improvement of the peripheral circulation which followed the diminished vasopastic effect of the ergotamine.


Fractures and dislocations involving the navicular-lunate axis.

This is a report of experience with 48 carpal disruptions including anterior dislocations of the lunate, transnavicular perilunate and perilunate dislocations and subluxation of the navicular. The correct radiographic diagnosis is absolutely essential for effective treatment. Many of these injuries may be treated by closed reduction, but open reduction of transnavicular perilunate dislocations is the procedure of choice. Avascular necrosis of the lunate may follow open dislocation. Primary subluxation of the navicular may occur without dislocation of the lunate.


Reconstruction of the posterior cruciate ligament: preliminary report of a new procedure.

The integrity of the posterior cruciate ligament is necessary for the stability of the knee. The popliteus tendon is a promising, practical, and anatomical donor for reconstructing the posterior cruciate ligament. The procedure can be performed relatively easily using a posterolateral Henderson incision in association with the standard anteromedial parapatellar approach. We have performed the operation in 2 patients, produced good results at 4 and 6 month follow-up examination.


End result observations of X plate compression fixation. A critical review and analysis and a discussion of unsolved problems.

The X plate method of treatment of a diaphyseal fracture employs te internal, cortical and extramedullary compression-fixation of a shaft fracture, using a steel plate device of two components. Four wedges of the X device force the surfaces of the fracture against each other at the same time as the plate is pressed against the cortical surfaces of the reduced fracture fragments. The two components of the device are finally made to interlock firmly. Screws are not used. Plate onlay force and fracture compression force are created by the purchasing of the wedges against the rims of exactly predrilled cortical bores of the fracture fragments. A drill guide, and a device that permits pre-compression and temporary fixation of the fracture fragments are used when drilling is performed. Successvie designs of the employed X devices and auxiliary instruments are described. Clinical experience of the method so far has been satisfactory. Twenty-six forearm shaft fractures and two osteotomies of malunited shaft fractures have been successfuly treated. Present problems are related to the possible need of an implant material of a more springy character tan that of the 2353 (316L) steel implant, used at present and also to reduce the manufacturing costs.


Fatigue fractures of tibial and femoral shaft in soldiers.

In 136 fatigue fractures in military recruits, 58 were in the femoral shaft and 43 were in the tibia. Fatigue fractures in the long bones of the lower limb can be classified on the extend of the periosteal reaction. Most were grade 1, showing periosteal reaction only on one or two cortices as seen on the anteroposterior and lateral projections of the roentgenograms. Physical activity was discontinued immediately when fatigue fracture of the femur or tibia was suspected on clinical grounds alone. Early clinical diagnosis the long bone fatigue fractures in all patients except one. The injured soldiers were ambulatory without plaster cast immobilization or crutches. The suggested classification was used to select patients with Grade 1 fatigue fracture for early resumption of active military training.


Lateral oblique incision for the Charnley low friction arthroplasty.

An oblique incision of the lateral exposure improves access to the acetabulum.


Tibial rotational osteotomy.

Accurate rotational osteotomy is especially difficult in a triangular bone such as the tibia. A technique using a fibular graft to locate the center of rotation and provide stability has been used in 9 operations with very satisfying results. Average healing time was 7 1/2 weeks. A protractor has been designed to measure the degrees of rotation.


Clinical test for anterolateral rotary instability of the knee.

A simplified test for anterolateral rotary subluxation of the knee is largely based on the concepts described by Galway and McIntosh although performed in a different manner. The examiner places the right hand gently on the lateral side of the knee with the thumb overlying the posterior aspect of the fibula and the index finger palpating the anterolateral aspect of the joint line to determine the the tibiofemoral relationship. The left hand embraces the lateral side of the distal end of the femur with the thumb over the posterior aspect of the lateral femoral condyle. With equal pressure on the lateral femoral condyle and fibular head the knee is pushed gently forward into flexion. When anterointernal tibial luxation is present, a reduction phenomenon is felt as the knee passes into the 25 to 40 degree flexion range. This may occur as a sudden palpable and occasionally audible repositioning which is responsible for  such terminology as a "pivot shift" or "jerk sign." We have experienced many instances where the reduction phenomenon is more subtle and is determined by palpation alone. The pathologic mechanics are determined by observations at surgery in 45 patients with a positive test. This test has improved our diagnositc ability and is easly taught to those unfamiliar with knee joint disorders.


Pathology of the limbus in untreated teratologic congenital dislocation of the hip. A case report of a ten-month-old- infant.

A dislocated hip in a 10-month-old infant with multiple congenital anomalies was examined postmortem. The true acetabulum was filled with areolar tissue and the acetabular articular cartilage was covered by fibrous pannus. The secondary acetabulum consisted of fibrous capsular tissue lined by synovial cells. A lip of new fibrous tissue, the limbus, grew over the cartilaginous labrum of the true acetabulum in juxtaposition to the dislocated femoral head.


Dynamic fibular function: a new concept.

Fibular function has long been a point of controversy in the literature. Until recently the fibula's role during gait has been thought of as entirely static. A review of the literature reveals an important dynamic function for the fibula in maintaining ankle mortise stability during weight bearing. Roentgenographic and anatomical studies confirm the hypothesis of progressive distal fibular descent. A taut interosseous membrane and deepened mortise result when be flexors of the foot contract during stance phase. Congenital deformities of the ankle may stem from aberration in the dynamic role of the fibula. Stress fractures and problems resulting from impaired distal migration and synostosis formation are interpreted as disorders of the dynamic role of the fibula.


Morphology of untreated bilateral congenital dislocation of the hips in a seventy-four-year-old man.

Two untreated completely dislocated hips were examined pathologically in a 74-year-old male dissecting room cadaver. The femoral heads bilaterally were 9 cm above the acetabular fossae. They lay adjacent to each ilium with no secondary acetabulum formation. A thickened and markedly elongated fibrous capsule appeared to be the major structure that had checked further migration of the femoral heads during weight-bearing. The femoral heads, although slightly flattened medially and somewhat smaller in size than in the normal adult, showed no degenerative arthritis. Dysplastic acetabular fossae were filled with soft tissue. Bone-to-bone contact with secondary degenerative changes was present only where the femurs, at the level of the lesser trochanters, rubbed against the overhanging superior acetabular rims.


Congenital kyphoscoliosis with paralysis following hemivertebra excision.

This is a case report of a 13-year-old girl with a severely progressive congenital kyphoscoliosis, treated by halo-femoral traction and a single stage anterior and posterior hemivertebra excision. Forty-eight hours after surgery she developed paralysis of bowel, bladder and all motor function with partial preservation of deep sensation only. She began to have neurologic recovery 2 months later with gradual return of a completely normal neurological status over a period of 12 months. Pseudarthrosis and loss of correction of the original deformity required a second major anterior spine fusion 16 months after the initial procedure. No neurologic problems occurred following the second anterior fusion. A stable correction  was ultimately achieved. The mechanism of postoperative paralysis is unknown.


Orthopedic manpower.

Key statistical information regarding Orthopedic Manpower is present to make orthopedists aware of the detailed information that is currently available. It is clear there is still insufficient data to justify radically altering the numbers or types of practices. Until the scope of orthopedic practice is more clearly defined and generally accepted (by orthopedists, other physicians, health professionals and the public) we must continue to monitor our activities and make adjustments through evolutionary changes rather than revolutionary regulations. Quite clearly there are segments of our country that are orthopedically underserved. Thus, it is vital that we seek new methods to encourage orthopedists to settle in these areas. Clearly, the simple production of more orthopedists in the traditional model will not answer the geographic maldistribution. With the tremendous scope of problems cared for by orthopedists, there does not appear to be an oversupply; however, we are headed in that direction. If we continue to rate operative procedures as the most significant and satisfying aspect of the practice, we certainly have enough, but they are not spread across the country in a uniform manner. Significant increases in numbers will be necessary if the orthopedist is to assume the role of general practitioner of the musculoskeletal system as well as a specialist for diagnosing and treating the more complicated musculoskeletal problems (whether by medical-surgical or physical-medical modalities). Should this be the case adjustments must be made in the selection process of orthopedic residents, in training programs, as well as estimates of the numbers of such specialists necessary for the future.


Cylindrical total ankle joint replacement: surgical and biomechanical rationale.

Incongruent designs of total ankle arthroplasty are all unsatisfactory owing to inherently poor wear, deformation resistance, and poor stability. Several congruent designs are capable of providing good function. It is concluded that a cylindrical surface with a horizontal axis located at the center of curvature of the lateral border of the talar dome seems most desirable where adequate subtalar motion is present and a spherical type seems most desirable where such motion is not present. The "New Jersey" cylindrical total ankle arthroplasty using a cylindrical surface uses an ultrahigh molecular weight polyethylene talar component and a mortised cobalt-chromium alloy tibial component both stabilized with methylmethacrylate bone cement and dual fixation fins.


Arthrodesis of the ankle joint with complete removal of the distal part of the fibula: experience with the transfibular approach and three different types of fixation.

In 20 patients the following 3 techniques have been used for ankle fusion, all with a lateral transfibular approach: (1) fibular grafting; (2) lateral removal of the distal fibula and fixation with 3 Blount staples; (3) removal of the distal fibular and fixation with Charnley compression clamps. The compression technique, through a lateral approach, was found to be superior as it avoids section of tendons. Removal of the distal portion of the fibular eliminates the risk of drainage and problems with wound healing due to the presence of a large bone graft immediately underneath the skin. Fusion is obtained more rapidly with the third than the first and second techniques. Pain seems to be related to osteoarthritis of the surrounding joints. The gait pattern depends not only on pain, but also on the position of the foot and on the posterior displacement of the talus. Less osteoarthritis as a result of shorter immoblizaition is the most favorable factor, notwithstanding the longer preoperative period in the third than in the first two methods.


Solitary bone cyst of the cervical spine.

A histologically proven case of solitary bone cyst of a cervical vertebral body seems not to have been previously reported. Cysts of sufficient size to be a potential source of pathologic fracture should be excised and filled with autologous bone grafts.


Late instability in cervical spine fractures secondary to laminectomy.

Of 256 patients with a major spinal cord injury as a result of fracture of the cervical spine, 38 per cent had a laminectomy. Three months after injury, 33 per cent of the patients with laminectomy  required fusion for instability compared to 22 per cent of the nonlaminectomy group. There were no cases of late instability in pure flexion or extension fracture groups. Ninety per cent of the late instability cases were in the groups with hyperflexion and flexion compression fractures. Laminectomy should be avoided for these fractures, but early fusion may be necessary to prevent progressive deformity.


Spinal tuberculosis treated by antituberculous chemotherapy and radical operation.

Between 1956 and 1968, 208 patients with spinal tuberculosis healed by chemotherapy with and without surgical intervention. Two vertebral bodies were affected in 82 patients, one in 23 cases, more than 4 in 70 patients. Sixty-one patients had neural involvement at the time of admission, 42 of them an incomplete or complete paraplegia. All patients were treated by triple-drug chemotherapy. Chemotherapy and bed rest alone was sufficient for 76 patients. Surgical intervention was indicated in 132 cases. Debridement was carried out in 33 cases, debridement and spinal fusion was performed in 18 cases, anterolateral decompression of the spinal cord alone was employed in 15 cases, and together with spinal fusion recommended in 15 cases. Minor surgical procedures were made necessary in 8 cases. The indications for surgery were: (1) unfavorable response to conservative treatment during 3 months, (2) Pott's paraplegia showing no signs of recovery by conservative treatment, (3) Pott's paraplegia developing during conservative treatment (4) cases with unstable spinal lesions, and (5) cases with paravertebral abscesses and sinuses. Complete or good recovery occurred in 61 out of 76 conservatively treated patients. Forty-two out of 61 patients with neural involvement made a complete or a good recovery, 31 being patients with paraplegia. No improvement was noted in 16 cases with neural involvement, and 2 had progression of the neurological signs. A complete recovery was noted in 101 out of 132 operatively treated patients, a good recovery in 21, and no improvement in 9 patients with paraplegia. One patient died; 141 patients returned to their former work, 30 of whom were recovered paraplegics. Fifteen had retired because of advanced age. Modern treatment begins with triple-drug chemotherapy and bed rest for 3 months. If the response is unsatisfactory, debridement or debridement with spinal fusion is carried out as soon as possible. Anterolateral decompression is applied in cases with paraplegia.


Facetectomy for the relief of intraforaminal compression of the fifth lumbar root at the collapsed lumbosacral disk.

This paper presents a long-term follow-up of 23 patients with collapsed lumbosacral disks showing evidence of fifth lumbar root compression treated by facetectomy without fusion. Fifth lumbar root compression is usually caused by protrusion of the fourth lumbar disk. If this is not present the fifth lumbar root will almost invariably be found to be impinged upon laterally in the foramen by one of several mechanisms, which are detailed in this paper. Decompression of the roots at the fifth lumbar foramen may be done by either unilateral or bilateral facetectomy depending upon whether the symptoms are unilateral or bilateral. There has been no forward displacement with unilateral facetectomy and only slight forward movement of the fifth lumbar vertebrae on the sacrum with bilateral facetectomy. There has been good relief of symptoms in most patients. Arthrodesis, as a rule, is not necessary.


Congenital absence of the pectoral muscles. A review of twenty-five patients.

Twenty-five patients with unilateral partial absence of the pectoral major muscle were reviewed to determine the presence of fetal insult, associated anomalies, neoplasia, and prognosis. Fifteen had ipsilateral synbrachydactyly (the Poland Anomaly) which varied in severity from minimal findings to nearly complete absence of the hand. The pattern of abnormality was remarkably uniform with maximal involvement of the midhand and least involvement of the thumb and small finger. The etiology of this condition remains unknown although fetal insult is suggested in some cases. Although reports in the literature suggest a relationship with childhood leukemia, no malignancies were found in these children. None was found to have serious associated anomalies and all were judged to be of normal intelligence, suggesting a generally good prognosis.


Slipped capital femoral epiphysis. A study of 68 cases in the eastern half area of Japan.

Slipped capital femoral epiphysis is an uncommon disease among children in Japan. Eighty-one hips in 68 patients collected in the eastern half area of Japan were examined and studies in reference to the incidence, clinical characteristics, and results of treatment. The estimated yearly incidence rate in boys was 0.3 to 0.5 per 100,000 in the population between 10 and 14 years old. The higher incidence of boys (a 5.8 to 1 predilection for males) was characteristic. The disease was extremely rare in girls. Although Japanese children are generally neither as tall nor as heavy as Americans or Europeans, these patients were relatively taller and also much heavier than average. One of the reasons why children of Japan are not susceptible to slipped epiphysis may be explained by the Japanese physique. Satisfactory results were found in less than half the cases. Poor results were mainly caused by complications such as avascular necrosis and acute cartilage necrosis. The incidence of the latter complication was 20.7 per cent in 58 hips followed longer than a year and a half. The method of treatment seems not necessarily related to the development of chondrolysis. This complication is caused by an unknown genetic factor.


Congenital dislocation of the patella.

In 8 congenital patellar dislocations, in 7 patients, the patella was permanently and laterally dislocated, and irreducible or difficult to reduce. The patella usually was hypoplastic and showed absent facets. The intercondylar groove of the femur also was underdeveloped. In all but one patient, knee function was improved by a surgical procudure which involved lateral release of ptella, medial transpositon of patellar tendon, and plication of medial capsule or advancement of vastus medialis.


Cast brace treatment of plateau and bicondylar fractures of the proximal tibia.

Twenty-nine patients with 30 intraarticular proximal tibial fractures were treated with early application of a cast brace. All fractures united, knee motion was excellent or good in all but one patient. The fracture fragments did not lose position after cast brace application. Varus or valgus deformities could be corrected and maintained. Ninety per cent had no pain at follow-up. Hospital stay was as short as two days and generally under two weeks.


The normal carrying angle of the elbow. A radiographic study of 422 patients.

A radiographic study of the carrying angle in 422 patients demonstrated that the carrying angle increased with age, but there were no real differences in males and females. Apparent differences may be explained by increased joint laxity in females, permitting a greater degree of extension.


Screw fixation of the olecranon after fracture or osteotomy.

For 10 years prior to the availability of the Olecranon Screw described in this article, oblique fixation using a regular Sherman bone screw was employed for displaced fractures (with a suitable fragment) by engaging the anterior ulnar cortex. Internal fixation was supplemented by a split for 3 weeks. The reason for a special olecranon screw is to eliminate the necessity for additional fixation and permit early motion. No instance of non-union or important restriction of motion or serious complication has been encountered.


Clinical features and treatment of joint dislocations in Larsen's syndrome. Report of three cases in one family.

Of 3 cases of Larsen's syndrome in one family, one had bilateral dislocation of the hip and the knee joints. The knee joint was not reduced by manipulation and corrective cast, while both hip and knee joints were simultaneously reduced by skeletal traction of the tibia at the age of 4 months, and the course was satisfactory. Reduction of joint dislocations should be attempted by a conservative method such as skeletal traction as early as possible. Various radiographic skeletal abnormalities occurred in all 3 cases. Larsen's syndrome very likely has a genetic origin.


Osteogenetic epithelial-mesenchymal cell interactions.

FL, HeLa and other non-murine epithelial cells are capable of inducing chondroosseous differentiation when brought into contact with mouse thigh mesenchymal cells. Immunosuppression as produced by cortisone or mouse antilymphocyte serum is required to prevent rejection and to allow growth of the foreign epithelial cells. Cartilage appears within 7 days and bone within 9 days following epithelial cell injection. Electron microscopic studies indicate that the induced cartilage and bone is normal in basic strucutre, and that calcification is mediated by extracellular matrix vesicles. Various forms of mechanical and chemical injury have consistently failed to stimulate cartilage or bone formation in the mouse thigh. Explantation of preosseous thigh tumors to mouse brain allows continued growth of human and mouse cells with development of cartilage or bone in 67 per cent of implants. Microscopy indicates cartilage and bone formation by many mesenchymal cells which are not in direct contact with epithelium. To account for this, two mechanisms of bone induction are envisioned: (1) short-range diffusion of inductive substance(s) and/or (2) transfer of the inductive stimulus by direct surface contact from epithelial cell to mesenchymal cell to mesenchymal cell and so on.


The effects of hyperoxia upon bone in organ culture.

Hyperoxia has been reported to stimulate both resorption and synthesis of bone in vitro. The effects of increased oxygen tension were re-investigated using calvaria from infant mice maintained in a stationary grid culture system for 48 48 hours with an unsupplemented chemically defined medium. Resting resorption due to osteoclastic activity was demonstrated in the explants in air by Von Kossa staining, histology, and 45 Ca release. Resorption was inhibited by exposure to 95 per cent oxygen or hyperbaric oxygenation at 2 atmospheres pressure. Hyperoxia also depressed new bone formatin by osteoblasts although the production of a new collagen, as measured by the incorporation of 3H-proline, was greater in calvaria cultured in hyperbaric oxygen than in paired explants in 95 per cent oxygen. Thus hyperoxia was toxic for both synthetic and resorptive activity of bone cells; these effects may stem from the loss of vital factors present in natural MEDIA supplements.


The anatomy and pathology of congenital dislocation of the hip.

At least 1 per cent of all newborn infants in the United Kingdom have CDH (Fig 10). Among these infants, approximately 85 per cent are normally formed and 15 per cent malformed. Among the normally formed infants, 90 per cent of the CDH are of the Grade 1 type, and 10 per cent of Grades 2 and 3. Such infants have a perinatal mortality of about 5 per cent. In contrast, among the malformed infants, about 50 per cent are CDH Grade 1, and 50 per cent Grades 2 and 3; their perinatal mortality is around 70 per cent. In other words, a much higher proportion than usual of the severe grades of CDH are found among the infants with a high perinatal mortality.


Pathological human synovial fluids. Viscosity and boundary lubricating properties.

On human synovial fluids obtained during operations from the knee joints of 80 patients with different joing disease, relative viscosity was measured at 3 different shear rates and the boundary lubrication was tested by the coefficient of friction in an artificial rubber/glass system. The results were evaluated in relation to the operative findings. The viscosity showed statistically significant differences between the synovial fluids from the knee joints with rheumatoid arthritis, osteoarthritis, and torn menisci, being lowest in rheumatoid synovial fluid and highest in synovial fluids from knee joints with torn menisci. Correlations were found in the variations in the viscosity and the degree of synovitis. The boundary lubrication also showed different values inrelation to the different diseases. Synovial fluid from knee joints with torn menisci seemed to act as the best lubricant and significantly better than rheumatoid synovial fluid. Variations in the boundary lubrications reflect successive degrees of cartilage degeneration.


Monomer leakage from polymerizing acrylic bone cement. An in vitro study on the influence of speed and duration of mixing, cement volume and surface area.

An in vitro study was dthesigned to measure the effects of variable cement volumes and modified mixing techniques on the monomer leakage after simulated implantation. The cement volume as such was found to be an irrelevant parameter for calculations of the monomer loss from bone cement. The leakage was directly related to the surface area of the cement. Variations in the thickness of the cement mantle from 1 to 5 mm did not affect the leakage. Late cement insertion should reduce the total monomer leakage into the tissues. It is doubtful whether an increased stirring speed during mixing reduces the monomer leakage after implantation.


Effects of laminations and blood entrapment on the strength of acrylic bone cement.

The tensile and shear strengths of surgically mixed acrylic bone cement were measured for intact specimens and for special two-part cylindrical specimens containing single laminations perpendicular to their longitudinal axes. Laminations were formed at times ranging from 3 1/2 to 6 1/2 minutes after initial mixing of the powder and liquid for dry interfaces and for interfaces containing fresh blood at the time of lamination formation. In additon, special tests were conducted to measure the bond strength between freshly mixed and pre-polymerized acrylic. The tensile and shear strengths at the lamination interface decreased significantly when the laminations were formed late in the working life of the acrylic. The presence of blood at the interface further weakened the bond to approximately 25 per cent (tension) and 36 per cent (shear) of the virgin strengths of the material. These results support early acrylic placement with dry surgical fields. The bonding of fresh acrylic to pre-polymerized material was most effective when the material was poured into the mold before dough stage. This technique would have practical application in special cases for re-cementing revision prostheses without removing the old acrylic from within the bone.


Normal values of the hip joint for the evaluation of X-rays in children and adults.

X-ray measurements of the hip joints of children, with special reference to the acetabular index, suggest that the upper standard deviation of normal comprises the borderline to a critical zone where extreme values of normal and pathologic hips were found together. Above the double standard deviation only severe dysplasias were present. Investigations of the shaft-neck angle and the degree of anteversion including the wide standard deviation demonstrate that it is very difficult to determine where these angles become pathologic. It is more important to look for the relationship between femoral head and acetabulum. A new measurement--the Hip Value is based on measurements of the Idelberg- Frank angle, the Wiberg angle and MZ-distance of decentralization. By statistical methods, normal and pathological joints can be separated as follows: in adult Hip Values, between 6 and 15 indicate a normal joint form; values between 16 and 21 indicate a slight deformation and values of 22 and above are indications of a severe deformation, in children in the normal range the Hip Value reaches 14; values of 15 and up are pathological.


Intertrochanteric femoral osteotomy with concentric reduction of the femoral head in treatment of residual congenital acetabular dysplasia.

A method of classification based upon increase of the anteversion and valgus deformity of the upper femur associated with a dysplastic acetabulum and subluxation of the femoral head demonstrates 4 main groups: I or II in patients 1 to 3 years of age; III, patients approximately 2 years of age; IV, patients with absolute contraindication for surgical intervention. The Monticelli technique employs a Kirschner wire for the internal fixation and incorporates it in a hip spica. The results of the surgical treatment are very gratifying when classification and specified indications are correct. In follow-up observations ranging from 3 to 11 years, with an average of 7 years, there were practically no complications other than a few superficial skin infections.


The intertrochanteric osteotomy in the treatment of congenital dysplasia of the hip.

The dysplastic acetabulum develops to normal shape only if the head of the femur is in central position in the articualr cavity correct according to biomechanics of the hip joint. Anterior rotation of the neck of the femur should be reduced operatively to neutral position as soon as possible if joint congruity cannot be achieved by conservative treatment. The indication for an intertrochanteric derotation osteotomy is made in cases demonstrating a roof inclination less than 30 degrees in children age 1 1/2 to three. After the third year of age, the mutual growth-stimulating effect of the  articular bodies is not important enough to be useful in treatment of dysplasia. The femoral osteotomy has to be performed intertrochanterically. If articular congruity cannot be achieved by intertrochanteric osteotomy only, an additional innominate osteotomy of the pelvis is indicated at the same stage. The results of 435 cases demonstrated a good development of the acetabular roof if the intervention was performed early, according to correctly specified indications. In cases with insufficient growth potential of the acetabular roof, resulting in an increased inclination, an additional reconstruction of the acetabular cavity is required.


Congenital hip dysplasia in the light of early and very early diagnosis.

Ortolani summarizes 40 years of experience with about 8,000 children with congenital hip dysplasia, treated from birth or at a very early age. All newborns should be screened and examined for congenital hip dysplasia and this exam should be repeated at one month and again in 3 months. The most reliable sign for the diagnosis of congenital hip dysplasia at birth is the "click" sign. The etiology of congenital hip dysplasia is in a localized fault in embryonic development. The treatment started just as early as the condition was suspected. Surgical treatment is recommended for all complete congenital hip dislocations not amenable to treatment by closed methods.


Combined procedure of open reduction and shortening of the femur in treatment of congenital dislocation of the hips in older children.

A one-stage, combined operative procedure for reduction of congenitally dislocated hips in older children consists of shortening of the femur; open reduction by an inferior approach to the joint; reconstruction of the acetabular roof; correction of anteversion of both the femoral neck and the neck-shaft angle; anterior transposition of the iliopsoas muscle. On 60 hips operated in children, ages 5 to 15 with a follow-up period, ranging from 5 to 9 years, the results were found to be excellent in 3 per cent, good in 60 per cent, fair in 30 per cent, and poor in 7 per cent. The procedure is indicated in children up to the time of early puberty. The primary indication is high bilateral dislocation. In unilateral dislocations some residual leg-length discrepancy frequently occurs. This procedure should be done only by orthopedic surgeons who have special training and experience in the treatment of congenital dislocation of the hip.


Treatment of congenital hip dislocation by muscle release, skeletal traction and closed reduction in older children.

A method of treatment of congenital hip dislocation by preliminary multiple muscle releases around the hip, followed by skeletal traction, is employed for closed reduction and immobilization with long leg cast. In 29 hips treated during the period from 1961 to 1972, the results justify the method for treatment of children 3 to 11 years of age with neglected high posterior congenital hip dislocations. The main prerequisite for the procedure is a fairly well-developed acetabulum.


An evaluation of conservative and operative methods in the treatment of congenital hip dislocation.

An evaluation of different methods of closed reduction of dislocated hips during different periods of time shows that manual reduction and fixation in Lorenz position account for a high rate of avascular necrosis. Even with functional and slow reduction by Pavlik harness and overhead extension, there is still a certain percentage of femoral capital necrosis. The fetal position recommended by Fettweis and Salter seems to reduce the incidence of necrosis. Acetabuloplasty combined with detorsion-varus-ostcotomy provides the means of normalizing a hip joint with a greater degree of success than most other methods.


Overdiagnosis of congenital dislocation of the hip.

In a retrospective study of 548 cases of CDH diagnosed and treated immediately after birth in the city of Malmo, 90 per cent may not have developed manifest dislocation even without treatment when the expected incidence is taken into account. It could, however, be demonstrated from variables such as sex ratio, birth rank, fetal presentation and the size of the capital epiphyses that the entire group indeed had characteristics relating them to CDH. These characteristics were more obvious in coses with a firmly established diagnosis. Cases in whom the diagnosis could not be confirmed radiologically deviated less or not at all from the general population.


Total avascular necrosis of the capital femoral epiphysis in congenital dislocated hips.

Ninety-four hips involved with total avascular necrosis in the treatment of congenital dislocation of the hips were reviewed in a search for etiological factors and effective salvage procedures. Pre-reduction traction and adductor tenotomy did not prevent avascular necrosis. Abduction of the hip in the "frog" position was the incriminating common denominator. This position may cause (1) interference of the blood supply to the femoral head by compression of the medial branch of the deep profundus artery; and (2) pressure on the intraepiphyseal grooves by the glenoid labrum. The containment of the femoral head by acetabuloplasty (preferably) below age 8, followed at a later date (over age 10) by transfer distally of the greater trochanter, with the abductor muscles, offers a satisfactory salvage procedure.


Acetabular growth potential in congenital dislocation of the hip and some factors upon which it may depend.

The factors which determine the rate and amount of acetabular growth in congenital dislocation of the hip are ill-understood. A prospective radiological study has been devised in order to assess the influence of the age of congruity, femoral anteversion and neck/shaft angles on acetabular growth. To be included, the children must have reached at least 8 years of age. Those with associated congenital abnormalities and subluxation were excluded, as were those who had operations for acetabular reconstruction. Seventy-four hips were suitable for analysis, and the age range at follow-up was from 8 to 17 years. The acetabular angle was used as an index of acetabular growth. Measurement of this angle, and the anteversion and neck/shaft angles were made before, and each year after reduction of the hip. Congruity was assessed from a radiograph with the legs in the functional position. A satisfactory acetabulum was obtained in 44 hips and the mean age of congruity was 33 months; the acetabulum was unsatisfactory in 30 hips, with a mean age of congruity of 48 months. Four years is the critical age, for if congruity is obtained later, the risk of producing a moderate or severely dysplastic acetabulum is more than doubled. If congruity is obtained under four years of age, growth of the acetabulum with continue in most patients up to 8 and in some to 11 YEARS OF age; the resulting acetabulum was normal or mildly dysplastic. Fifty-nine per cent of the satisfactory hips at follow-up had a normal anteversion angle, and 6 per cent a normal neck/shaft angle. Correction of these angles by themselves, seems not to be a major importance for promoting acetabular growth.


Accidental iron poisoning in childhood. Six cases including one fatality.

Between 1962 and 1973, six children were admitted to the Massachusetts General Hospital because of accidental iron poisoning. Intoxication was life-threatening in two children whose serum iron concentrations exceeded their iron binding capacities. One of these patients died despite intensive supportive care and desferoxamine therapy. Although iron poisoning appears to be relatively uncommon, it can produce life-threatening and fatal intoxication in children.


Congenital hyperammonemic syndromes.

Urea cycle disorders and other hyperammonemic syndromes should be considered in the differential diagnosis in newborns with a history of severe vomiting, lethargy, and seizures, and in infants with feeding problems, episodic vomiting, and altered consciousness. Although the acute neonatal forms of urea cycle disorders are almost always lethal, several of the subacute forms of hyperammonemic syndromes respond favorably to early treatment.


Digoxin bioavailability: formulations and rates of infusions.

The bioavailability of digoxin (lanoxin) tablets, oral aqueous solution of digoxin, and capsules containing a solution of digoxin was compared with digoxin given intravenously over 1 and 3 hr. The mean peak serum concentration of digoxin after the 1-hr intravenous infusion was 5 ng/ml, after the 3-hr infusion, 3.5 ng/ml, and after the oral solution, 2.0 ng/ml. There was an equivalent bioavailability of the oral solution and reference tablets of digoxin. The digoxin in capsules tended to be better absorbed than the reference tablets. There was 21% more digoxin excreted over 6 days after the 3 hr iv infusion than after the 1 hr iv infusion. This indicates that the calculated bioavailability of an orally administered dose of digoxin may vary with the rapidity of injection of the intravenous standard. It is estimated that an oral tablet of digoxin of 0.5 mg has about the same bioavailability as 0.35 of digoxin given by slow intravenous infusion (or 0.4 mg if calculated against a rapid intravenous injection).


Absolute quinidine bioavailability.

The absolute bioavailability of quinidine was studied in 11 hospitalized patients. A 400-mg dose of quinidine gluconate was administered to each patient by intravenous infusion and as an oral solution. Drug treatments were separated by a 72-hr period. In 8 patients, peak plasma quinidine concentrations were reached in 65 min after the oral dose; in the remaining 3 subjects, peak concentrations were reached later. From the ratio of the total area under the plasma concentration-time curves (AUCoral/AUCir), the absolute bioavailability of quinidine ranged from 44% to 89% (mean, 72). In 8 patients, the ratio of the total amount of quinidine excreted in the urine in 48 hr (AUinfinity oral/AUinfinity ir) indicated that the extent of quinidine bioavailability varied form 47% to 96% (mean, 73). The predicted bioavailability of quindine due to first-pass effects was 76+/-11%. It is concluded that absorption after the oral solution was rapid and that the reduction of quinidine bioavailability was due to first-pass hepatic drug removal.


Transient cardiac arrhythmias after single daily maintenance doses of digoxin.

Ten digitalized patients were monitored for detection of cardiac arrhythmias 0 to 8 hr after daily maintenance dose of digoxin in the fasting state. Transient cardiac arrhythmias attributable to digoxin were seen at 2 to 5 hr in 5 subjects. Initial serum concentrations of digoxin were within standard clinical limits in all subjects, but, higher steady-state levels were present in patients with arrhythmias (1.2 to 1.7 ng/ml) than in the others (0.7 to 1.2 ng/ml). The postadministrative serum peak concentrations were also higher in the patients with arrhythmias.


Pharmacokinetics of naproxen overdoses.

In earlier safety studies, naproxen, 600 mg three times daily, was administered to healthy subject without significant adverse effects. Another study demonstrated that single doses of 500 to 900 mg resulted in accelerated renal clearance and a nonlinear naproxen plasma level response after the higher doses. Our report describes the pharmacokinetics of naproxen when administered in single doses of 1, 2, 3, or 4 gm (up to eight times the clinically effective dose in rheumatoid arthritis) to healthy subjects. An increase in urinary excretion rate and continuation of the previously documented nonlinear plasma level response were observed. There were no signs that capacity to conjugate or to excrete the drug was exceeded. There were no adverse effects.


Relationship between the pharmacokinetics and pharmacodynamics of procainamide.

The kinetics of a measure of pharmcologic effect (prolongation of the QT interval) of procainamide, as well as the kinetics of the plasma concentration, urine excretion, and saliva concentration of the drug were investigated in 14 trials in 4 subjects. A single 500-mg dose was given by rapid intravenous infusion, and frequent subsequent determinations of the above variables were made. A 2-compartment pharmacokinetic model with a third compartment for the saliva was used to fit the plasma, urine, and saliva data simultaneously. Analysis of the data reveals that the kinetics of the drug concentrations in saliva and of the pharmacologic effect are indistinguishable. They both must be considered to be different from those of the drug concentrations in plasma. Thus, in normal individuals under the conditions of this study, saliva concentrations more precisely indicate the time-course of drug at a cardiac site of action, although they do not parallel plasma drug concentrations until 6 hr or more after a rapid intravenous infusion. The following average pharmacokinetic parameters for plasma were found: terminal half-life, 2.9 hr; total clearance, 828 ml/min; renal clearance, 334 ml/min; and steady-state volume of distribution, 180 L. Average distribution pseudoequilbrium half-time (t1/2 alpha) was 5.2 min from an initial volume of distribution of 36.6 L.


Influence of viral hepatitis on the disposition of two compounds with high hepatic clearance: lidocaine and indocyanine green.

The disposition of lidocaine and indocyanine green was studied in 6 individuals during and after recovery from an episode of acute viral hepatitis. Both compounds are highly cleared from the blood by the liver so that clearance of both should be sensitive to changes in hepatic blood flow. During the acute phase of illness, clearance of indocyanine green decreased without apparent change in volume of distribution, whereas clearance of lidocaine, decreased in 4, did not change in 1, and increased in 1 during the acute phase of hepatitis. Volume changes for lidocaine were also variable. We observed no significant correlation between any parameters of lidocaine disposition and any of several tests of liver function or any parameters of indocyanine green disposition. The absence of correlation between pharmacokinetic parameters of the disposition of lidocaine and indocyanine green indicates that the influence of hepatic disease on the hepatic processes that lead to the elimination of each compound is not predictable. No useful clinical correlates are now available by means of which to predict lidocaine disposition in patients with altered hepatic function.


Intrasubject variation of warfarin binding to protein in serum of patients with cardiovascular disease.

A study of 31 patients with cardiovascular disease who were taking warfarin regularly had shown pronounced intersubject differences in serum protein binding of warfarin and a highly significant correlation between the body clearance of warfarin and the free fraction of the drug in serum. Similar observations have been made in experimental animals and are consistent with predictions based on theoretical considerations. The purpose of this investigation was to determine the intrasubject variation in the free fraction of warfarin in serum. Samples of serum were obtained from 23 of the 31 patients previously studied. The time interval between the two studies was 3.4 to 5.7 mo. The daily dose of warfarin had been changed by 10.6% on the average. With two exceptions, there was no change in concurrent medications. The ratio of free fraction values of warfarin in serum, second/first study, was 0.948 +/- 0.297 (mean +/- S.D.), and there was a highly significant correlation (P less than 0.001) between the individual free fraction values in the first and second studies.


Naltrexone: disposition, metabolism, and effects after acute and chronic dosing.

The disposition of naltrexone during acute and chronic administration of 100-mg oral dose was studied in 4 subjects. Following an acute dose the mean (X) peak naltrexone plasma level was 43.6 +/- 29.9 ng/ml at 1 hr and for the major biotransformation product, beta-naltrexol, was 87.2 +/- 25.0 ng/ml at 2 hr. Twenty-four hours after the dose the X levels of naltrexone and beta-naltrexol declined to 2.1 +/- 0.47 and 17.6 +/- 5.0 ng/ml, respectively. Following chronic administration and X peak plasma levels of naltrexone and beta-naltrexol rose to 46.4 +/- 18.5 and 158.4 +/- 89.9 ng/ml at 1 hr, but by 24 hr both compounds declined to levels of the same order as in the acute state at 24 hr. Plasma levels of naltrexone and beta-naltrexol measured 24 hr after the daily doses of naltrexone throughout the study indicated that steady-state equilibrium was rapidly attained and that there was no accumulation of naltrexone and beta naltrexol in the plasma after chronic treatment on 100 mg oral doses. Biexponential kinetics were observed for naltrexone and beta-naltrexol in the first 24 hr. The half-life of naltrexone and beta-naltrexol decreased slightly from the acute to thechronic study from 10.3 +/- 3.3 to 9.7 +/- 1.1 hr and from 12.7 +/- 2.6 to 11.4 +/- 2.0 hr. The plasma levels of naltrexone declined slowly from 24 through 72 hr from 2.4 to 1.7 ng/ml, with an apparent half-life of 96 hr. The renal clearance data indicate that naltrexone is partially reabsorbed while beta naltrexol is actively secreted by the kidney. During acute and chronic naltrexone administration the mean fecal excretion was 2.1% and 3.6% while urinary excretion was 38% and 70% of the dose in a 24-hr period. Opiate antagonism to 25 mg heroin challenges was nearly complete through 48 hr after naltrexone. At 72 hr the objective responses reappeared to a greater extent than the subjective ones. Correlation coefficient (r) between naltrexone plasma levels and opiate antagonism was 0.91 and between individual half-life of naltrexone and opiate antagonism it was 0.99.


The enantiomers of phenprocoumon: pharmacodynamic and pharmacokinetic studies.

The pharmacodynamics and pharmacokinetics of the optical enantiomers of phenprocoumon were studied in 5 normal subjects and compared to the racemic mixture. Each subject received a single oral dose of 0.6 mg/kg of racemic, S(-), and R(+) phenprocoumon. S(-) phenprocoumon was 1.6 to 2.6 times as a potent as R(+) phenprocoumon when the area under the effect/time curve was used to quantify the total anticoagulant effect per dose. Comparing the plasma concentrations that elicited the same anticoagulant effect, S(-) phenprocoumon was 1.5 to 2.5 times as potent as R(+) phenprocoumon. The anticoagulant activity of the racemic mixture was between that of the enantiomers. There was no distinct difference in the rate of elimination between the enantiomers. The apparent volume of distribution and the plasma clearance for S(-) phenprocoumon were less than those for R(+) phenprocoumon. When the binding of the enantiomers to human serum albumin was compared, S(-) phenprocoumon was more highly bound than R(+) phenprocoumon. The protein binding of racemic phenprocoumon was between that of the enantiomers. The results show that S(-) phenprocoumon is more potent anticoagulant than R(+) phenprocoumon and that the pharmacokinetic differences between the enantiomers are due mainly to differences in their distribution.


Paradoxical urinary excretion of D-glucaric acid in acute viral hepatitis.

The urinary excretion of D-glucaric acid and the plasma clearance of antipyrine were estimated during the acute phase of viral hepatitis and again during recovery. The plasma clearance of antipyrine was impaired during the acute stage of hepatitis, while the urinary excretion of D-glucaric acid was paradoxically high. Both parameters returned to normal during recovery. These findings suggest that the use of urinary D-glucaric acid excretion as an index of microsomal enzyme induction is unreliable when there is liver injury.


Factors affecting antipyrine metabolism in West African villagers.

Saliva half-life of antipyrine was studied in 49 healthy Gambians between 20 and 60 yr of age of whom 27 were male (mean age, 44.5) and 22 female (mean age, 39.1). Body wieght, height, ponderal index, albumin, and hemoglobin were moderately reduced compared to accepted normal values. Antipyrine half-life was 13.6 +/- 0.58 (SEM) hr. Multiple regression analysis showed that sex, cola nut consumption, hemoglobin in women, and height in men were statiscally significant independent predictors of antipyrine half-life. Half-life was shorter in women, decreased with an increase in height in men, and was prolonged by cola nut consumption. Half-life in women increased with hemoglobin. These factors explained 36% of the variation and suggest that geographic differences in the environment could be important in drug metabolism in man.


A method for measurement of angiotensin II in tissues and its application to rat kidney.

1. A method for extraction, partial purification and radioimmunoassay of angiotensin II in tissues and application of the method to the kidneys of sodium-deficient rats are described. 2. Angiotensin in acid-ethanol extracts of kidney were adsorbed on to a cation-exchange resin, eluted and further purified with an immobilized angiotensin II antiserum, before radioimmunoassay. 3. Thin-layer chromatography was used, in some experiments, to separate fmol amounts of angiotensin II from its immunoreactive peptide fragments before radioimmunoassay. 4. Angiotensin II-immunoreactive material isolated from rat kidney resembled angiotensin II in many of its physicochemical properties and chromatographic mobility. 5. The concentration of immunoreactive material in kidney greatly exceeded that which could be accounted for by trapped blood and suggests that the peptide may have a local role in the organ.


The absorption of sugars from the human buccal cavity.

1. Certain sugars were transported across the buccal mucosa by a carrier-mediated mechanism. 2. The metabolic loss of sugars from the mouth in a 5 min test period was negligible. 3. The buccal mucosal transport process was stereospecific for D-glucose and L-arabinose. 4. The absorption of D-glucose, galactose and 3-O-methyl-D-glucose was at least partly dependent on the presence of sodium ions in the luminal fluid. 5. The transport of D-glucose, was inhibited by galactose and 3-O-methyl-D-glucose, suggesting at least one common carrier system.


Density-dependence of maximal expiratory flow rates before and after bronchodilators in patients with obstructive airways disease.

1.Gas-density-dependence of maximal expiratory flow rats (V max), defined as the ratio of V max. while breathing helium/oxygen (80:20) to V max. while breathing air at the same lung volume, was examined in relation to other measurements of airways obstruction in patients with obstructive airways disease before and after administration of bronchodilators. 2. Seventeen patients showed a 45% or greater increase in specific conductance (sG aw) after bronchodilator therapy (group A) and thirteen patients demonstrated a lesser response (group B). 3. Before the administration of bronchodilators, the degree of obstruction in two groups was not different as measured by lung volumes, sG aw, forced expiratory volume in 1 s, and flow rates high in the vital capacity; yet the maximal mid-expiratory flow rate and the degree of density-dependence were significantly lower in group B. 4. After bronchodilators, both groups of patients showed significant improvements in sG aw, flow rates and lung volumes. However, group A patients showed a signifcant increase in density-dependence whereas group B patients did not. 5. Increased density-dependence after bronchodilators in the group A patients was associated with an increase in the computed resistance of the upstream segment with air and a decrease in resistance with helium/oxygen. These changes could be explained by a more mouthward of equal pressure points, and therefore a further increase in the relative contribution of the larger density-dependent airways to limitation of flow. 6. The fact that density-dependence was not altered after bronchodilators in the group B patients suggests that the site of limitation of flow did not change appreciably. The shift in the pressure-flow curve for the upstream airways was such that the computed resistance of these airways fell. Thus it appears that the airways comprising the upstream segment were dilated.


Measurement of liver blood flow by means of a single injection of bromosulphthalein, without hepatic venous catheterization.

1. A method is described for the measurement of liver blood flow without hepatic venous catheterization by the injection of the a single dose of bromosulphthalein and the analysis of the graph of the plasma disappearance of the indicator. 2. The rationale of the method was tested in three systems which covered a wide range of flow rates. The first system was a physical model with a haemodialyser in which the calculated flow could be compared with the flow measured directly. The second was in anesthetized dogs, in which the calculated flow was compared with that measured by continuous infusion and hepatic venous catheterization, based on the Fick principle. The third system was in unanaesthetized turkeys, in which metabolism of bromosulphthalein does not occur. The calculated flow was compared with the flow measured simultaneously by the uptake of collodial particles by the Kupffer cells. 3. In all three systems the correspondence between the two methods of measuring liver blood flow was good, the differences between them being not statistically significant. 4. The method has been applied to measurements of liver blood flow in man and animals and gives results comparable with those reported by other workers.


Comparison of renal blood flow and transit times measured by means of 99mTc-labelled erythrocytes and Indocyanine Green in humans with normal and diseased kidneys.

1. In nineteen patients with normal or diseased kidneys, renal blood flow, transit times and vascular volume were determined by means of an indicator-dilution method. Two different indicators, plasma-bound Indocyanine Green (IG) and 99mTc-labelled erythrocytes, were used simultaneously. 2. Comparison of the results indicates that IG slightly overestimates renal blood flow, appearance time, mean transit time and vascular volume, as the erythrocyte/IG ratios averaged 0.972, 0.903, 0.93, and 0.921 respectively. Overestimation of the mean transit time was less apparent when it was prolonged. In patients with reduced renal function, the average blood flow values obtained with the two indicators were in good agreement. 3. It is unlikely that axial streaming of erythrocytes accounts for their shorter mean transit time, because the individual erythrocyte/IG mean transit time ratios were independent of the rate of blood flow and the peripheral packed cell volume. 4. Since the erythrocyte/IG mean transit time ratios correlated significantly with the erythrocyte/IG ratios for appearance time and renal blood flow, the common mechanism leading to a depression of all erythrocyte/IG ratios is presumably extravascular circulation and delayed recovery of a small fraction of IG.


The effect of cellulose phosphate on plasma and urinary magnesium at different levels of parathyroid function in man.

1. Previously published data obtained by magnesium infusion in man were found to conform to a Tm/glomerular filtration rate (GFR) model on the assumption of 80% diffusibility of plasma magnesium. The lower limit of Tm,Mg/GFR was 625 mumol/l. 2. Previously published data concerning the effect of cellulose phosphate on magnesium metabolism in normal subjects, patients with latent hypoparathyroidism and patients with primary hyperparathyroidism were found to conform to the same model, with the same limit for Tm,Mg/GFR for all three levels of parathyroid function. 3. The threshold for magnesium excretion is sharper with less 'splay' than for phosphate, but as for phosophate it is close to the normal blood concentration. 4. Because of the geometrical relationship between different methods of presentation of data, at a constant value for Tm,Mg/GFR changes in magnesium load or in GFR automatically produce changes in fractional magnesium clearance. This is the explanation for the increase in fractional magnesium clearance which occurs which with diminishing renal function. 5. Renal conservation of magnesium is a passive consequence of the fall in plasma magnesium. There was no evidence of augmented tubular reabsorption of magnesium in response to magnesium deprivation in any of the three groups of subjects. 6. The tubular reabsorption of magnesium was not altered detectably by a moderate deficiency or excess of parathyroid hormore. Changes in parathyroid hormone secretion are probably not concerned in normal magnesium homeostasis.


Kinetics of hepatic uptake of unconjugated bilirubin.

1. The uptake of bilirubin was studied in the perfused rat liver by a multiple-indicator dilution technique employing the three-compartment model of Goresky. 2. The kinetics of hepatic bilirubin uptake could be described by the Michaelis-Menten equation. 3. The maximal uptake velocity (V max.) and the apparent half-saturation constant (Km) were 4-4 +/- 0-5 nmol s-1 g-1 of liver and 58 +/- 16 nmol/g of liver respectively, indicating that the hepatic uptake system for bilirubin under normal conditions is operating far below saturation. 4. Sodium taurocholate did not compete with bilirubin for hepatic uptake. 5. These findings are consistent with the concept that carrier-mediated transport is responsible for hepatocellular uptake of bilirubin and that bilirubin and bile acids enter the hepatocyte via separate pathways.


Plasma enteroglucagon and plasma volume change after gastric surgery.

1. The changes in plasma enteroglucagon concentration and plasma volume were measured after oral glucose in sixteen subjects before and forty-eight subjects after operative treatment for benign duodenal ulceration. Truncal vagotomy with a drainage procedure had been performed in sixteen of the postoperative subjects studied, selective vagotomy with a drainage procedure in seventeen, and partial gastrectomy in fifteen. 2. Patients in whom the glucose produced dumping symptoms had significantly greater enteroglucagon concentrations than those who were symptom-free, which confirms the results of a preliminary study. There was a highly significant correlation between the rate of rise of plasma volume. 3. There was no difference in the rate of rise or in peak plasma enteroglucagon and the rate of fall of plasma volume. 3. There was no difference in the rate of rise or in peak plasma enteroglucagon concentration between the groups of patients who had different operative procedures. This suggests that enteroglucagon release is not under vagal influence. 4. There was no apparent relation between the plasma enteroglucagon concentration and the time-interval between the operation and the time of study, which implies that the exaggerated release of enteroglucagon after operation occurs in response to the altered gastric physiology and that there is minimal adaptive change.


The kinetics of efflux of 5,5-dimethyl-2,4-oxazolidinedione (DMO) from the myocardium.

1. The efflux of 14C-labelled 5,5-dimethyl-2,4-oxazolidinedione (DMO) from the myocardium of the rabbit has been studied. The perfusate pH was 7-38. 2. The effluent curve is complex and appears to be the resultant of movement between at least four compartments. 3. The first two probably represent intravascular and extracellular compartments; the last two have smaller rate constants and may represent intracellular spaces. Intracellular pH (pHi) calculated from the effluent curve was 7-23 +/- 0-05. pHi estimated from the steady-state distribution volume of DMO was 7-28 +/- 0-02. The existence of two intracellular compartments suggests that DMO is not homogeneously distrubted in the myocardium. It is suggested that the apparent greater buffering capacity of cardiac than skeletal muscle can be explained by the greater number and volume of mitochondria in the myocardium, compartmentalization of DMO and assumptions inherent in the DMO method for the measurement of pHi.


Bone-resorbing activity in the sera of patients with rheumatoid arthritis.

1. Foetal rat hemi-calvaria were incubated in organ culture with sera from patients with active rheumatoid arthritis. 2. Increased 45Ca resorption was produced by sera from patients who were hypercalcaemic. 3. This bone-resorbing effect could be inhibited by calcitonin.


Relationship of epicardial ST segment elevation to the plasma free fatty acid/albumin ratio during coronary occlusion in dogs.

1. Intravenous infusions of lipid-free albumin were used to lower the arterial non-esterified fatty acids (NEFA)/albumin ratio during coronary occlusion in dogs. 2. Reduction of the NEFA/albumin ratio was accompanied by proportionate reductions in myocardical uptake of NEFA and the degree of ST segment elevation in epicardial electrocardiographic recordings from the ischaemic zone. Aortic pressure and heart rate were unchanged. 3. Infusions of control albumin preparations had no effect on the NEFA/albumin ratio or ST segment elevation. 4. These observations support the proposition that the disturbance of cellular function during myocardial ischaemia is influenced by the degree of saturation of albumin-binding sites with NEFA and by their availability.


How effective is safety packaging?

Of 96 ingestions involving safety packaging, 82% involved misuse. The package in some way was unacceptable to the consumer--it was too difficult to open or too difficult to close. Nonacceptance by the elderly was not a significant factor. In only 18% of the safety packaged ingestions, did the child upen the package. The child was more likely to be able to open the screw-cap and the strip-pack. The pop-off and press-lift were not opened by any child but were types misused only by parents. The older child with a record of prior poisoning was most likely to open a safety package. These children would appear to represent a hard core of risk subjects refractory even to safety packaging. Safety packaging has had a dramatic effect on the morbidity and mortality of accidental poisoning. There are two remaining problems that require further study: 1. The analysis of technical factors impeding consumer acceptance and child proofing. The ideal package is so easily handled by the adult that misuse does not occur, but is too difficult for the child to open. 2. The personality characteristics of the safety-package-resistant child. Safety packaging, as implemented by the Comsumer Product Safety Commission, has had remarkable success. Education did not reduce accidental poisoning; safety packaging does. Pediatricians, pharmacists, and toxicologists must work with industry and the Consumer Product Safety Commission to complete the goal of elimination of accidental poisoning.