Chronic anteromedial instability of the knee. This is a review of 26 patients with 2 or more years of knee pain or giving way or both in whom the most striking clinical finding was moderate or marked anteromedial instability. Of 27 knees, more than 15 responded favorably to a thigh-muscle-strengthening program. The Lenox Hill brace proved to be a useful adjunct in 9 patients.


Bilateral traumatic rupture of the infrapatellar tendon. This is a case report and discussion of the traumatic lesion of bilateral rupture of the infrapatellar tendon in a 52-year-old man. This injury is very rare and seems not to have been previously documented. The treatment consists of surgical repair and cast immobilization. Bilateral rupture of the infrapatellar tendon should be suspected when after injury a patient is unable to actively extend his knee.


The Synovial shelf syndrome.

The Synovial shelf syndrome. A syndrome complex mimicking a tear of the anterior horn of the medial meniscus consists of absence of effusion with negative arthrographic and arthroscopic examinations. Because of a thickened band of the medial synovial shelf this entity is termed the "medial synovial shelf syndrome."


Paget's disease of the patella.

Paget's disease of the patella. Isolated Paget's disease of the patella occurred in a 44-year-old man, and included previously unreported complications of this disorder such as patellofemoral arthritis and elevated serum alkaline phosphatase.


An artificial ankle joint.

An artificial ankle joint. Ankle fusion has been the time-honored treatment for painful debilitating conditions of the ankle due to osteoarthritis and rheumatoid arthritis. It is not a uniformly successful operation and has a high complication rate. If there is pre-existing disease in the knee or midtarsal joints, the pain is frequently made worse by ankle fusion. If there is no pre-existing disease, then painful degenerative changes frequently occur in the midtarsal joints subsequently. An artificial ankle joint has been used successfully since 1973 in patients who otherwise would require ankle fusion. The design of the prosthesis allows unrestricted motion in all planes. It also allows imperfect placement of the device without compromising results. The dome of the talus is not resected during insertion of the prosthesis. Only 1 cm of distal tibia is resected, thus allowing fusion without difficulty should it later become necessary. The superior position of the polyethylene device decreases wear from particulate matter which might settle by gravity. Study of 50 total ankle arthroplasty cases shows that predictably good results can be obtained in ankles with good stability, reasonably normal anatomy, and rheumatoids who are not on long-term steroid therapy.


Surgery of the wrist in rheumatoid arthritis. One hundred four patients with rheumatoid arthritis of the wrist were evaluated a minimum of 12 months post-operatively (average of 34 months). Seventy patients had 87 arthroplasties and 34 patients had 41 arthrodeses performed on the Arthritis Service of Rancho Los Amigos Hospital (Downey, California), from 1962 to 1975. Seventy-eight per cent of the arthrodeses fused, yet only 69% were painfree. Of the 22% that did not fuse, 67% were pain-free. Carpal and/or intercarpal synovitis recurred in 16% of the fused group and 33% of the nonfused group. Eighty-three per cent of the arthroplasties were pain-free, 91% were stable, and all lost motion which averaged 40 degrees (55%). Spontaneous fusion occurred in 16%). Synovitis recurred in 8.0%.


Wrist arthrodesis.

Wrist arthrodesis. Arthrodesis of the wrist is an excellent procedure indicated only in carefully selected and evaluated cases. Eleven patients with various pathological lesions were treated by a modification of standard surgical techniques. Good stability and bone graft placement was secured by an easily removed internal fixation device. External immobilization was required for minimal periods of time. The end results were satisfactory.


The treatment of fracture dislocations of the thoracolumbar spine with halofemoral traction and Harrington rod instrumentation. Although function does not return after complete spinal cord injuries, partial recovery is possible after incomplete lesions Halofemoral traction may produce early decompression of injured neural elements in the spinal canal by anatomic realignment of the spinal column. It also acts to stabilize the very unstable thoracolumbar fracture dislocation and prevent displacement as well as further neurologic trauma. The body jacket is easy to make and apply. It allows early mobilization of patients when utilized in conjunction with the posterior spinal fusion and Harrington rod fixation.


Anterior interosseous nerve entrapment: (Kiloh-Nevin syndrome) report of seven cases. Pain may be the earliest symptom of anterior interosseous nerve entrapment (Kiloh-Nevin syndrome), and seems not to have been described before. The arcuate ligament of Fearn and Goodfellow may entrap the median as well as the anterior interosseous nerves, in which case a patient may have numbness as well as pain. Rheumatoid disease and gouty arthritis may be a predisposing factor in anterior interosseous nerve entrapment.


Fatigue fracture ossa pubes due to obesity. Report of a case. A 60-year-old menopausal woman, who was in otherwise good health, save for morbid obesity, developed fatigue fractures of her ossa pubes, bilaterally, superiority and inferiorly. This type of pathologic fracture seems not to have been reported previously.


Evaluation of the adult forefoot.

Evaluation of the adult forefoot. The evaluation of the forefoot consists of a brief history, a detailed examination, and supplementary tests. Foremost in the history is the chief complaint. The examination includes attention to gait, wear pattern of the shoes, location of tenderness, distribution of calluses, presence of swelling and masses, joint range of motion, changes in the circulatory and neurological systems, and status of the skin and nails. Supplementary studies include standing roentgenograms, blood tests, ankle blood pressure measurement using a Doppler instrument, photographs and footprint impression.


Coagulolysis assay in the detection of deep vein thrombosis in the orthopedic patient. A preliminary report. The recently developed coagulolysis assay was utilized in conjuction with fibrinogen uptake scanning to monitor 91 of 111 consecutive orthopedic patients scheduled for hip surgery or total knee replacement. Sixteen patients had abnormal coagulolysis assays and positive scans. Venography was performed in 15 of these patients, and deep vein thrombosis was documented in 12. Five patients developed pulmonary emboli, including one with negative venogram. Thus, over 80% of the patients in which both the coagulolysis assay and the fibrinogen scan were abnormal had additional documentation of deep vein thrombosis. In 41 patients, the coagulolysis assay was negative. Venograms were not routinely performed in this group. However, 3 patients developed pulmonary emboli indicating that deep vein thrombosis developed in this group. Only one patient had a normal coagulolysis with a positive fibrinogen scan. Venography documented a deep vein thrombosis. Thirty-three patients who had normal coagulolysis assays and negative fibrinogen scans also had no evidence of deep vein thrombosis or pulmonary embolism. The coagulolysis assay appears to be a safe, noninvasive study for the detection of deep vein thrombosis. There was only a one per cent false-negative incidence.


Autoimmunity in degenerative disk disease. A histopathologic study. Recently, on the basis of in vitro experiments, a number of workers have suggested that degenerative disk desease may have an autoimmune basis. In order to corroborate these findings, a histopathologic study was undertaken on 218 specimens. A series of 108 Schmorl's nodes and 110 intervertebral disks obtained at laminectomy were examined for an immune-reaction type of inflammatory cellular infiltrate. While no inflammatory cellular infiltrates were found in any of the specimens, there were granulation tissue ingrowths and vascular invasion. these pathologic findings may represent the body's response to mechanical injury rather than in inflammatory response to a thus far undefined antigen.


X-ray diagnosis of healing fractures in rabbits. Do X-rays adequately reflect the strength of callus post fracture? Eleven rabbit tibiae were manually fractured and allowed to heal in plaster. At varying times post fracture, the rabbits were sacrificed and the tibiae were removed. AP and lateral X-rays of each tibia were obtained and shown to 27 orthopedists and radiologists who were asked to rank the bones in order of strength. The valid ranking was done using data obtained by loading the bones axially to failure in an Instron machine. Each physician's ranking was compared with that obtained from the Instron with a median correlation level p=0.0668. This implies that a physician, whether an orthopedist or radiologist, is not very reliable at determining early osseous union.


The function of the toes in walking, jogging and running. The foot has been studied in walking, running and jogging using high speed cinema photography in the laboratory for gait analysis in the Shriner's Hospital for Crippled Children, San Francisco. During running, as well as in walking, the extrinsic toe flexors restrain progression of the tibia. The extrinsic extensors accelerate the tibia over the fixed foot. The intrinsic toe muscles function from mid-stance to lift-off when the subject runs on his toes. In sprinting, the intrinsics are active throughout the weight-bearing phase.


The effect of a constant direct current on the repair of an experimental osseous defect. To investigate the effect of a constant direct electrical current on the mineral deposition in an experimental osseous defect, 8 microamperes of current were applied across a circular osteotomy placed in the lateral cortex of an avian metatarsus. Mineral deposition was measured to quantitate bone formation in vivo using iodine-125 absorptiometry. The electrical current had no effect either on the initiation or the rate of mineral deposition. However, the quantity of mineralized callus was significantly greater in the treated than untreated bones.


Experimental study on healing of bone fractures using L-dopa. Internal fixation with plate and screws was combined with administration of L-Dopa, which presumably operates by stimulating release of growth hormone. The combination induces osteogenesis, callus formation and complete union in the experimental femur osteotomy gap (10-20 mm long). Complete clinical and radiologic union was achieved in dogs treated for 3-6 weeks, thus achieving healing of a bone gap which otherwise would have formed a pseudarthrosis.


Bioelectric potentials associated with the growing deer antler. Bioelectric potentials associated with the developing deer antler throughout its growth cycle can be correlated with the rate of longitudinal bone growth. Electrodes were connected to a high input impediance microvoltmeter, and potentials on the surface of antlers of mature deer were measured during the antler growth cycle. The reference electrode was placed at the base of the antler, while the recording electrode was placed at the antler tip or along the antler shaft. Antler length measurements were made during the growth cycle and longitudinal growth rates were determined. Growth rates and bioelectric potentials were compared for three specified periods during the antler growth cycle. The most negative potential was recorded from the antler tip. Furthermore, electronegativity increased as the rate of growth in length increased and decreased as the rate of growth in length decreased. The potentials reached isopolarity at the end of antler growth.


Chevron osteotomy for hallux valgus.

Chevron osteotomy for hallux valgus. The chevron osteotomy for realignment of the first metatarsal head in metatarsus primus varus deformity has been utilized at the Mayo Clinic since 1976 on 26 feet (18 patients). Follow-up evaluation disclosed excellent relief of pain, good cosmetic correction, and overall patient satisfaction. Radiographic evaluation demonstrated reduction in the angle between the phalanx and the metatarsal bone of the great toe as well as narrowing of the forefoot with a decreased angle between the first and the second metatarsal bones. The stability of the osteotomy, the technical ease, and the absence of secondary difficulties such as transfer metatarsalgia make this procedure preferable when osteotomy of the distal portion of the first metatarsal bone is used for correction of moderate deformity.


A simple operation for hallux rigidus.

A simple operation for hallux rigidus. Dissatisfaction with the Keller-type operation and the arthrodesis of the first metatarsophalangeal joint in hallux rigidus led to the use of a wedge osteotomy method at the base of the proximal phalanx. Short-term results in 8 patients suggest that further testing of this method should be worthwhile.


Arthrodesis of the first metatarsophalangeal joint for severe bunions and hallux rigidus. Compression arthrodesis of the first metararsophalangeal joint using a modification of the technique of McKeever is described. This operation consistently produces the best results for hallux valgus and hallux rigidus of the great toe. The operation has been found to be applicable where there have been previous attempts at surgical correction. It also produces good results in patients having rheumatoid arthritis when there is minimal involvement of the interphalangeal joint.


Hallux rigidus: A review of the literature and a method of treatment. Twenty patients with hallux rigidus were evaluated following cheilectomy. The surgical procedure involved resection of proliferative bone at the metatarsophalangeal joint to allow at least 45 degrees of passive dorsiflexion. The follow-up ranged from 7 months to 156 months. Postoperatively, there was minimal progression of the degenrative process. Subjectively, there was uniform patient satisfaction with the procedure.


Morton's metatarsalgia in rheumatoid arthritis. Findings in a follow-up study of 66 operations Morton's metatarsalgia performed on 52 patients suffering from rheumatoid arthritis during the years 1954-1977 were in many respects different from those described as "classic" Morton's neuroma. The incidence was one to 520 in rheumatoid patients. The ratio of females to males was 9.4 to one. Histology revealed inflammatory or degenerative changes of the walls of synovial cavities often in connection with typical rheumatoid nudules. The changes of the nerves were non-specific alterations caused by chronic compression. Surgical removal of the tumor-like formations gave uniformly good results. Early metatarsophalangeal synovectomy for rheumatoid arthritis decreased in need of operations for Morton's metatarsalgia from 4.5 to 0.6 operations per year and can be recommended as a prophylactic procedure.


Forces under the hallux valgus foot before and after surgery. Abnormalities in the hallux valgus foot and changes after surgery were investigated by measuring the distribuiion of load on the foot in walking. Hallux valgus was associated with reduced load imposed on the toes, and on the medial side of the forefoot, compared with a large sample of healthy feet. Abnormalities correlated with the degree of the deformity. Both Keller's operation and a wedge displacement osteotomy of the first metatarsal not only failed to restore normal loading but increased the abnormalities of loading seen preoperatively. A large decrease in the angle between first and second metatarsals as a result of surgery minimized this increase. A silastic arthroplasty did not carry high loads when used to treat hallux valgus, but near normal loads were imposed on it when used for hallux rigidus. Considerable variability was found in the loading distribution on the healthy feet. The distribution between first and second metatarsal heads was partially dependent upon their protrusions, relative to the direction of walking. The changes in the relationships between the loadings on the forefoot and skeletal shape in response to surgical operations are important for our understanding of treatment of the hallux valgus foot.


Onychocryptosis: principles of non-operative and operative care. Onychocryptosis has many causal factors which contribute to the impingement of the nail edge with the soft tissue nail wall. The treatment protocol for ingrown toenail includes a regimen of conservative care, nail plate avulsion and nail bed ablation.


Freiberg's infraction: a subchondral bone fatigue fracture. A new surgical treatment. Observations on plantar pressure points suggest that Freiberg's infraction is osteonecrosis of the second or third metatarsal head resulting from a subchrondral bone fatique fracture. A series of 53 cases were successfully treated by deflexion osteotomy of the involved metatarsal head.


Thomas Morton's disease: a nerve entrapment syndrome. A new surgical technique. A new interpretation of the surgical treatment of Morton's neuroma consists of release of the anterior edge of the deep plantar fascia (deep intermetacarpal ligament) without resection of the neuroma. In 206 patients treated with this technique, 83% had rapid and stable improvement. An additional 15% were improved but with some persistence of pain. Division of the ligament without excision of the neuroma provides good pain relief in most patients without the hazards of loss of sensation, loss of sweat production, or neuroma development in the nerve stump.


Splenic visualization in a patient with glucose-6-phosphate dehydrogenase deficiency. A case of splenic visualization of 99mTc-methylene diphosphonate in a patient with G-6PD deficiency who did not show radiographic evidence of splenic calcification is presented and discussed.


Comparison of left ventricular ejection fraction by EKG-gated radionuclide techniques and contrast angiography using a microcomputer system. The left ventricular ejection fractions of 53 patients were determined from multi-image cardiac blood pool scintigrams in the left anterior oblique position utilizing a microcomputer and floppy disc. These data were compared to ejection fractions obtained at cardiac catheterization in the right anterior oblique position. The ejection fraction obtained by radionuclide technique was comparable to that obtained by contrast angiography in the 53 patients with an r = 0.93. Forty-five patients with coronary artery disease showed an r = 0.92. In the coronary artery group with regional wall dysfunction, the correlation was r = 0.89.


Radionuclide blood flow studies before and after gelfoam embolization of intracranial meningiomas. Radionuclide blood flow studies were employed to evaluate the success or failure of preoperative Gelfoam embolization in two patients with intracranial meningiomas. In both cases, the initial radionuclide blood flow study showed tumor visualization during the arterial phase. Immediately following the embolization procedure, the radionuclide blood flow study showed no visualization of the meningioma during the arterial phase, indicating a successful embolization procedure in preparation for removal of the tumor in a relatively bloodless field.


False-positive lung imaging: inadvertent injection into a pulmonary artery catheter. A case of a ventilation-perfusion mismatch seen post-operatively in a patient with chest pain is reported. There was absence of perfusion to the right lung, with relatively normal ventilation. The study was initially interpreted as indicating a high probability of pulmonary embolus. It was then discovered that the injection had been inadvertently made into a Swan-Ganz catheter, with its tip in the left main pulmonary artery. The mismatch was therefore iatrogenic and not related to pulmonary embolus. The false-positive lung imaging which resulted has not been previously reported in the literature.


Pediatric radionuclide ventriculography. Computed tomography is the standard diagnostic examination employed to identify the morbid anatomy of cerebrospinal fluid spaces in children. This noninvasive technique provides excellent anatomic information. However, CT only indirectly characterizes the cerebral spinal fluid pathways. When it is necessary to determine precise bulk cerebrospinal fluid flow for surgical correction, then radionuclide ventriculography (RNV) is a useful adjunctive procedure.


Pseudoaneurysm of the profunda femoris artery diagnosed on angiographic phase of bone scan. A case of post-traumatic aneurysm of the profunda femoris artery following self-administration of an intramuscular injection is reported. The diagnosis was made prior to contrast arteriography on the basis of a radionuclide angiogram performed as part of a bone scan. Additional confirmation was obtained by ultrasound examination.


Right-sided spleen with partial situs inversus of the abdominal viscera: visualization of the spleen by dynamic and static 99mTc-sulfur colloid imaging and 51Cr-labeled red blood cell sequestration imaging. In a patient with right-sided stomach and malrotation of the small bowel and cecum visualized by gastrointestinal x-ray studies using barium, a right-sided spleen was demonstrated by 99mTc-sulfur colloid and 51Cr-labeled red blood cell imaging. The sulfur colloid study also demonstrated that the liver was in its usual right upper quadrant location.


Probe radiocardiography: validation of a technique to routinely determine left ventricular ejection fraction. We investigated the probability of obtaining a valid radiocardiogram with the first commercially available cardiac probe and a peripheral injection of the radiopharmaceutical. Measurements of left ventricular ejection fraction (LVEF) were obtained in a series of 15 patients undergoing cardiac catheterization. Probe LVEF determinations using central, peripheral and rapid sequential injections correlated well with each other and with ventriculography (r = .88--.98). By documenting its accuracy and precision, this study confirms the validity of a new technique for measuring LVEF.


Maternal transport.

Maternal transport. Maternal transport offers the following distinct advantages over newborn transport: 1. The mother at risk may receive the highest level of obstetric expertise and technology available in the area. 2. The newborn is assured of immediate intensive paediatric evaluation and support. 3. The reduced equipment needs increase the speed and efficiency of the transport operation. 4. Mother-infant bonding may be enhanced. Maternal transport can never replace newborn transport for there will always be unexpected deliveries of compromised or malformed infants. Thus, in an effective regional perinatal care system, obstetric and neonatal transport programmes should complement each other. Experience to date would indicate that, when such efforts are co-ordinated, one can expect a further decline in perinatal morbidity and mortality for the region.


Electromechanical intervals of the fetal cardiac cycle. The measurement of electromechanical intervals of the fetal cardiac cycle may be useful in the evaluation of cardiac status, since they are based upon sound physiological principles. Studies of EMIs in the human fetus are currently in their infancy and clinical evaluation of their usefulness awaits the development of adequate data acquisition, reduction and analysis techniques.


Monitoring of uterine activity.

Monitoring of uterine activity. The aim of modern obstetrics is to deliver a healthy, undamaged infant to a healthy, happy mother. The ability to classify and treat abnormalities of uterine activity safely with the plotting of cervical progress against time and to quantitate uterine activity as adequate or inadequate allows for more specific and rapid treatment. Treatment may be instituted more rapidly with monitoring and thus avoid prolonged labours with maternal exhaustion and dehydration. With normal fetal heart rate and variability Schifrin (1974) has stated that the differences in fetal outcome associated with various patterns of abnormal labour essentially disappear if mid-forceps procedures are abandoned and only spontaneous vaginal delivery or caesarean section is used.


Fetal breathing movements: antepartum monitoring of fetal condition. Until recently, the relative inaccessibility of the human fetus to physical assessment has made antepartum assessment of its condition difficult. The development of methods for accurate antepartum fetal heart rate monitoring and the subsequent study of heart rate responses to various stimuli have resulted in a significant improvement in accuracy of antepartum fetal surveillance. The development of real time B-mode ultrasound enables the clinician to assess many additional fetal biophysical variables including fetal breathing movements. In our observations, the combination of heart rate and fetal breathing assessment has produced a significant improvement in differentiating the normal from the compromised fetus. The addition of other biophysical variables (tone, movements and amniotic fluid volume) have further refined the ability to identify the fetus at risk. At this point, we have evaluated only a few of many possible variables. It seems probable that, as other fetal biophysical variables are included with the overall assessment, for example fetal reflexes or fetal biophysical response to exogenous stimuli, the identification of the fetus at risk and the quantitation of the magnitude of risk will become increasingly more precise.


Effect of Position on Blood Pressure in Infants. In order to estimate the effect of position on blood pressure measurements during the first year of life, pressures were recorded for 71 infants at one, three, six and twelve months of age in both the propped and lying positions. The position of the infant appeared to have little effect on mean values or upon the correlation of measurements over time. These results favor the use of a position for blood pressure measurement during infancy which places primary importance upon the comfort of the child.


Safety of intravenous diazoxide in children with severe hypertension. The safety and efficacy of diazoxide administered intravenously in the treatment of children with acute severe hypertension have been evaluated by a collaborative study. Observations of the response of blood pressure in 36 patients, ranging in age from two months to 18 years, during the initial episode of hospitalization reveal diazoxide treatment to be effective in lowering blood pressure in 94 per cent of the cases. No serious adverse circulatory, fluid and electrolyte, metabolic or hematologic effects were observed. Symptomatic and subjective reactions observed with diazoxide administered intravenously to children were identical with those described in adults. Reinstitution of other means of antihypertensive therapy is safe and effective when delayed until the transiently induced period of hypotension has passed. Repeated use of diazoxide for subsequent recurrence of severe hypertension was equally effective and safe in 93 per cent of the instances. The results lead us to recommend the use of intravenous diazoxide for treatment of children with severe symptomatic hypertension especially when it is refractory to control by other hypertensive agents.


Chronic and occult stool retention: a clinical tool for its evaluation in school-aged children. A scoring method was developed to assess severity of stool retention using plain abdominal radiographs. To determine whether the technique was clinically valid in identifying chronic stool retention, the method was used to evaluate films taken of children with known stool retention before and after therapy. The method showed significant statistical differences between symptomatic pre-therapy films and controls and between pre- and post-therapy films of treatment "successes." No significant differences were found between pre- and post-therapy "failures." Use of radiographs is not a substitute for careful history taking and examination, but this scoring method for evaluating stool retention can be recommended prior to more extensive, invasive investigations in children presenting with functional abdominal complaints.


Shwachman-Diamond sydnrome and chronic liver disease. Clinically inapparent persistent chronic liver disease in a 15-month-old male patient with Shwachman-Diamond syndrome is presented. Cryptic hepatic involvement may be an unrecognized feature of the syndrome and should be evaluated in all cases.


Estimation of kinetic parameters from a two-point determination of the drug cumulation factor. A method is described which allows the calculation of kinetic parameters of drugs from two data points, involving a set of simple algebraic equations. This method is based on cumulation characteristics of drugs during multiple dosing. The necessary two blood samples are collected at the end of the first dosing interval and before a succeeding dose after steady state has been reached. The method is applicable for drugs which exhibit linear kinetic characteristics not subject to concentration or time-dependent phenomena. The estimates of the kinetic parameters are associated with different ranges of possible errors, with total clearance being the most reliable estimate. The potential clinical utility of this method is discussed.


Effects of metoprolol on blood pressure and plasma renin activity in thiazide-resistant hypertensive patients. Twenty patients with mild to moderate hypertension whose blood pressures were not adequately controlled by a thiazide diuretic were treated for 4 wk with metropolol. Normotension (diastolic pressure less than 90 mm Hg) or reduction in diastolic pressure of at least 10 mm Hg was achieved in 12 of the patients 1 wk after metoprolol (200 mg/day) was added to the hydrochlorothiazide (100 mg/day) regimen. In  the other 8 patients, pressure reduction was attained with larger doses (300 to 400 mg/day) of metoprolol. After 1 wk of combined therapy, heart rate decreased by 11% (p less than 0.001) and plasma renin activity (PRA) decreased 48% (p less than 0.001). The individual changes in mean blood pressure did not correlate with either the premetoprolol PRA level (r = 0.14) or the changes in PRA after metoprolol (r = 0.03) but did correlate with steady-state metoprolol plasma levels (r = 0.61, p less than 0.01). Pressure and heart rate reductions were sustained during the last 3 wk of combined therapy but the PRA decrease did not persist; levels gradually rose to near control by the fourth week. Urinary sodium excretion was not consistently changed on metoprolol therapy.


Effects of beta blockade with acebutolol on hypertension, hemodynamics, and fluid volume. Eleven patients with essential hypertension were treated with the beta adrenergic blocker, acebutolol. Clinical, systemic, and regional hemodynamic and biochemical studies were performed before and after 4 wk of acebutolol therapy (average doses, 1,200 mg/day.) In 4 patients there was a reduction in mean arterial pressure greater than or equal to 10 mm Hg; there was none in the remainder. Regardless of the blood pressure response, the renin secretory index did not change. Although cardiac output did not change, renal blood flow fell (p less than 0.005) without relation to response of arterial pressure. Supine heart rate decreased (p less than 0.05), so also the responses to upright tilt (p less than 0.01) and isometric exercise (p less than 0.02). These results demonstrate that in those patients with a hypotensive response to acebutolol, the clinical effect was not related to reduced cardiac output or plasma renin activity, further adding to confusion on the mechanism of the lowering of elevated blood pressure by beta adrenergic blockade.


Metabolic changes in muscle on long-term alprenolol therapy. Muscle biopsies from the vastus muscle were taken at rest and immediately after upright bicycle exercise at 50% of the individual VO2max, before and during 6 wk of alprenolol treatment (200 to 400 mg twice daily) in 6 untrained patients with essential hypertension. Resting muscle concentrations (mmole - kg-1 - wet weight) of glycogen, glucose, lactate, and high-energy phosphates [adenosine triphosphate (ATP) and creatine phosphate (CP)] were not affected by alprenolol treatment, but after 10 min after  exercise the glycogenolysis increased and depletion of ATP and CP was enhanced. The relationship between blood and muscle lactate was altered by alprenolol, indicating that alprenolol prevents lactate translocation from the muscle to the blood. The results show that during moderate exercise, leg muscle metabolism is influenced by long-term antihypertensive therapy.


Reduced renovascular resistance by clonidine. The antihypertensive effect of clonidine has been attributed to acute inhibition of sympathetic outflow from the central nervous system. This conclusion is derived from experiments with single doses of clonidine. The mechanism of the long-term blood pressure-lowering effect of clonidine has been less well characterized. Antihypertensive therapy may alter renal hemodynamics and these changes may ultimately affect systemic blood pressure. We studied the effect of long-term clonidine therapy on intrarenal hemodynamics, the renin-angiotensin system, and selected indices of sympathetic nervous system activity in 13 patients with essential hypertension to further elucidate its action. Long-term clonidine therapy resulted in decreased MAP and RVR associated with the suppression of supine but not upright PRA. RPF, RBF, FF, and WBV did not change. UKA, on index of the the putative vasodilating renal kallikrein-kinin system, was also not changed. Our findings suggest a role for PRA in modulating RVR during long-term clonidine therapy. This was associated with the reduction observed in MAP.


Verapamil in atrial fibrillation and atrial flutter. A double-blind randomized study was performed to compare the efficacy of intravenous verapamil with saline in 28 patients with a rapid ventricular rate and atrial fibrillation or atrial flutter. Conversion of atrial fibrillation to sinus rhythm occurred in none of 14 patients after saline and in 3 of 20 patients (15%) 7 to 160 min after verapamil. The ventricular rate in atrial fibrillation was slowed greater than or equal to 15% in 2 of 14 patients (14%) by saline, in 17 of 20 patients (85%) by 1 dose of verapamil (p less than 0.001), and in 19 of 20 patients (95%) by 1 or 2 doses of verapamil (p less than 0.001). Conversion of atrial flutter to sinus rhythm occurred in none of 4 patients after saline and in 1 of 7 patients (14%) 105 min after verapamil. The ventricular rate in atrial flutter was slowed greater than or equal to 15% in none of 4 patients by saline, in 4 of 7 patients (57%) by 1 dose of verapamil, and in 7 of 7 patients (100%) by 1 or 2 doses of verapamil (p less than 0.001).


Debrisoquin hydroxylation polymorphism among Ghanaians and Caucasians. The alicyclic and aromatic hydroxylation of debrisoquin was studied in Ghanaians. As in a previously studied Caucasian population, the alicyclic 4-hydroxylation of debrisoquin in Ghanaians was polymorphic. Three phenotypes were observed: homozygous extensive metabolizers (58%), heterozygous extensive metabolizers (36%), and homozygous poor metabolizers (6%). In contrast, British Caucasians are primarily monomorphic extensive metabolizers (92%) and homozygous poor metabolizers comprise 8% of the population. Urinary recovery of the drug and its hydroxylated metabolites was significantly less in the Ghanaian subjects. In both Ghanaian and British populations, aromatic hydroxylation producing 5-, 6-, 7-, and 8-hydroxydebrisoquin was shown to parallel the alicyclic 4-hydroxylation of debrisoquin, and thus to be controlled by the same gene locus. Debrisoquin is advocated as a tool for uncovering polymorphism in drug oxidation and its interethnic variations.


Cefamandole kinetics in uremic patients undergoing hemodialysis. A single intravenous 15 mg/kg dose of cefamandole was given to 6 patients in chronic renal failure before hemodialysis, and 3 were examined during an interdialysis period. Mean cefamandole clearance by hemodialysis was 24 +/- 12 ml/min; 35 +/- 15% of the dose was recovered in the dialysate. The cefamandole half-life (1 1/2) on dialysis was 4.0 +/- 0.29 hr; off dialysis it was 13.9 +/- 4.2 hr. High urine concentrations of cefamandole in these patients suggests usefulness in urinary tract infection.


Sulfinpyrazone kinetics after intravenous and oral administration. Sulfinpyrazone kinetics has been investigated after intravenous and oral doses. They may be described by a 3-compartment open model. In the body about half the drug is in the plasma or in interstitial fluids, which equilibrated with plasma. Most of the rest is in an extravascular compartment, from which it easily diffuses back to the plasma. About 3% of the dose is still in the body after 24 hr and is located mainly in a deep compartment. After oral administration, sulfinpyrazone is quickly absorbed, largely from the stomach.


Multiple-dose amikacin kinetics in pediatric oncology patients. Amikacin kinetics was studied in 8 pediatric oncology patients who received the drug by intravenous infusion over 30 or 60 min at a dose of 5 mg/kg every 6 or 8 hr. This regimen is recommended but, due to patient variability, patients should be monitored. Dosing intervals during 1 or 2 and 3 or 4 days of therapy were studied with serum samples collected before and at the end of the infusion and serially to the end of the dosing interval. The data appeared consistent with and were analyzed according to 1-compartment model. An equation describing serum concentration with time for the multiple-dose case was fit to each patient's multiple-interval data with nonlinear regression. Half-life averaged 1.2 hr. volume of distribution 0.24 l/kg, and total body clearance 109 ml/min/1.73 m2 or 2.51 ml/min/kg. The volume of distribution and the clearance are greater than reported for adults and probably account for the larger dose needed to achieve and maintain therapeutic levels. Although the total daily dose was greater than previously reported, there were no signs of toxicity, although therapuetic concentrations were maintained.


Effect of probenecid on cerebrospinal fluid methotrexate kinetics. The effect of probenecid (PBC) on methotrexate (MTX) kinetics in the cerebrospinal fluid (CSF) and serum was studied in 4 patients on high-dose MTX with leucovorin rescue to determine whether addition of PBC could prolong effective CSF MTX levels. Each patient received 2 courses of MTX, 1 with and 1 without PBC. PBC caused a 2.8 to 4.2-fold increase in CSF MTX concentrations but failed to prolong the CSF half-life (1 1/2). PBC prolonged the initial MTX elimination t 1/2 in the blood from 2.7 to 4.1 hr, but had little effect on subsequent t 1/2s. No effect of MTX on PBC clearance was detected. Our data suggest that in man PBC in concentrations that were high enough to inhibit the renal clearance of MTX failed to alter the clearance of MTX from the CSF when both drugs were administered systemically.


Plasma theophylline levels after sustained-release aminophylline. Healthy adult subjects were given oral sustained-release (SR) aminophylline tablets 225 mg 12-hourly (n = 12) or 450 mg 12-hourly (n = 6) for 5 doses, and all were given aminophylline 225 mg intravenously on a separate occasion to determine individual kinetic parameters. The mean plasma theophylline half-life ( 1 1/2) from the intravenous study was 5.8 hr (SD +/- 1.9). During the 12 hr after the fifth dose of SR aminophylline, the maximum and minimum mean (SD) plasma theophylline levels were 9.7 (3.2) mug/ml and 4.9 (2.0) mug/ml for the 225-mg dose, and 21.1 (2.2) mug/ml and 11.6 (4.4) mug/ml for the 450-mg dose. Side effects were generally mild in the low-dose study, but in the high-dose study 3 subjects reported headache and 1 was withdrawn after 3 doses. Two subjects also noted nausea, and 3 reported insomnia and anxiety in the high-dose study. It was concluded that there was a considerable range of doses needed to achieve adequate plasma levels, and that the formulation studied was capable of producing reasonably stable and satisfactory plasma theophylline levels once individual dose requirements had been established.


Effects of allopurinol on theophylline metabolism and clearance. The effects of allopurinol on the plasma clearance and metabolism of theophylline in man were investigated under single-dose and multiple-dosing conditions. No change in theophylline clearance was found with the concomitant use of allopurinol but 1-methylxanthine (1MX), a theophylline metabolite not previously described in man, was detected in urine during control and allopurinol treatment phases under both single- and multiple-dosing conditions. 1MX excretion increased at the expense of 1-methyluric acid (1MU) during the allopurinol treatment phase. It is proposed that the secondary biotransformation of 1MX to 1MU is mediated by xanthine oxidase.


Interindividual variation in kinetics of infused epinephrine. 1-Norepinephrine was infused continuously for 10 hr into 5 normotensive, male laboratory subjects (mean age, 32.4 +/- 1.9 yr) at a mean rate of 0.06 microgram/kg/min. Mean plasma norepinephrine (NE) rose from the preinfusion level of 0.19 +/- 0.02 microgram/l to a steady state level of 1.22 +/- 0.29 microgram/l. The mean increase in blood pressure was 21.8 +/- 0.9 mm Hg systolic and 14.1 +/- 1.0 mm Hg diastolic. The mean depression in heart rate was 12.7 +/- 1.7 beats/min. The clearance of norepinephrine ranged from 27.9 to 100.0 ml/kg/min (mean. 58.0 +/- 13.8) and was little influenced by acute hemodynamic changes. The volume of distribution ranged widely (0.09 to 0.40 l/kg), the mean value being 13.51 1. The mean norepinephrine half-life was brief, ranging from 1.45 to 2.9 min (mean, 2.09 +/- 0.34 min). There was no evidence of a slowly accumulating high-capacity low-affinity pool of norepinephrine. These results support the use of plasma norepinephrine as an index of sympathetic activity within an individual but not its validity in interindividual comparisons.


Propranolol glucuronide cumulation during long-term propranolol therapy: a proposed storage mechanism for propranolol. The comparative disposition of propranolol glucuronide (PG) and propranolol was determined in 35 patients with hypertension or coronary artery disease during initiation of propranolol therapy, during steady-state conditions, and after discontinuation of propranolol (dose range, 40 to 960 mg daily, every 6 hr). The 2.3-fold PG cumulation in plasma was identical to propranolol cumulation. PG plasma levels were about 4 times as high as propranolol levels over the whole dose range. Unexpectedly slow terminal elimination rate of propranolol (t1/2 approximately 16 to 24 hr) on discontinuation of propranolol appeared to be related to equally slow PG elimination. PG and propranolol could be detected in plasma and urine up to 3 to 5 days after propranolol discontinuation. The PG formed in man was deconjugated to propranolol in the dog after intravenous administration, suggesting that PG may serve as a storage pool for propranolol. Observations consistent with systemic and enteric deconjugation of PG, including enterohepatic recirculation, may, at least in part, explain the observed propranolol cumulation as well as the slow elimination of propranolol after its discontinuation. PG renal clearance (29 to 70 ml/min) and PG plasma levels were highly dependent on glomerular filtration rate, suggesting that PG may cumulate abnormally in patients with severe renal disease.


Rectal bioavailability of lidocaine in man: partial avoidance of "first-pass" metabolism. It is often speculated that after rectal administration drugs will enter the systemic circulation without first passing through the liver, because at least the lower hemorrhoidal veins are not connected to the portal system. To test this hypothesis, the systemic availability of the high-clearance drug lidocaine was investigated in 6 healthy subjects following administration of 200 mg intravenous, 300 mg oral, and 300 mg rectal lidocaine in a balanced crossover design. Plasma and whole blood concentrations of lidocaine were measured by capillary gas chromatography. The mean rectal systemic availability was higher than the oral: 63% vs 31% (whole blood) and 71% vs 34% (plasma). The elimination half-lifes (t1/2els) lidocaine were about the same intravenously and orally, whereas these were slightly longer after rectal administration. The oral and rectal investigations were repeated in the same panel of volunteers about 6 mo later. The mean rectal systemic availability, based on plasma concentrations, was then 67% vs 27% orally. Intraindividual variability was rather small, indicating that oral and rectal bioavailability of lidocaine is reproducible in individuals. An equation was derived for the calculation of the fraction of the dose given rectally that bypasses the liver after absorption which is slightly more than half the dose, assuming that dose is 100% absorbed. This investigation indicates that in principle it is possible to avoid, at least partly, drug loss caused by "first-pass" metabolism by giving the drug rectally.


Verapamil plasma levels and ventricular rate response in patients with atrial fibrillation and flutter. The acute effect of verapamil on the ventricular rate in atrial fibrillation and flutter was studied in 15 patients, 13 of whom had heart rate inadequately controlled with digitalis. Plasma concentrations were measured 5 and 10 min after intravenous doses of 0.075 mg/kg and 0.15 mg/kg verapamil. In 9 patients who were clinically compensated, the 0.075-mg dose alone decreased the ventricular rate to under 100/min (responders); in the remaining 6, who had acute congestive heart failure manifested by orthopnea, rales, and pulmonary congestion, ventricular rates were above 100/min after the 0.075-mg dose (nonresponders). The 6 nonresponders received the 0.15-mg dose 30 min later. In all, the response was greater when plasma drug concentration rose after the high dose, although the rate decrease was smaller than in the 9 compensated patients who received the low dose. These results can be explained by assuming an antagonism of the verapamil effect by sympathetic stimulation in nonresponders.


Plasma renin concentration and phenobarbital levels in patients with epilepsy. Plasma renin activity, renin concentration, and renin substrate were measured in patients on long-term anticonvulsant medication. An inverse correlation was observed between phenobarbital levels and renin activity or concentration. There was a positive correlation between phenobarbital and renin substrate. Since elevation of renin substrate should have resulted in increased renin activity, it is possible that phenobarbital exerts 2 effects on the renin system: induction of renin substrate synthesis and suppression of renin release.


Amantadine kinetics in healthy young subjects after long-term dosing. We investigated the disposition of amantadine in 13 healthy, young adults after long-term dosage. Doses of 25, 100, or 150 mg, randomly allocated, were taken at 12-hr intervals in syrup for 31 doses. A 1-compartment open model and complete bioavailability were assumed. Absorption rate was variable with peak concentrations in plasma occurring at 1 to 12 hr. Since the calculated area under the plasma concentration against time curve was proprotional to it, relative bioavailability was independent of dose at steady state. As the dose increased, the apparent volume of distribution decreased. Intra- and intersubject variations in trough plasma drug concentrations at steady state were less than triple for equivalent doses. Elimination of drug from plasma was consistent with a first-order process. Plasma half-lifes (t1/2s) ranged from 10.2 to 31.4 hr and were independent of dose or creatinine clearance. The ratio of renal drug clearance to creatinine clearance ranged from 1.26 to 14.97, suggesting substantial renal tubular secretion. The median ratio of plasma drug clearance to renal drug clearance approached unity.


Oral melphalan kinetics.

Oral melphalan kinetics. The systemic availability of melphalan after oral administration is not well known. Most patients are put on a fixed oral dosage regimen. We have studied the disposition of melphalan in 14 patients after single oral doses. Five were also studied after receiving the same dose intravenously. Oral melphalan had a mean plasma terminal phase half-life (t1/2) of 90 +/- 17 min. The mean area under the plasma concentration:time curve (CXT) was 53 +/- 33 micrograms . min/ml. Urinary excretion of oral melphalan averaged 10.9 +/- 4.9% during the first 24 hr. The CXT ratio (oral:intravenous) for the 5 patients studied after both oral and intravenous melphalal (0.6 mg/kg) ranged between 0.25 and 0.89 and averaged 0.56. After oral dosing in 14 fasting patients, the time at which melphalan first appeared in the plasma varied between 15 min and 6 hr. In a myeloma patient who took oral melphalan, no melphalan was found in plasma or urine up to 24 hr. Some instances of failure of tumor response to oral melphalan may be due to inadequate bioavailability rather than inherent tumor resistance.


Gestational age and indomethacin elimination in the neonate. The disposition of oral indomethacin was studied in 9 premature infants with significant patent ductus arteriosus (sPDA) with birth weights ranging from 800 to 1,960 gm and gestational ages of 28 to 36 wk. Peak plasma concentrations in most of the subjects were not observed until 3 to 4 hr after administration and ranged from 0.027 to 0.31 microgram/ml. Plasma half-life (t1/2) of indomethacin ranged from 11 to 20 hr and correlated with gestational age. Plasma protein binding studies, in samples from the premature infant using radiolabeled indomethacin, showed no difference in binding from values obtained with adult plasma (greater than 98%). Absorption of orally administered indomethacin appears to be incomplete and plasma clearance much longer than in the adult.


Changes in calcium excretion after prolonged metolazone therapy in recurrent stone formers. The handling of an acute oral calcium load in 22 men with recurrent calcium stone disease was studied before and after diuretic therapy. As a group, the patients had marginal hypercalciuria (150 mg calcium per gram of creatinine in a 24-hr urine collection). Metolazone, a diuretic with an action in the cortical thick ascending limb of Henle's loop, was given in oral daily doses of 5.0 mg for periods of 9 to 34 mo. An oral calcium load induced a rapid rise in urine calcium exeretion, which was blunted markedly by metolazone. Further analysis of the subjects revealed that one group (11 subjects) had higher baseline 24-hr calcium excretion levels and higher parathyroid hormone (PTH) than the others. The effect of metolazone in reducing the calciuric response was significant only in this group. Thus, while long-term treatment with metolazone inhibited the rise in urinary calcium excretion elicited by an oral calcium load, the effect was significant only in patients who had high baseline urinary calcium and PTH values. The reduction in calcium excretion in response to an acute calcium challenge may explain in part the beneficial effects of cortical diluting segment diuretics in recurrent stone formers.


Screening methods using sulfamethazine for determining acetylator phenotype. Analysis of sulfamethazine (SMZ) kinetics in man has revealed complexities including wide intersubject variability. In our study, an attempt was made to assess the potential influence of changes in nonmetabolic parameters (absorption and urinary elimination rate constants) on the markers of acetylation capacity normally used in clinical screening procedures to determine phenotype. Seven normal subjects were classified as slow (SA) or fast acetylators (FA) according to their metabolic rate constant for SMZ (Km), plasma SMZ half-life, and percentage of N-acetyl SMZ in a 6-hr blood sample (PI6), a 5- to 6-hr urine collection (UI5--6), or a 6-hr total urine collection (UI6). Computer simulations were applied to baseline SMZ kinetic data from these subjects, varying nonmetabolic kinetic parameters over experimentally defined ranges singly, or in parallel with 1 or more of the other parameters. The simulations indicate that all the usual phenotyping procedures were sensitive to changes in absorption and urinary elimination rate constants. While these predictions require experimental confirmation, results show that the PI6 method is least sensitive to such changes, suggesting this method may minimize errors in phenotyping screening.


A method for studying drug metabolism in populations: racial differences in amobarbital metabolism. The two main metabolites of amobarbital excreted in urine are 3'-hydroxyamobarbital (C-OH) and 1-(beta-D-glucopyranosyl) amobarbital (N-glu). When testing the metabolite ratio in small single samples of urine, it was found that the urine in a Caucasian population contained about one-third glucose conjugation and two-thirds hydroxylation product, while an Oriental population excreted both metabolites in equal proportion. Attempts to learn the causes for the different metabolite ratios led to an investigation of metabolite concentrations in urine. The sums of the average urinary concentration of C-OH was greater in Caucasians than in Orientals, no matter how the data were expressed; the reverse was true for the N-glu metabolite. C-OH data was scattered more widely among Orientals than Caucasians; this might indicate bimodality of the distribution curves. There also was a trend toward more N-glu metabolite in urine of females than of males. Measuring the metabolite/creatinine ratios narrowed the distribution range of the data, particularly after correction for sex difference in creatinine, but population differences were not changed. Expected relationships between metabolite content of urine, sampling times, and plasma half-life (t1/2) were established by calculation. A Caucasian female with no capacity for N-glucosidation was found during the first part of this population survey. An Oriental male with only trace capacity for amobarbital hydroxylation was found in the second part.


Effect of marihuana on cardiorespiratory responses to submaximal exercise. Six male chronic marihuana (MH) users exercised on a bicycle ergometer for 15 min at approximately 50% VO2max under 3 conditions: (1) not smoking (control), (2) after smoking MH containing 7.5 mg (-) delta-9-tetrahydrocannabinol, and (3) after smoking placebo marihuana (PL). The MH was administered double-blind in a counterbalanced repeated-measures design. Heart rates (HRs), arterial blood pressures (BPs), pulmonary ventilation (VE), and oxygen uptake (VO2) were measured during exercise and 15 min recovery. PL had no effect on any of the physiologic variables. Smoking MH had no effect on systolic blood pressure (SBP), diastolic blood pressure (DBP), VE, or VO2, but did induce a marked increase in heart rate which persisted throughout exercise and recovery periods, averaging 34% higher than control values at rest, 18% higher during exercise, and up to 50% higher during recovery. MH smoking increased the product of HR x SBP in all circumstances.


The nasopharyngeal soft tissue sign: a reappraisal. An increase in the thickness of the soft tissues of the posterior nasopharyngeal wall has been described in patients with a fracture of the skull base (Andrew, 1978). Measurements of this soft tissue layer made in the same way, in Southampton, have shown a striking difference in the mean and in the normal range both in adolescents and adults. The normal measurements overlap those found in patients with a fracture of the skull base and the sign is not therefore a reliable indication of the presence of such a fracture.


Pseudotumours of the oropharynx due to muscular contraction. Normal filling defects in the barium-filled oropharynx are described. These pseudotumours result from the contraction, elevation and backward pulling of the soft palate assisted by the rounded ridge (of Passavant) in the pharyngeal wall produced by contraction of the palatopharyngeal sphincter, and the action of the palatopharyngei during swallowing. Other anatomical explanations for these filling defects are mentioned. The importance of recognising the changing pattern of these defects as being normal, and their differentiation from space occupying lesions in the oropharynx is emphasised.


Acetaminophen overdose: a growing health care hazard. Clinical reports support acetylcysteine as an effective agent in the prevention of severe hepatic necrosis and mortality in acetaminophen toxicity [2, 8, 13]. The agent is safe and easily administered to the patient. Further studies are needed before acetylcysteine is considered the agent of choice in the management of acetaminophen overdosage in this country.


Peritoneal dialysis of theophylline.

Peritoneal dialysis of theophylline. The use of peritoneal dialysis as an adjunct to management of theophylline intoxication is presented. Due to the nature of the case, detailed pharmacokinetic explanation was not possible. The data indicate that appreciable quantities of theophylline can be removed using peritoneal dialysis.


A compendium of antidepressants.

A compendium of antidepressants. This compendium provides a quick reference to available tricyclic antidepressants, monoamine oxidase inhibitors, lithium carbonate, and stimulants. The charts include adult dosages, drug precautions, side effects, interactions with other drugs, and effects on clinical laboratory tests. Basic information on the prevention and management of overdose with these agents is also covered. Although the guide alone is no substitute for a thorough review, it can serve as a reminder of how these drugs are used in various clinical settings and of the problems associated with their use.


Atempted homicide with arsenic.

Atempted homicide with arsenic. An unusual method of introducing arsenic to water with homicidal intentions, where five members of the same family were poisoned, is reported. The obvious initial diagnosis of food poisoning or food allergy was reviewed when the story of noticing an unusual substance in the well was revealed. The patients recovered fully after conventional intramuscular dimercaprol.


Quantitative high-performance liquid-chromatographic method for determining disopyramide (Norpace) in serum. We report a high-performance liquid-chromatographic method for measuring disopyramide (Norpace, Searle) in serum. The drug is extracted from 0.5 ml of serum into chloroform containing the internal standard p-chlorodisopyramide, separated on a reversed-phase octadecylsilyl column at room temperature, and detected at 254 nm. The method is sensitive to 0.2 mg of disopyramide per liter, with a linear response to at least 10 mg/liter. Within-day precision (CV) for frozen serum pools is 8.3 (n = 21) and (n = 22) at mean concentrations of 2.6 and 5.9 mg/liter, respectively. Day-to-day precision (CV) is 9.4 (n = 80) and 9.3 (n = 29) at mean concentrations of 2.8 and 6.7 mg/liter, respectively. Recoveries for disopyramide in serum averaged 98% over the linear range when compared against an aqueous standard taken through the entire analytical procedure. The method is relatively specific, as evidenced by interference studies with over 85 drugs.


The detection of some basic drugs and their major metabolites using gas-liquid chromatography. A rapid method is described for the extraction and identification of a number of basis drugs and their metabolites in urine. Gas chromatography is used as the primary source of identification, and characteristic chromatograms and retention times for a number of drug metabolites are outlined.


The practice of medical toxicology.

The practice of medical toxicology. Two hundred twelve consecutive cases presenting to a medical toxicologist related to chronic occupational exposure (49%), acute occupational exposure (24%), and nonoccupational exposure (27%). Chief complaints were respiratory (36%), behavioral (28%), neuropathy (17%), and organic brain syndrome (10%). In 90% of patients, litigation was in process or under consideration. Referrals were from plaintiff attorneys (37%), from employers, insurance compounds, and defense attorneys (26%), and from physicians (24%). Outcome of assessment revealed 55% to be unrelated to toxic substances, 39% probably related, and 6% positively related.


Dose-response studies on tolerance to multiple doses of secobarbital and methaqualone in a polydrug abuse population. Patients from a polydrug abuse treatment program were titrated with either secobarbital or methaqualone, their primary drug of abuse, to a state of mild intoxication, consisting of lateral and vertical nystagmus, ataxia, slurred speech, and drownsiness. The mean dose required to produce each sign was compared to that determined in a similarly treated control group. Tolerance to secobarbital was more easily demonstrated than tolerance to methaqualone, and nystagmus was the least sensitive indicator of patient tolerance. The individual signs were also cumulated into a graded rating scale of central nervous system depression which would be related to the dose administered. Tolerence was easily demonstrated at the higher stages of toxicity for secobarbital in the overall patient population, but tolerance to methaqualone was only unequivocal in the subjects indicating a relatively high frequency of abuse. Tolerance to methaqualone occurred at the lower stages of toxicity, suggesting that there is a difference between tolerance to secobarbital and tolerance to methaqualone. There was no indication that patients who also abuse alcohol are more tolerant than their patient counterparts. The patients who also had a history of amphetamine abuse, however, were less tolerant than the nonusers of these drugs.


Delta-9-tetrahydrocannabinol levels in street samples of marijuana and hashish: correlation to user reactions. In a 6-year period, 435 alleged cannabis samples were accessioned by an urban street drug analysis program, and clinical histories were correlated with laboratory results. The most common reason for submission of a sample was suspicion of adulteration; however, such samples were usually unadulterated but had high potency as measured by delta 9-tetrahydrocannabinol concentration. Adverse reactions occurring in nonadulterated samples were not associated with high potencies. The validity of cannabis products distributed illicitly and analyzed was over 94%. Exotic varieties were more potent than less expensive cannabis. The absolute amount of delta 9-tetrahydrocannabinol ranged from 1.5 to 144.9 mg.


Colorimetric method for the quantitative determination of acetaminophen in serum. A colorimetric method for quantitatively determining acetaminophen in serum is presented. The procedure involves preparing a protein-free filtrate by the addition of trichloroacetic acid, hydrolyzing the acetaminophen in the filtrate to p-aminophenol, and subsequent reaction of p-aminophenol with phenol and NH4OH to form an indophenol blue chromogen. The absorbance at 620 nm of this chromogen follows Beer's law up to acetaminophen concentrations of greater than 50 mg/1. The recovery of acetaminophen from serum is essentially 100% when compared with appropriately prepared standards. Serum acetaminophen concentrations as low as 1 mg/1 can be detected. Seventy drugs were tested for possible interference and none was found to interfere with the method. The coefficient of variation (day-to-day) is 4%. This new quantitative method provides the necessary sensitivity to quantitate therapeutic as well as toxic serum concentrations of acetaminophen.


[Detachment of man from life].

[Detachment of man from life]. As an instrument and a weapon in the struggle for existence man has at his disposal the intellect which enables him, by means of language, to make use of conceptional thinking. But if he uses the intellect in order to manage the interactions with his equals, he unaffectedly has to observe and to manipulate the behaviour of his fellow-men as well as his own psychic processes like functions of intricate technical apparatuses, disregarding or violating the incalculable 'endothymic' part (strivings and feelings) of human being. Innate dispositions of behaviour, urges, moods, and  emotions, however, constitute real life. Suppression of vital powers by the laws of rationality makes civilized people suffer.


Dostoevsky and suicide.

Dostoevsky and suicide. Fyodor Dostoevsky has continued to grow in stature and influence among modern writers. His modernity is based, among other things, upon his psychological penetration of character and motive. Suicide received considerable attention and analysis in his novels and stories. Although dynamic psychiatry has always held Dostoevsky in high regard, practically all psychiatrists have tended to ignore Dostoevsky's valuable insights into the subject of suicide. This paper offers a total view of the author's contributions to suicidology, through a study of suicidal behavior in his fiction, journalism and in his own life experiences. Dostoevsky's writings are testimony to the continuous and brilliant interrelations between his fictional and journalistic narratives, his understanding of individual, family and group dynamics, his intellectual search for the roots of ideology, and the authentic experience and spiritual quest of his life.


[Normative behavior and the health of the individual. An example from an Islamic community]. The problems of individuality are demonstrated in the traditional Punjabi-Muslim society. The individual, as an independent social unit with its needs and reactions, does not exist. Hence the idea of health and disease in an individual is expressed only as in pars familiae. In spite of this the individual resists the oppression. This is demonstrated by the example of the female individual.


[The anthropology of guilt and guilt feelings]. Considering the sociological and historical relativeness of 'objective' guilt and the relativeness of guilt feelings in the light of 'objective guilt' the authors delve into the problem of whether there exists such a thing as 'objective guilt'. This is particularly relevant after considering recent American investigations by Kohlberg et al. on children's development. They show the importance of guilt feelings that are aroused quite independently of the moral status of a society or a supposed 'super-ego'. Such feelings are the individual's response to some sort of interactional annihilation of communication. Highly dependent and variable, because of their dispositional and situative connections, guilt feelings seem to represent an anthropological, universally existing factor acting as an individual response to the destruction of communication but not necessarily being related to any kind of 'objective' guilt.


[Understanding language and transference in Beckett's "Endgame"]. In the article a psychoanalytic and pragmalinguistic oriented interpretation of 'Endgame' by S. Beckett is offered. This method obviously demonstrates the necessity of interpreting 'Endgame' in connection with the communicational situation between author/text and reader/interpreter. The conclusion is that the meaning of 'Endgame' is not offered by the text alone, but lies in the process of irritation of reader and interpreter, induced by specific reactions (transferences and counter-transferences) on the text presented.


[Present day Marxist sociology and psychoanalysis]. The main common theme in psychoanalysis and Marxist sociology is the understanding that it is not consciousness that determines being, but being (spiritual, social) that determines consciousness. The different variations of Marxist movements today are in fact distant from Marx's theory of sociology. They have become representatives of utopian socialism, using anarchistic methods to achieve that aim. This development can only be understood as a social neurosis, with the narcistic frustation of the intellectual class as its cause, and grandiose claims, intolerance, dogmatic thinking and destructive behaviour as its symptoms. The only justified criticism of psychoanalysis from the pseudo-Marxist side is based on the imperfection and error in the analytical doctrine of superego. This should be replaced by the idea of conscious, subjective, emotional morality which clearly explains the aggression contained in social structures.


The element of the irrational at the beginning and during the course of delusion. Delusion is described from a phenomenological point of view. Based on the observation of 15 cases of delusion over a period of several years and 3 cases described by Japanese and American authors, I have concluded that delusion cannot be understood from a genetic, psychological or sociological standpoint alone. My aim was to discover symptoms which could not be explained by psychodynamic, sociological or other causes. Such symptoms may be called irrational (incomprehensible) symptoms. Their irrationality is analogous to the same symptoms which are described in their autobiographies by two great mystics about their ecstasy. We can see these symptoms in the accounts of Zen Buddhists. These symptoms represent experience of evidence, pseudohallucination, suffering in delusion, a message to do something, loss of awareness of time and space, the polarity of guilt and blessedness following each other in close succession and the feeling of shame. We will better understand delusion if we bear in mind the irrational factor.


2-Hydroxy- ethyl-methacrylate and di- and tetraethylene glycol dimethacrylate: contact sensitizers in a photoprepolymer printing plate procedure. In a platemaking procedure differing from Nyloprint and Letterflex, contact sensitizations to 2-hydroxy-ethyl-methacrylate, di- and tetraethylene glycol dimethacrylate and nicotinic acid were found. Preoperational testing of the complete mixture gave a false impression of safety. Preventive measures and enumeration of acrylic substances so far recognized as sensitizers or cross-sensitizers are discussed.


Antabuse treatment of nickel dermatitis. Chelation--a new principle in the treatment of nickel dermatitis. Eleven nickel-hypersensitive patients with chronic, dyshidrotic hand eczema aggravated by oral challenge with 0.6-2.5 mg nickel were treated with 100 mg tetraethylthiuramdisulfide (Antabuse) two to four times daily for 4-10 weeks. Nine of the patients experienced a flare of the dermatitis shortly after initiation of the treatment. During the course of treatment the dermatitis of seven patients cleared, improvement was seen in two patients, and in two the dermatitis remained unchanged. Flare was seen in six patients when the treatment was discontinued. Seven patients experienced side effects such as fatigue, headache and dizziness. The treatment of four patients was discontinued due to side effects. During the treatment high levels of nickel were found in the serum and urine.


A postal survey of patients with nickel and chromate dermatitis. A postal survey was made of 75 patients with nickel and chromate dermatitis who had been discharged from the clinic; 69% of patients replied to the questionnaire and in 81% of these the dermatitis was still active. In many patients (48%) this was causing significant disability long after initial presentation to the clinic (average of 56.5 months). All patients had patch tests performed and the relevance of this is discussed with reference to nickel dermatitis.


Evaluation and relevance of isolated test reactions to cobalt. During a 5-year period, 286 of 4,034 (7.1%) standard tested eczema patients reacted to cobalt. Fifty (1.2%) showed "isolated" cobalt reactions (i.e. without simultaneous reaction to chromium and/or nickel). A follow-up study of 36 of these patients included a serial dilution test (SDT). Eleven of 15 patients with negative reactions in the SDT had demonstrated weak reactions in the previous standard test, whereas stronger initial reactions had been noted in 19 of 21 patients who reacted positively. Sixteen SDT-positive and six SDT-negative patients were definitely or probably exposed to cobalt in their working or home environments. The majority of patients with "isolated" cobalt sensitivity also had other contact sensitivities (especially to rubber chemicals) or atopic dermatitis. Therefore in some cases of "isolated" cobalt reactions another contact sensitivity or skin disease may be a prerequisite for the development of cobalt allergy. It is however possible that the simultaneous presence of reactivities to different test substances is only a reflection of general skin vulnerability. An uncertainty in testing methodology must also be considered when evaluating test reactions to cobalt. Finally, present results show that cobalt allergy unassociated with contact sensitivity to other substances or other skin diseases is rare.


Effect on growth and nickel content of cabbage plants watered with nickel solutions. Chinese cabbage plants were watered with different concentrations of NiCl2 solutions and the effect on growth and uptake of nickel in the plants were studied. No toxic effect on plant growth was observed. A higher content of nickel was found in the plants exposed to more concentrated nickel solutions. Nickel contamination and its clinical consequences are discussed.


Epidemiological survey of occupational contact dermatitis of the hands in Belgium. A total of 400 patients suffering from hand eczema were patch tested to 25 chemicals (20 from the standard series of the ICDRG plus five from the Tri-Contact of Belgium); 197 (49.2%) had a positive patch test to one or more substances, and there was no significant difference in the prevalence between males and females. Potassium dichromate and PPD mix were statistically more frequently involved as skin allergens in males than in females, whereas nickel sulphate, thiuram mix and neomycin sulphate gave a significantly higher number of positive responses in women than in men. Results of this epidemiological survey are discussed in the light of similar studies from the literature.


Polyvinyl chloride work boots in the management of shoe dermatitis in industrial workers. A sugar refinery worker developed allergic contact dermatitis of his feet secondary to rubber accelerators in his work boots. The dermatitis resolved when polyvinyl chloride work boots were substituted. The importance of controlling hyperhidrosis in the management of foot dermatitis in workers is discussed.


Photoallergic contact dermatitis to men's perfumes. Three patients with photosensitive eruptions related to the use of different men's perfumes were evaluated. We found that they were photoallergic to musk ambrette, an inexpensive, readily available synthetic perfume ingredient. Studies of cross-reactivity with other perfumed colognes and after-shave lotions suggest that musk ambrette is present in clinically significant concentration in large numbers of other cosmetic products.


Persistence of contact allergy to chromium. Forty-eight patients with a positive patch test to potassium dichromate 0.5% were retested after 4-7 years; 38 patients (79%) still had a positive patch test. Chromate allergy seems to be persistent. In 72% of the cases a history of occupational exposure to chromates could be proved.


Speculations on the evolution of sterol structure and function. The essential oxygen requirement for sterol biosynthesis dates this molecule as a relative latecomer in cellular evolution. Structural details of the cholesterol molecule and related sterols can be rationalized in terms of optimal hydrophobic interactions between the planar sterol ring system and phospholipid acyl chains in the membrane bilayer. The prediction that the cholesterol precursor lanosterol (4,4',14 trimethyl cholastadienol) is incompetent for membrane function is verified by in vivo experiments with eucaryotic sterol auxotrophs and microviscosity measurements of sterol-containing artificial membranes. For procaryotic cells the sterol specificity is very much broader. Methylococcus capsulatus produces 4,4-dimethyl- and 4-monomethyl sterols, but not sterols of the cholesterol type. Similarly lanosterol and its partially demethylated derivatives satisfy the sterol requirement of Mycoplasma capricolum. A more primitive but unspecified role of cyclized squalene derivatives is therefore postulated for procaryotic membranes. The finding that cholesterylmethyl ether satisfies the sterol requirement of certain microbial systems is at variance with current views on the role played by the sterol hydroxyl group in membrane organization and function.


Regulation of protein synthesis.

Regulation of protein synthesis. Synthesis of globin in reticulocyte lysates depends on the presence of heme, the prosthetic group of hemoglobin. In the absence of heme, an inhibitor of polypeptide chain initiation is activated. The inhibitor is a cyclic AMP-independent protein kinase that catalyzes the phosphorylation by ATP of the small subunit of the initiation factor eIF-2. This blocks the interaction of eIF-2 with eIF-2-stimulating protein (ESP) that is essential for initiation. Our observations are consistent with the view that the inhibitor is activated by phosphorylation catalyzed by a cyclic AMP-dependent protein kinase. Heme inhibits this enzyme and, in this way, prevents activation of the inhibitor of chain initiation.


Spirit possession and spirit mediumship from the perspective of Tulu oral traditions. The phenomenon of spirit possession is looked at in relationship to the broad cultural context in which it is found to exist in a region of southern India. The author critically reviews various attempts to explain spirit possession as solely a psychological or sociological event. Instead, he turns to the region's spirit possession and mediumship cults, oral traditions and social ideology for an ethnographically relevant interpretation of spirit possession.


Self-care in rural areas of India and Nepal. Self-care during illness and pregnancies by individuals and their families is a ubiquitous and integral part of societies throughout the world. This paper reports findings about self-care practices identified during four studies carried out over a ten-year period involving about 14,000 interviews in 7,400 households comprising over 48,000 people in three Indian states and three districts of Nepal. The proportion of ill individuals using self-care over a two-week period in the different study areas ranged from 19 to 42 percent. This involved 5 to 9 percent of the total population in self-care activities during these two weeks. Much larger differences were found between India and Nepal in the use of self-care during pregnancies. Self-care or care by relatives and friends was the predominant source of maternity care in Nepal, including deliveries, while Indian maternal care was dominated by traditional birth attendants. Comparisons also were made between self-care and the use of professional healers or health care services during the same time period. Differences in the use of self-care by age, sex, caste, access to government or special project services, type of illness, and duration and severity of illness have also been shown. The need for similar, better standardized surveys in combination with intensive studies examining the details and rationale behind self-care practices in different societies has been stressed as an essential step in developing programs to expand or modify self-care practices of individuals and their families.


Potential and effective meaning in therapeutic ritual. Anthropologists who accept the functionalist dogma that everything in a culture is related to everything else can easily demonstrate from their own point of view that any ritual is richly meaningful. If, then, the healing power of therapeutic ritual depends on making illness meaningful, any ritual, if seen from this perspective, should be efficacious. We must distinguish, however, between potential and effective meaning, i.e. what a ritual might mean and what it does mean to participants in it who generally lack an anthropologist's global view of their culture. Effective meaning can be assessed by examining a ritual's relevance to the situation in which it occurs and factors which facilitate or hinder communication of what it might mean to particular persons. This argument is illustrated by analyzing the meaning of a Chinese healing ritual in two different situations in which it occurs.


Lexemic change and semantic shift in disease names. The lexicon of illness terms used by Mexican American women is affected by the practice of speaking both Spanish and English and by the coexistence of several health systems. When there is changning participation in various health systems, with increasing interference and code switching, linguistic evidence for these changes may be found. In some cases an English disease name is borrowed. In others, a cognate is coined from an English disease name. Some terms, now no longer useful, are dropped. Finally, some Spanish disease names which do not have equivalents in English or in scientific medical theory may be retained, but there is a shift in the meaning of the words themselves. The direction of the shift is towards semantic correspondence with the concepts of scientific medicine. In these ways the medical lexicon is changed, with the changes reflecting a new medical culture.


Anthropology and mental health: reflections on interdisciplinary growth. The publication of Joseph Westermeyer, ed., Anthropology and Mental Health: Setting a New Course, is the departure point for taking stock of past and present links between anthropology and psychiatry. These reflections relate historical trends to the conference volume which contains examples of recent interdisciplinary research. The article critically reviews some of these and then suggests other recent or current work, not mentioned, which the author considers representative of some of the promising results of anthropological contributions to psychiatric interests. Questions are raised, but left unanswered, which might be further examined in attempts to continue long established interdisciplinary collaboration.


Sociocultural stress and the American native in Alaska: an analysis of changing patterns of psychiatric illness and alcohol abuse among Alaska natives. This paper presents selected morbidity and mortality statistics to outline developing trends and the current status of psychiatric illness and alcohol abuse among the Aleut, Athabascan, Yupik, Inupiat, Tlingit, Haida and Tsimpshian people of Alaska. Analysis of the records of the Indian Health Service, the Community Mental Health Centers and the Alaska Psychiatric Institute, the providers of care for Alaska Natives, shows that the number of individuals treated as inpatients and outpatients for psychiatric illness and alcohol abuse has been rising steadily. Accidental injury and suicidal behavior are common. The treated prevalence rates for these diagnoses exceed recorded rates for other American Native and non-Native groups. For each category of violent death, suicide, homicide, accidents and alcohol, rates for Alaska Natives are higher than rates for Alaska non-Natives, American Indians and the U.S. (all races) and are rising. The data suggest a public health problem in which the primary elements are behavioral disturbance and violent death.


Variations regarding susto causality among the Cakchiquel of Guatemala. George Foster's model of 'personalistic' and 'naturalistic' disease theories is employed in the present analysis of fright-sickness among Cakchiquel villagers in highland Guatemala. Field data from Panajachel and San Antonio Aguas Calientes suggest that pronounced intrasocietal competition favors personalistic interpretation, with sorcery cited as the ultimate source, rather than naturalistic interpretation, which emphasizes chance or destiny. Village differences in subsistence echology and internal competition apparently underlie variations in both the social function and assumed etiology of fright-sickness.


Elementary systems of medicine.

Elementary systems of medicine. The beliefs about causes of disease, orientations to medical problems, and the treatment practices of relatively small and elementary societies are reviewed and analyzed. Selected published reports of this problem area of ethnomedicine serve as source material. An attempt is made to induce generalizations which will serve as a possible baseline for studies dealing with related material pertaining to more advanced societies.


Enhanced responses to aerosolized bronchodilator therapy in asthma using respiratory maneuvers. To determine if respiratory maneuvers may enhance the response to inhaled bronchodilator drugs, we evaluated the bronchodilator responses when isoproterenol was: inhaled as a bolus high (80 percent VC) compared to low (20 percent VC) lung volumes, and inhaled as a single 800 microgram dose compared to four 200 microgram doses given 20 min apart. Nine asthmatic subjects inhaled isoproterenol sequentially at high and low lung volumes on two separate days; 15 others inhaled single doses of 200, 400, 600, and 800 microgram isoproterenol on four separate days. FEV1, specific conductance (Gaw/VL), Vmax50%, and the slope of phase 3 of the single-breath nitrogen test (deltaN2/L) were measured 10 min after each dose. FEV1 and Gaw/VL increased and deltaN2/L decreased more following inhalation at high compared to low lung volume (P less than 0.05). Gaw/VL increased more in the group given 800 microgram in divided doses than the group given a single dose (P less than 0.05). These findings suggest that the bronchodilator response to isoproterenol may be enhanced by inhaling the drug in divided doses sequentially and by delivering the drug near maximal inspiration. An enhanced response after the latter maneuver may be due to more uniform distribution of the drug to airway receptor sites.


Diagnostic value of bronchial aspirate and postbronchoscopic sputum in fiberoptic bronchoscopy. The contribution of the bronchial aspirate and postbronchoscopic sputum toward the establishment of a correct diagnosis of bronchogenic carcinoma was evaluated. A total of 273 patients underwent diagnostic bronchoscopic procedures during a 27-month period. One hundred four of these 273 patients were eventually found to have bronchogenic carcinoma. The combination of biopsies by forceps and brushings yielded the diagnosis in 61 (97 percent) of 63 endoscopically visible tumors. Neither bronchial aspirates nor postbronchoscopic specimens of sputum produced an additional diagnosis. The same combination yielded a diagnosis in 17 (41 percent) of 41 endoscopically nonvisible tumors. In these endoscopically nonvisible tumors, unlike tumors, a combination of bronchial aspirates and postbronchoscopic specimens of sputum produced a total of eight additional diagnosis. Thus, the overall diagnosis of endoscopically nonvisible tumors was improved from 41 percent (17/41) to 61 percent (25/41). Both bronchial aspirates and postbronchoscopic specimens of sputum were therefore important sources of diagnosis in endoscopically nonvisible tumors.


Transtracheal aspiration. Guidelines for safety. A four-year experience with transtracheal aspiration was reviewed in order to determine those patients at risk for developing life-threatening complications. One hundred procedures were performed by at least 20 different physicians trained according to an established protocol. Complications were limited to minimal subcutaneous emphysema in 19 percent (10/52), pneumomediastinum in 3 percent (3/93), and gross but self-limited hemoptysis in 1 percent (one patient); occasional unifocal premature ventricular contractions were noted in one patient. We conclude that patients not at risk of developing life-threatening complications from transtracheal aspiration can be identified. They (1) are able to cooperate and have a clearly identifiable and normal cricothyroid membrane, (2) have the procedure performed only by well-trained or supervised physicians, (3) have an arterial oxygen pressure of at least 70 mm Hg with administration of supplemental oxygen, and (4) have a prothrombin activity of at least 65 percent of the control value or a normal bleeding time or a platelet count of at least 100,000/cu mm. To minimize subcutaneous emphysema or pneumomediastinum, no patient should have therapy with intermittent positive-pressure breathing or any other procedure that might induce coughing for the subsequent 24 hours.


Hemodynamics and echocardiograms before and after cardioversion of atrial fibrillation to normal sinus rhythm. Hemodynamic and echocardiographic measurements were obtained in 15 patients prior to cardioversion and immediately, one, three, and five hours after cardioversion of atrial fibrillation to normal sinus rhythm. At five hours after cardioversion, there was improvement in cardiac index (P less than 0.005), in stroke index (P less than 0.005), and in stroke work index (P less than 0.025), but no significant change in heart rate, mean pulmonary capillary wedge pressure, left atrial dimemsions (LAD), left ventricular end-diastolic dimensions (LVEDD), or left ventricular end-systolic dimension (LVESD). At follow-up one week to nine months after cardioversion, 10 of the 15 patients (67 percent) remained in normal sinus rhythm. Neither the size of the left atrium, changes in hemodynamics, LAD, LVEDD, or LVESD, nor the presence or amplitude of the A-wave on the mitral valve echogram correlated with the persistence or normal sinus rhythm.


Breathlessness and mouth occlusion pressure in patients with chronic obstruction of the airways. In order to evaluate the hypothesis that the sensation of dyspnea is due to an "inappropriate relationship between length and tension" in the respiratory musculature, studies were performed in 24 patients with chronic obstruction of the airways. They were divided into two groups solely on the basis of subjective and objective presence or absence of breathlessness and dyspnea at rest. Spirometric tests and body plethysmography were performed in each patient. The ventilatory pattern at rest was recorded and repeated measurements of mouth occlusion pressure were made. It is concluded that breathlessness in patients with airways obstruction is not associated with major differences in arterial blood gases or in VO2, VE, f or the pattern of individual breaths; there is a greater degree of airway obstruction and increased inspiratory neuromuscular drive. The minute ventilation achieved for a given inspiratory neuromuscular output, which may be considered analogous to the length-tension relationship of the respiratory musculature, is significantly decreased. These results are in accordance with the theory of mechanical inappropriateness as a cause of dyspnea.


Safety and effectiveness of terbutaline in children with chronic asthma. The bronchodilator and cardiovascular effects of orally administered tablets containing 2.5 mg of terbutaline and 25 mg of ephedrine were compared in a double-blind parallel manner in children (ages, 7 to 14 years) weighing 25 to 50 kg (44 to 110 lb). Both drugs produced bronchodilation within one-half hour, and this effect was maintained up to six hours, with a peak between two and three hours. Small increases in the pulse rate were measured within an hour following administration of both drugs. No significant variation was noted in blood pressure. No adverse effects (including tachyphylaxis and tremor) were observed for either drug during a three-month period. Both bronchodilator agents were shown to be equally effective in the dosages used. Terbutaline is a safe bronchodilator drug when administered orally in 2.5-mg doses for children with chronic asthma in this range of ages and weights, with minimal cardiovascular side effects and effective bronchodilation.


Nocturnal pulmonary hypertension in patients with chronic obstructive pulmonary disease. Oxygen desaturation occurs during sleep in some patients with COPD. To investigate the effects of these hypoxemic episodes on the pulmonary vasculature, we studied four patients with our routine polysomnographic techniques and simultaneously recorded pulmonary artery pressure. In all four subjects, nocturnal episodes of desaturation were accompanied by elevations in the pulmonary artery pressure. Low flow oxygen abolished the drops in arterial oxygen saturation (but not the breathing abnormalities) and no elevations in the PA pressure were observed. We postulate that in some COPD patients these initially transient events may lead to sustained pulmonary hypertension and cor pulmonale. Nocturnal oxygen therapy may be indicated in more patients than previously suspected and may prevent the development of cor pulmonale.


Pulmonary hemorrhage and edema due to inhalation of resins containing tri-mellitic anhydride. Seven young men developed acute pulmonary hemorrhage and edema from the inhalation of powder or fumes of a bisphenol epoxy resin containing tri-mellitic anhydride (TMA) while working in a steel pipe-coating plant. The illness was characterized by cough, hemoptysis, dyspnea, fever, weakness and nausea or vomiting. Chest roentgenograms showed either a bilateral or unilateral pulmonary infiltrate. All patients had a normochromic type of anemia. Pulmonary function studies demonstrated a restrictive defect, hypoxemia, and increased A-a DO2 gradients. Light and electron microscopic studies of lung tissue revealed extensive bleeding into alveoli but no basement membrane deposits were seen and no antiglomerular basement membrane antibodies were detected. The patients improved quickly without treatment. Follow-up studies of six patients three weeks to one year after their illness revealed apparent recovery. A detailed medical survey carried out on all 29 workers currently employed in the plant revealed five additional men had experienced severe recurrent pulmonary problems.


Myocardial contractility in patients with ischemic heart disease during long-term administration of quinidine and procainamide. Direct measurement of segmental shortening with radiopaque epicardial markers. The purpose of this investigation was to determine whether long-term oral administration of commonly prescribed doses of quinidine sulfate and procainamide hydrochloride to patients with ischemic heart disease affects myocardial contractility. Segmental contractility, assessed by the systolic shortening fraction, the relative change in interclip distance from diastole to systole, was measured by cineradiography of metal clips that had been sutured to the epicardium at the time of coronary artery bypass surgery. Global contractility was assessed by gated blood-pool scintigraphy. Systolic shortening fraction determinations and scintigraphy were obtained following five to seven days' administration of procainamide (500 mg every four hours), quinidine (200 mg every six hours), or neither drug in a random sequence. Serum drug levels (milligrams per liter) were 1.8 +/- 0.8 (mean +/- 1 SD) for quinidine and 3.7 +/- 1.1 for procainamide, when measured one hour before the next dose. During quinidine administration, mean segment shortening fraction decreased only slightly, but significantly (P less than 0.02), from 12.4 percent to 10.6 percent. The clinical importance of so small a change is questionable. During procainamide administration, there was a very small, insignificant (P greater than 0.9), decrease in segmental shortening. Global left ventricular function was not significantly changed by either drug. It appears that both drugs can be used over long periods in commonly prescribed doses in patients with ischemic heart disease without a major overall deleterious effect on cardiac performance.


Radiographic features of Legionnaires' disease. Serial chest radiographs of 35 patients with confirmed Legionnaires' disease were evaluated. A unilateral, unilobar alveolar infiltrate was, in general, the initial radiographic finding. Progression to consolidation or to new areas of involvement was typical. Every lobe was involved, but lower lobe involvement was most common. Pleural effusion was often present. Cavitation was not seen. Radiographic progression for several days following institution of therapy, and despite clinical response, was noted. In patients who survived, radiographic improvement of abnormalities was usually apparent within two weeks of therapy. Aradiographic spectrum exists and, although many features are typical, no single feature is pathognomonic.


Symptomatic coccidioidomycosis following a severe natural dust storm. An outbreak at the Naval Air Station, Lemoore, Calif. Eighteen newly diagnosed cases of symptomatic cocidioidomycosis developed two to four weeks following exposure to a severe natural dust storm. The population at risk consisted of 26,000 residents of the San Joaquin Valley with access to health care at the Naval Hospital, Lemoore, Calif. Eight patients were white, and ten were nonwhite. The number of cases per 100,000 was estimated to be 36 for the white group and 254 for the nonwhite group. The disease was disseminated in four patients, and all were from the nonwhite group. One patient with disseminated disease, a black man, died. These data suggest that nonwhites may be relatively more susceptible to acquiring primary disease, in addition to developing disseminated disease. Dust storms of this magnitude must be considered a threat to health for populations living within areas endemic for coccidioidomycosis.


Hemodynamic improvement following a single dose of oral phentolamine. Administration in patients with chronic low output cardiac failure. Hemodynamic studies were made in 15 patients with chronic low output cardiac failure before and following a single dose of oral phentolamine (150 mg). After two hours significant (P less than .05) reduction occurred in mean pulmonary, wedge and right atrial pressures and increases in cardiac index and heart rate. In ten patients studied at four hours, wedge pressure remained significantly reduced (-18 percent) and cardiac index significantly increased (+19 percent) from control values. Oral phentolamine results in significant hemodynamic improvement in patients with severe heart failure. Duration of effect for at least four hours after a single dose suggests that intermittent oral therapy may be useful in the management of such patients.