Ectrodactyly, ectodermal dysplasia and cleft palate (EEC syndrome). Report of a family and review of the literature. A family is described in which a father and son are affected with ectrodactyly, ectodermal dysplasia and cleft palate. This particular constellation of major malformations may constitute a variant form of the EEC syndrome which characteristically includes cleft lip with or without cleft palate. From a review of the cases previously reported in the literature, autosomal dominant inheritance is the most likely mode of transmission of these conditions.


Further evidence for the existence of genetically determined metabolic differences between Lp(a+) and Lp(a-) individuals. Thirty, presumably healthy, middle-aged males from Northern Sweden were studied in September 1973 and again in February 1975. Mean fasting cholesterol and triglyceride concentrations were significantly higher at the latter investigation than they were at the former in the total group and in the Lp(a+) group, but not among those who were Lp(a-). Furthermore, estimation of free thyroxine factor yielded significantly higher results in the Lp(a-) than in the Lp(a+) group. In a previous paper, we reported significant differences between Lp(a+) and Lp(a-) individuals with respect to the relationships between insulin level and blood glucose concentration, and between insulin level and fasting triglyceride concentration. The combined results of the present and previous studies suggest that inherited metabolic differences exist between Lp(a+) and Lp(a-) individuals. In view of the association which has been found between the phenotype Lp(a+) and coronary heart disease it seems plausible that these differences may be of clinical importance.


45,XO/46,XYg dic mosaicism in a patient with ambiguous genitalia. 45,XO/46,XYq dic mosaicism was found in a patient with ambiguous genitalia. The patient had dysgenetic testis and gonadoblastoma. The same mosaicism was found in skin and gonadal tissue cultured fibroblasts. Localization of the genes related to height and male determination is discussed.


The X chromosome in Duchenne's muscular dystrophy. A search for deficiencies on one X chromosome of four obligatory and four probable heterozygotes for Duchenne's muscular dystrophy was unsuccessful. This probably excludes deficiencies larger than half the width of any band or interband.


Chromosome survey of new patients admitted to the four maximum security hospitals in the United Kingdom. In a survey of male patients admitted to the four maximum security hospitals in the United Kingdom during 1972 and 1973, 26 out of 611 (4.26%) karyotyped were found to have chromosome abnormalities. Of these, 13 (2.13%) had a 47,XYY abnormality; 5 (0.8%) were chromatin positive but two of these had cell lines that included an extra Y chromosome, one being a 48XXYY male and the other a mosaic 48,XXYY/XYY. Eight patients with autosomal abnormalities included two with Down's syndrome and a 47,XY,+21 karyotype, two with small supernumerary chromosomes, 47,XY+mar, and two with inherited balanced translocation. As in the prevalence studies of patients in these high secruity hospitals, the significant finding was the very high frequency of males with extra Y chromosomes. In this survey, it was most marked in the younger patients and particularly in those who were aged 20 years or less (approximately 6%). As a group the XYY males were therefore significantly younger than all other male admissions. As in previous surveys thay were also significantly taller and 60% were 185 cm or more in height. There were no other distinguishing physical characteristics associated with the 47,XYY karytype. In all but two patients the behaviour disturbances were attributable to psychopathic disorders and mental subnormality was diagnosed no more frequently than in the total population studied (approximately 50%).


Three successive prenatal diagnoses of 47,XY,+21. Within 3 working days in September, 1974, we made three prenatal diagnoses of 47,XY,+21 from three women of advanced maternal age. Two were 37 and 38 years old, respectively, and nulliparous. One was 42 years old and had four normal children. The possibility of cell contamination arose when the second diagnosis of trisomy 21 and a male fetus was made. This suspicion increased when the third case was found within 3 working days. All three cases were then studied with both Q and G banding for identification of individual chromosome markers. Fortunately, the distinction was clear by Q-banding. Each case showed characteristic Q-banding polymorphisms in No. 3 and No. 21 chromosomes. It was evident that these were three separate cases. Problems relating to diagnosis of two or more successive identical trisomies of the same sex can be resolved by banding techniques. The response each family had to learning the diagnosis is presented and discussed.


Partial trisomy 5 with a carrier parent t(5p-;9p+). The significance of partial trisomies of the B group is as yet unknown. An infant with multiple congenital anomalies was found to have a partial trisomy 5p+ syndrome. The father of this patient demonstrated a 5/9 translocation carrier state. A discussion of the relationship of the partial 5p+ syndrome to the Cri du chat syndrome is noted. Partial trisomy 5 would not appear, as yet, to represent a clearly definable syndrome.


Experimental cutaneous leishmaniasis. V. Protective immunity in subclinical and self-healing infection in the mouse. This study shows how infection of CBA mice with L. tropica can be manipulated so as to mimic the principal features of both subclinical and self-healing cutaneous leishmaniasis in man. CBA mice were infected with graded inocula of L. tropica promastigotes. The pattern of primary infection was found to be dependent on dose of infecting organisms: mice given low dose inocula (10(2), 10(3)) developed subclinical infections; those given high dose inocula (10(4), 10(5), 10(6)) developed overt, clinical lesions. Size and duration of lesions, and antibody production were directly proportional to dose; delayed hypersensitivity responses were inversely proportional to dose. Protective immunity to challenge infection was induced by both subclinical and clinical infection; and was manifest both during and after the healing stages of primary lesions. Protective immunity was also induced by artificial immunization with sonicated promastigotes in adjuvants but was only manifest if the challenge dose was not too large. The course of challenge infections differed depending on the method of immunization, i.e. whether by infection or artificial immunization. Lymphoid cells from immune CBA mice conferred protection on recipient syngeneic CBA mice against challenge infection; serum from immune mice did not, but suspension of immune peritoneal cells in immune serum enhanced their protective capacity. The experimental induction of protective immunity by low-dose infection, without a clinical allergic response at the site of inoculation, is of importance in designing an immunoprophylactic approach to human leishmaniasis.


Effects of acetylsalicylic acid on normal human peripheral blood lymphocytes. Inhibition of mitogen- and antigen-stimulated incorporation of tritiated thymidine. Since mechanisms for known anti-inflammatory effects of acetylsalicylic acid (ASA) in rheumatic or immunological diseases are poorly understood, we have studied effects of ASA on in vitro responses of human lymphocytes. Viable lymphocytes from normal individuals were cultured sterilely at 10(6) cells/ml in RPMI 1640 supplemented with 20% pooled AB plasma, at 37degreesC, 5% CO2. Replicate cultures were incubated with or without adding ASA and unstimulated or stimulated by PHA, Con-A, PWN, Candida, or SK-SD. Cultures contained greater than 95% mononuclear and greater 80% viable cells before pulsing with [3H]TdR, harvesting, and counting. Results indicated that adding 3-40 mg/100 ml ASA to culture resulted in significant inhibition of mitogen-induced blastogenesis. As little as 5-10 mg/100 ml ASA caused approximately 30% inhibition of [3H]TdR uptake, and virtually complete inhibition occurred with 20 mg/100 ml of ASA. Stimulation of cells from persons who were skin-test positive for Candida and SK-SD by these antigens in vitro was similarly suppressed by ASA. Exposure of cells to ASA before stimulation in medium without ASA still demonstrated time- and concentration-dependent inhibition of blastogenesis. Cells from normal individuals, obtained immediately and several days after orally ingesting therapeutic amounts of ASA (plasma level 23 mg/100 ml), cultured in medium without ASA, stimulated less well to mitogens that did cells obtained from these persons before ASA ingestion. These data show that: (i) therapeutic concentrations of ASA inhibit lymphocyte blastogenesis to both mitogens and antigens; (ii) inhibition was non-cytotoxic and partially reversible; and (iii) cells from normal subjects who had ingested therapeutic amounts of ASA responded less well to mitogens in vitro than before ASA ingestion. These observations are pertinent to clinical investigations of cellular immune response of individuals on drug therapy and to the possible mechanism(s) of anti-inflammatory action of ASA in immunologically mediated diseases.


In vitro synthesis of immunoglobulins, secretory component, complement and lysozyme by human gastrointestinal tissues. II. Pathological tissues. An in vitro culture technique has been used to study synthesis of proteins by biopsies of human gastrointestinal mucosa which were obtained at endoscopy or surgery from patients with biliary gastritis, atrophic gastritis, peptic ulcer, gastric cancer, coeliac disease, Crohn's disease and ulcerative colitis. As in normal mucosa, immunoglobulin synthesis was found in all sites, but marked increases, especially in IgG, were seen in biliary gastritis and ulcerative colitis. In untreated coeliac disease, synthesis of IgG and IgM was increased. Synthesis of complement components did not differ from that found in normal mucosa. Increased lysozyme synthesis was seen in Crohn's disease. This study shows that useful information may be acquired from short-term culture studies of the small biopsies obtained with fibre optic endoscopes.


Binding of thyroid microsomes by lymphocytes from patients with thyroid disease and normal subjects. Lymphocytes that could bind 125I-labelled thyroid microsomal membranes (ABL) were present in the peripheral blood of patients with various types of thyroid disease as well as in normal healthy subjects. In patients with anti-thyroid cytoplasmic antibodies the number of ABL was about three times normal (11-21 +/- 0-60 compared with 3-26 +/- 0-18 per 10(4) lymphocytes). In contrast, in patients with thyroid disease without anti-thyroid cytoplasmic antibodies, the number of antigen-binding lymphocytes was not significantly greater than in the normal controls (3-94 +/- 0.14 per 10(4) lymphocytes). The binding of thyroid microsomes by antigen-binding lymphocytes could be blocked by thyroid microsomes but not by thyroid mitochondrial membranes, thyroglobulin or liver microsomes.


Autoimmunity and viral infection in diabetes mellitus. Forty-three newly diagnosed insulin-dependent diabetics and thirty control subjects have been examined for cellular hypersensitivity to different pancreatic preparations, rat liver mitochondria and Coxsackie B4 virus. Evidence for cellular hypersensitivity to the pancreatic preparations was shown in the diabetic group, in whom the hypersensitivity to the pancreatic preparations was found to correlate with hypersensitivity to rat liver mitochondria. Hypersensitivity to Coxsackie B4 virus was not found to differ significantly in the diabetic and control groups. Hypersensitivity to liver mitochondria appeared to decrease over a 1-year period. There was an indication that hypersensitivity to Coxsackie B4 was greatest 3 months after diagnosis.


IgM levels and IgM-mediated immune responses in patients with acute hepatitis A, acute hepatitis B and chronic HB antigenaemia. Immunoglobulin M (IgM) levels and their relationship to isohaemagglutinins, febrile agglutinins, sheep cell agglutinins, and rheumatoid factor were measured in patients with acute hepatitis A, acute hepatitis B, chronic hepatitis B antigenaemia, and normal control populations. Significant IgM elevations were observed in both types of acute hepatitis, but not in chronic hepatitis B antigenaemia. There was no correlation of the IgM level with either the prevalence or titre of any IgM-mediated immune response studied. These data suggest that the IgM elevations in both types of hepatitis may reflect virus-specific IgM synthesis.


Intracellular immunoglobulin production in vitro by lymphocytes from patients with hypogammaglobulinaemia and their effect on normal lymphocytes. The ability of peripheral blood lymphocytes from twenty-two patients with late onset (acquired or common variable) hypogammaglobulinaemia to produce immunoglobulin was assessed by the immunofluorescent detection of intracytoplasmic immunoglobulin (Ic-Ig) in cultures stimulated with pokeweed mitogen (PWM). Intracellular immunoglobulin was found in 4-9-26% of cultured cells from eighteen out of nineteen controls. In contrast nineteen out of twenty-two patients with hypogammaglobulinaemia showed values less than 1% and in ten no Ic-Ig was detected. Two of the remaining three patients showed normal values. Lymphocytes from eleven patients showing less than 1% positive cells were selected for mixture experiments. Lymphocytes from five of the eleven patients strongly depressed immunoglobulin synthesis by normal lymphocytes when mixed together in the presence of PWM. However, lymphocytes from these individual patients did not depress immunoglobulin production in all normal controls.


In vitro synthesis of immunoglobulins, secretory component, complement and lysozyme by human gastrointestinal tissues. I. Normal tissues. An in vitro culture technique has been used to demonstrate synthesis of proteins by human gastrointestinal tissues cultured in vitro. Histologically normal tissues were obtained endoscopically and surgically. IgA and secretory component (SC) were produced in all sites, but the relative intensity of IgA synthesis and SC synthesis varied. In stomach and small intestine the intensity of IgA synthesis was greater than that of SC, but in large bowel mucosa, there appeared to be an excess of SC synthesis. Synthesis of IgG and IgM was also found in all sites. Complement proteins were produced by some of the intestinal biopsies, and by parotid gland. Lysozyme was synthesized by parotid gland and by gastric mucosa, and to a lesser extent in small intestine, and rarely in large intestine. The results suggest that in addition to the local mucosal IgA system the local production of other immunoglobulins, as well as non-immunoglobulin humoral defence factors, may be important host defences of the normal gastrointestinal tract.


Characteristics of the effector cells mediating cytotoxicity against antibody-coated target cells. III. Ultrastructural studies. On the basis of electron microscopic observations, four types of cells apparently cytotoxic for antibody-coated chicken erythrocytes were identified in non-immune mouse spleen; monocytes, polymorphonuclear leucocytes, immature granulocytes and a type of lymphoid cell. Both phagocytosis and extracellular lysis of target cells were observed. Monocytes and polymorphonuclears were able to interact with the target cell by both mechanisms while the intermediary granulocytes and lymphoid cells were only capable of extracellular lysis. It is argued that these observations provide a morphological basis for the previous classification of antibody-dependent cytotoxic cells into myeloid and lymphoid cells (Greenberg et al., 1973b, 1975).


Ultrastructural studies of mouse leucocytes showing surface binding of peroxidase-conjugated lectins. Examination in the electron microscope of mouse spleen cells treated with conjugates of wheatgerm agglutinin and horseradish peroxidase has shown the surface of myeloid cells to be heavily stained. Resting lymphocytes were unstained but became positive after stimulation by phytohaemagglutinin or concanavalin A, suggesting a relationship between the presence of this surface component and the functional state of the cell and providing a further point of similarity between myeloid and lymphoblastoid cells. The conjugates have also been useful in tracing the fate of surface carbohydrates during phagocytosis.


Significance of urinary excretion of fibrin degradation products during treatment of glomerulonephritis. 189 patients with various types of glomerular disease were studied. Creatinine clearance, protein excretion and urinary excretion of fibrin degradation products (FDPs) were measured before and at various intervals (up to 42 months) after starting treatment with indomethacin, alone or in combination with other drugs. The following observations were made: a. Patients with a urinary FDP in excess of 2 mg/24 hours before treatment had a significantly lower creatinine clearance and a significantly higher protein excretion than patients excreting less than 2 mg FDP/24 hours, indicating that FDP excretion reflects the severity of the renal disease. b. During treatment, the incidence of high FDP excretion decreases progressively, but remains high in patients who ultimately develop renal insufficiency. c. There is no correlation between the initial value of FDP excretion and the subsequent changes in creatinine clearance and proteinuria during treatment. This implies either that the initial FDP excretion has no prognostic value or, perhaps more likely, that disease activity is modified by treatment. d. The best correlation between FDP excretion and evolution is found in proliferative glomerulonephritis. There are reason to suppose that, in this group at least, the treatment influenced the evolution of the disease.


The protein binding of diazepam and N-demethyldiazepam in patients with poor renal function. The plasma protein binding of diazepam and of its main metabolite, N-demethyldiazepam, was measured in patients with renal disease and in healthy volunteers by ultracentrifugation. The total and non-protein bound concentrations of diazepam and N-demethyldiazepam, and the concentration of unconjugated oxazepam in the plasma were determined by gas chromatography after an oral 10 mg dose of diazepam. In the volunteers 98% of diazepam and N-demethyldiazepam were bound to the plasma proteins. In patients with renal disease the corresponding values were 92% and 95%, respectively. In the patients with renal disease no correlation could be found between the percent protein binding of diazepam or N-demethyldiazepam in the plasma and the serum creatinine concentration. Considerable variations in diazepam concentrations at 1 and 24 hours and in N-demethyldiazepam concentrations at 24 hours were found in the patients with renal disease. In contrast to the volunteers, 5 patients out of 28 with renal disease had measurable amounts of unconjugated oxazepam in the plasma. The deficient ability of the plasma proteins of patients with renal disease to bind diazepam may increase its clinical effect.


Hepatorenal syndrome following hemihepatectomy. The hepatorenal syndrome following right hemiphepatectomy is reported in a previously healthy patient who sustained a shotgun wound in the abdomen. In spite of the development of severe oliguric renal insufficiency and the administration of massive amounts of volume expanders and furosemide, the urine sodium concentration remained very low, therby excluding the diagnosis of acute tubular necrosis. Although severe hyperbilirubinemia developed, the prothrombin time was only slightly abnormal and the liver doubled in size in the 2 weeks after surgery. The study of functional renal failure in patients with liver disease other than decompensated cirrhosis and with significant preservation of hepatic function may suggest that factors other than a circulating toxin participate in mediating the hepatorenal syndrome.


Chemical properties of glomerular basement membrane in congenital nephrotic syndrome. Glomerular basement membranes have been isolated from kidneys of three children presenting with a congenital nephrotic syndrome. The histology of renal tissue was characterized by an increase of the mesangial area mainly due to matrix. Immunofluorescent studies showed no positive staining. After isolation, the glomerular basement membranes contained no more cellular contaminants than normal membranes. Isolated abnormal membranes exhibited, as normal preparations, less than 1% DNA, RNA, phospholipids or glycosaminoglycans. Since the protein content of both membrane preparations was comparable, significant contamination by non-proteic material did not seem likely. Although the amino acid and carbohydrate composition of both normal and abnormal membranes was very similar, the folowing statistically significant differences were observed: diseased membranes exhibited an increased number of hydroxylysine, 3- and 4-hydroxyproline residues, and an increased content of glucosyl-galactosyl-hydroxlysine units. The data suggest that, in the congenital nephrotic syndrome, the production of disaccharide-rich glomerular basement membrane subunits is enhanced, which could interfere with the packing of the peptide chains and therefore account for the altered permeability of the membrane observed in this disease.


Classification of the skeletal dysplasias and the radiologic approach to their differentiation. This chapter presents a radiological classification of skeletal dysplasias, based upon the approved nomenclature of this group of disorders. This provides a practical approach to the problem of the radiological diagnosis of patients suffering from intrinsic diseases of the skeletal system, and should encourage universal adoption of the Paris Nomenclature of skeletal dysplasias in the future. Unclassifiable disorders eventually may be submitted to another conference of authorities in the field for the purpose of further refinement of the present classification.


Acrodysplasias peripheral dysostosis, acrodysostosis and Thiemann's disease. The acrodysplasias (peripheral dysostoses) are a heterogeneous group of disorders which are characterized primarily by shortened hands and feet. These disorders are associated with phalangeal cone shaped epiphyses of the hands. Further classification of these disorders is based on the type and distribution of the cone shaped epiphyses and on a variety of extra-skeletal anomalies. Thiemann's disease, added arbitrarily to this group, is an entirely different, possibly extinct "necrosis" of the mesophalangeal epiphysis, observed in males during or after puberty.


Achondroplastic and hypochondroplastic dwarfism. To ensure proper management, prognosis and genetic counseling among patients with chondrodystrophy a specific diagnosis is critical. Achondroplasia is the most common intrinsic bone dysplasia which results in short-limbed dwarfism. Because of its frequency, it is the most completely documented and understood of these conditions. Emphasis has been given to the various characteristics which allow an exact diagnosis to be made. Hypochondroplasia can be misdiagnosed unless attention is paid to the many differences which distinguish it as a separated disorder. Some ten other conditions must be considered in the differential diagnosis of these conditions.


Irvine ankle arthroplasty. Prosthetic design and surgical technique. A total ankle arthroplasty (IAA) design is presented for highly selected cases. The design stems from investigations on the anatomical and biomechanical characteristics of the human ankle joint. The prostheses are inserted through an anterior approach. Full weight-bearing is well tolerated within a few days. The immediate results on 20 ankles are most encouraging.


Arthrodesis in the presence of infection. Eradication of the joint infection with severe joint destruction in the presence of active infection has been accomplished in 8 patients by radical debridement, stable fixation and adequate postoperative drainage of wound. All patients were successfully treated by a one-stage primary arthrodesis and all patients went on to develop a solid fusion.


Pyarthrosis of the manubriosternal joint. This is a case report of primary osteomyelitis of the sternum, the only case of pyarthrosis of the manubriosternal joint the authors are able to find in the American literature. The diagnosis was established by tomogram and open biopsy. The treatment was thorough and specific antibiotic coverage.


Neurilemmomas of the forearm and hand.

Neurilemmomas of the forearm and hand. Neurilemmoma is the most common tumor arising from peripheral nerves. Although infrequently encountered, it must be included in the differential diagnosis of soft tissue tumors. Because of its cystic consistency, a neurilemmoma in the hand or wrist may be mistaken for a ganglion. In this series of 17 neurilemmomas, 6 were present in the forearm, and 11 were in the hand and wrist. There were 5 tumors in fingers, 1 in the thumb, 3 in the palm, and 2 in the wrist. In the forearm, 3 tumors involved the median nerve, 2 involved the ulnar nerve, and 1 arose from a small sensory branch of the radial nerve. Neurilemmomas arise from a benign proliferation of the Schwann cells and rarely disturb the function of the involved nerve. The tumors are well encapsulated and may be easily enucleated from the parent nerve. Resection of the involved nerve is seldom necessary except when small nerves are extensively involved.


Osteochondral fractures of the dome of the talus. Fractures of the talor dome are uncommon and may elude diagnosis despite routine roentgenograms of injured ankles. Tomograms are helpful in localizing this lesion. Surgical removal of the osteochondral fragment is often indicated. Medial lesions may be inaccessible except by osteotomy of the medial malleolus which is then fixed with a bone screw. Lateral fragments are approached through anterolateral or posterolateral ankle incisions. Of 9 symptomatic ankles, 6 had satisfactory results following surgery. The other 3 were treated conservatively, one improved; two did not. One additional asymptomatic ankle remained so with no treatment. In one case the talus also contained an unusual cystic lesion; in another there was tarsal coalition.


A fresh appraisal of tibial osteotomy for osteoarthritis of the knee. A retrospective study was performed on 189 arthritic knees treated by tibial osteotomy at the Nuffield Orthopaedic Centre, Oxford, England to determine the quality of the results. The objective results were deduced from a numerical system of grading of pain, function, and movement, for 132 osteoarthritic knees. No statistical difference was found between high and low tibial osteotomies. Varus and male knees fared better than valgus and female knees. The result was significant only for the male varus group. Correction of the angular deformity had a profound influence on the results for varus but not for valgus knees. A joint tilt increase usually occurred and was associated with increased subluxation and instability in valgus knees but decreased or unchanged subluxation in varus knees. This was held to be an important cause of failure to achieve good results in valgus knees, and appeared to be an irremedial fault of tibial osteotomy.


Load testing of geometric and polycentric total knee replacements. Static loading of implanted geometric and polycentric knee replacements was conducted in order to define fixation characteristics and load capabilities of the prostheses and the bone prostheses interface. Failures occurred in some specimens at load levels normally encountered across the knee joint during ambulation. Disruption of the tibial bone-cement interface and crushing of the tibial plateau were the modes of failure. There was no failure on the femoral side of the joint. The major determinants of stress failure suggested by this study were: (1) the tibial bone strength, (2) the design of the geometric and polycentric tibial component, and (3) method of component implantation.


Intra-articular rheumatoid nodule of the knee joint. A 44-year-old woman with a long-standing history of classical rheumatoid arthritis had an intra-articular rheumatoid nodule of the knee joint. The history, symptoms, and signs of this case were, however, almost identical to those cases previously reported. This entity has a classic presentation and distinct findings on examination which distinguish it from other intra-articular lesions of the knee.


Femoral neck fractures in young adults.

Femoral neck fractures in young adults. In 17 patients with femoral neck fractures who were between 15 and 40 years old the incidence of aseptic necrosis in patients followed more than 2 years was 18.7 per cent. The fracture was associated with other severe injuries in 40 per cent of the cases, probably reflecting the level of violence necessary to induce the fracture in young adults. Two of the 7 fractures treated with large-bore internal fixatives required secondary procedures to correct fracture displacement (this was not a complication with threaded devices). While the incidence of aseptic necrosis is no higher than that in other adult series, subsequent degenerative changes may supervene in many femoral neck fractures in this age group.


Prediction of thromboembolism following total hip replacement. Obesity, edema in the legs before surgery, a history of deep venous thrombosis, varicose veins, and a diagnosis of osteoarthrosis were associated with an increased risk for postoperative thromboembolism. Selective administration of anticoagulants to high risk but not to low risk patients should result in a reduction in total mortality following surgery. It is therefore suggested that when deciding whether prophylactic anticoagulants should be administered to a patient, consideration should be given to that patient's likelihood of developing fatal pulmonary embolism if the anticoagulant is not given, compared to the potential reduction in his risk for fatal pulmonary embolism and the increase in risk for fatal bleeding complications if the anticoagulant is used.


The treatment of slipped upper femoral epiphysis by fibular grafting. Fixation and early fusion of slipped upper femoral epiphysis can be achieved by the use of a fibular graft inserted through a lateral approach under X-ray control. Experience of the method in 18 hips has shown that fusion of the epiphysis had occurred in all cases by 19 weeks after operation whereas in 6 out of 13 cases treated with Moore's pins fusion was delayed beyond 6 months. The clinical and radiological results were comparable to those in cases treated with Moore's pins. There were no complications associated with the donor area. The method is suitable for the treatment of all stages of the condition with the exception of the most extreme degrees of chronic slip.


Central fractures of the acetabulum: a critical analysis and review of literature. Central fracture of the acetabulum is an uncommon traumatic lesion of the pelvis that is usually best managed by conservative measures. Adequate roentgenographic evaluation and closed manipulation followed by skeletal traction is essential to attain and maintain congruity of the weight-bearing dome with the femoral head. Reduction should be maintained with traction continued uninterrupted for three months. Open reduction and internal fixation may be warranted if the actabular dome elements are of sufficient size for reconstruction of the pelvic wall. An early exercise program will improve and, as a rule, restore the range of hip joint motion. Protected weight-bearing may safely begin approximately three to four months post-injury.


Intramedullary nailing of femoral shaft fractures. Ten years' experience. In 236 intramedullary nailings of femoral shaft fractures there was a 2 per cent deep infection rate, and a 7 per cent nonunion rate; 87 per cent had good primary healing; 42 per cent had further surgery after the initial nailing (two-thirds for removal of the nail). Statistical analysis of the data does not support the view that delayed internal fixation results in less nonunions. The 55 femurs nailed in the first 3 days had a nonunion rate of 11 per cent, as opposed to a 7 per cent postinjury rate for the entire series, a statistically significant increase in nonunions with the Vesely-Street nail. Intramedullary nailing has the following advantages over treatment with traction: shorter hospital stay; better knee motion; less angulation, and less shortening.


Leukocyte and serum alkaline phosphatase after hip arthroplasty, synovectomy of the knee and fracture. The alkaline phosphatase in leukocytes (LAP) was measured in patients who had undergone various types of total arthroplasty of the hip, in patients who had undergone synovectomy and in whom tibial fractures had been treated conservatively. The LAP-Score increased rapidly and reached a maximum within a few days and returned to original levels after 14 days both after soft tissue trauma and skeletal trauma. The size of the maximal increase appears to vary only with the severity of the trauma. LAP was not found to be correlated with the increase in alkaline phosphatase in the serum. The increase in serum alkaline phosphatase occurred much later and decreased much slower and occurred only after skeletal trauma. The increase in alkaline phosphatase in the serum appears to vary with severity of skeletal trauma. A significant difference in LAP (P less than 0.05) was found between patients operated upon with total arthroplasty with success and those with deep infection. The difference between these two groups was, however, larger (P less than 0.01) regarding ESR and CRP.


Radiogrammetry at four bone sites in normal middle-aged women. their relation to each other, to calcium metabolism and to other biological variables. In 167 women, ages 41 +/- 3.5 years, who constituted 80 per cent of nuns of this age group in the Omaha area, body dimensions and radiogrammetric indices were determined in (1) radius; (2) femoral shaft; (3) second metacarpal. Calcium, phosphorus and nitrogen balance were measured and calcium kinetics were calculated following oral and intravenous administration of two radioisotopes of calcium. The bone indices were significantly correlated to each other. The femoral diameter was correlated to all the kinetic variables, the radial to many, and the metacarpal to a few. All bone diameters were correlated to height, but only the femoral diameter to body weight. Femoral shaft diameter increased with time after the menopause, but was not correlated to age. There was no correlation between any bone variable and dietary calcium, absorbed calcium, or calcium balance. High dietary calcium was associated with lower bone resorption. There was no correlation between any bone variable and the urinary excretion of estrogens or 17 ketosteroids or 17 hydroxycorticosteroids. Although different bones of the skleton are qualitatively and quantitatively related, in survey work the femoral shaft should be included as a skeletal marker in addition to the second metacarpal. Femoral expansion occurs in women after the menopause. In normal women, dietary calcium is unrelated to skeletal indices.


Complete rotation of the leg with associated deformities in poliomyelitis. A case report. This is a report of a 24-year-old man with a heretofore unreported 180 degrees rotation deformity of the right leg on the thigh with the calf and heel in front and the patella and toes behind along with other associated deformities of both lower extremities in poliomyelitis. The right knee was flail and the popliteal pulsations could be felt anteriorly. The rotation deformity was successfully corrected by arthrodesis of the knee without any neurovascular damage. After correction of the other deformities, an erect posture was achieved by this patient.


Extremity gunshot wound and gunshot fracture in civilian practice. The civilian gunshot wound is a low velocity injury. Temporary cavitation does not occur in the low velocity wound and damage is confined to the projectile pathway. Extensive debridement is not indicated for this injury. Surgical cleansing is used to convert the open, contaminated wound to a clean, closed wound. Reparative and definitive reconstruction then follow to restore form and function with minimized patient hazard.


The lethal chondrodysplasias.

The lethal chondrodysplasias. The lethal chondrodysplasias are a complex group of diseases of which little is known. Three disorders have been well characterized; achondrogenesis, thanatophoric dwarfism, and the lethal chondrodysplasias with polydactyly. Pathological studies of epiphyseal cartilage confirm the separateness of these diseases but further work is necessary to specify the limits of variations. In achondrogenesis, relatively minor forms differ greatly from the usual description. In the chondrodysplasias with polydactyly, skeletal involvement appears to vary from one case to another. Furthermore, we must pursue the genetic studies in thanatophoric dwarfism where the exact mode of inheritance is known.


The narrow lumbar spinal canal or lumbar spinal stenosis. Narrow lumbar spinal canal or lumbar spinal stenosis is a not uncommon problem. Thirty-two patients with this disorder have been treated surgically at the Ochsner Medical Center between 1963 and 1973. The best method of diagnosis is a careful history and second is roentgenographic evidence, particularly the myelogram. The surgical treatment consists of total laminectomy and foraminotomy to insure complete decompression of the nerve roots. Eighteen patients have been followed from 14 to 44 months. Sixteen of the 18 considered their operations a success.


Growth following epiphyseal arrest. A simple method of calculation. Four straight-line equations are derived from standard charts of growth remaining at normal epiphyses. Calculations made from these easily memorized formulas are a guide to the proper age for epiphysiodesis in children with leg length discrepancy.


Traumatic amputations. A vietnam experience. Ninety-two acute combat amputations were performed in 70 casualities of the Vietnam conflict. In the 67 surviving patients with 83 stumps, primary closure was done in 24 limbs (30%) and delayed closure in 11 more. Closed cases were observed 2 weeks and no failures noted. In selected patients early suture of war amputations can be practiced with a satisfactory result.


Revascularization of the femoral head. A clinical and experimental study. Most large long-term follow-up studies of displaced femoral neck fractures treated by internal fixation show a 20-35 per cent late collapse of the femoral head. Clinical observations on factors such as age, time of collapse and isotopic evidence of bone turnover, seem to indicate that a strong revascularization potential may be more harmful than helpful. Experiments on completely devascularized femoral heads in dogs reveal that those allowed to revascularize showed creeping "osteoporosis" with partial or complete collapse in almost 50 per cent of the hips. Those canine femoral heads prevented from revascularizing showed much less osteoporosis and collapse, and the articular cartilage seemed to survive and function adequately for the 2 1/2 year duration of the experiment.


How frequent is bacterial superinfection of the pharynx in infectious mononucleosis? Observations on incidence, recognition, and management with antibiotics. Throat cultures from 133 patients with infectious mononucleosis were compared with cultures from 2,881 patients who were seen during the same period because of pharyngitis. Less than 3 per cent of the cultures from each group contained Group A beta hemolytic streptococci. The inflamed pharynx and necrotic tonsils of infectious mononucleosis are seldom subject to bacterial superinfection, either initially or during the course of the illness. There is no indication for routine use of antibiotics when infectious mononucleosis is diagnosed. Should, however, a throat culture indicate presence of a bacterial pathogen, any appropriate antibiotic except ampicillin may be used without increasing the incidence of skin rash.


The effect of fluoride supplementation on the strength of osteopenic bone. The strength of osteopenic bone from calcium deprived rats, quail and roosters was significantly reduced after fluoride supplementation. Using a device which measures torque, femurs from rats fed low calcium diets with 100 parts per million fluoride added to the water supply fractured at lower torque values than those values observed for rats fed a low calcium diet without fluoride. Fluoride administration and calcium restriction in adult roosters and young Japanese quail also resulted in a reduction in bone strength. This detrimental effect on bone strength must be considered in any therapeutic attempt to use fluoride ion to stimulate bone formation in osteopenic bone disorders.


The effect of methylmethacrylate on fracture healing. Fractures were created in the femur of dogs by dividing the midshaft with an airdriven saw. Immobilization was achieved with a four-hole compression plate. No methylmethacrylate supplementation was used in the control groups. In the three experimental groups methylmethacrylate was added to the internal fixation by placing it on the endosteal, periosteal, and both surfaces of the bone. Healing of the fractures uniformly failed to occur when methylmethacrylate was apposed to both periosteal and endosteal regions. Histologic, fluorescent, and autoradiographic studies indicated that the bone surface in contact with methylmethacrylate was necrotic and did not incorporate tetracycline or Ca-45. New bone occurred only on the surface which was not in contact with methylmethacrylate.


The epiphyseal dysplasias.

The epiphyseal dysplasias. The epiphyseal dysplasias are a group of heterogeneous disorders characterized by defective or excessive bone formation in the secondary ossification centers of the tubular bones and sometimes the vertebrae. Most of them are caused by the defective action of mutant genes. Their pathogenesis is unknown. Differentiation of the various entities in this group is essential for the proper management and genetic counseling of the patients.


Mesomelic skeletal dysplasias.

Mesomelic skeletal dysplasias. Mesomelic shortening of the extremities lends itself as a useful clinical and/or radiologic sign to characterize a group of hereditary bone dysplasias. Table 1 and Figure 4 are presented to facilitate the comparison between the many different types of mesomelic dwarfism. Differential diagnosis between these types is not difficult because of the specific bone changes and extraskeletal malformations present. As in many hereditary syndromes, however, there may be wide clinical variability within a single entity, and meticulous clinical and radiologic examination must be done to arrive at the correct diagnosis. Certain other forms of chondrodystrophies, such as achondroplasia, hypochondroplasia, pseudoachondroplasia and distrophic dwarfism, can be easily differentiated from the mesomelic dysplasias by their clinical features and skeletal radiographs. Nothing is known about the pathogenesis of the various forms of mesomelic dysplasias. There is no available specific treatment, although corrective surgery has benefited selected patients. The correct diagnosis is, however, important both for prognostication and accurate genetic counseling.


Diastrophic dwarfism.

Diastrophic dwarfism. Diastrophic dwarfism is an unusual variety of short-limb dwarfism characterized by the pathognomic triad of ear calcifications, hitch-hiker thumbs, and severe clubfoot. Other clinical features include joint contractures and subluxations, symphalagism of the fingers, kyphoscoliosis, hip dysplasia, and occasional cleft palate. Radiographic findings include flaring of the metaphyses of tubular bones and flattened epiphyses which appear late. The major orthopedic problem in diastrophic dwarfism is correction of the recalcitrant clubfoot deformity; cervical spine subluxation or kyphoscoliosis may also require intervention. This disorder is inherited as an autosomal recessive condition.


Metaphyseal and spondylometaphyseal chondrodysplasias. Diseases characterized by defective metaphyseal ossification, (metaphyseal chondrodysplasias) and defective spinal and metaphyseal ossification (spondylometaphyseal chondrodysplasias) constitute an important group of congenital intrinsic diseases of bones in which orthopedic treatment is of utmost interest. The most common types of metaphyseal chondrodysplasias (Jansen, Schmid, McKusick, and Metaphyseal Chondrodysplasia with Pancreatic Insufficiency and Neutropenia) and spondylometaphyseal chondrodysplasias (Kozlowski) have characteristic well-defined diagnostic features. The importance of proper diagnosis for practical reasons--appropriate medical and psychological treatment, professional training and genetic counseling--cannot be overemphasized. Elucidation of the pathogenesis in this group of diseases is bound to emerge from future histochemical and biochemical research.


Phenytoin: pharmacokinetics and bioavailability. The pharmacokinetics of a single 300-mg oral and intravenous and 14 daily 300-mg oral doses of phenytoin were studied in 6 healthy volunteers. The mean plasma elimination t1/2 was the same following intravenous (16.8 +/- 1.3 hr) and oral (17.1 +/- 1.5 hr) doses of phenytoin; however, following chronic oral administration, the t1/2 increased to 18.9 +/- 1.5 hr (p less than 0.05). The absolute bioavailability of an oral dosage form (Dilantin Kapseals) varied from 57.7 to 85.6% when based on the relationship between the corresponding single dose areas under the curve (AUCs). When based on the comparison of the AUC for multiple oral dosing with the single iv dose area, average bioavailability was 85.9% (71.8 to 106.3). Since the variation in the bioavailability and elimination of phenytoin does not allow accurate prediction of the steady-state plasma concentration, monitoring plasma levels may be of special importance.


Human serum and myocardium digoxin.

Human serum and myocardium digoxin. Linear correlation was demonstrated between serum digoxin and papillary muscle digoxin concentrations in patients undergoing mitral valve surgery. The mean ratio of myocardial tissue to serum digoxin concentrations was 6711. This result supports the use of serum digoxin as a guide for assessing the degree of digitalization under steady-state conditions.


Spironolactone. I. Disposition and metabolism. This study describes absorption, excretion, and metabolism of[20(-3)H]-spironolactone (SP) in 5 healthy men. After a single oral dose (200 mg + 200 muCi) of the drug given in alcoholic solution, the peak serum levels of the ethyl acetate-extractable tritium and the dethioacetylated metabolite canrenone were 763 +/- 400 ng/ml (mean +/- SD) and 415 +/- 145 ng/ml, respectively. These levels occurred within 3 hr. The serum half-life (T1/2) of the extractable materials was 37.3 +/- 6.53 hr. Canrenone levels declined in two phases. The T1/2 from 2.5 to 12 hr was 4.42 +/- 1.07 hr and from 12 to 72 hr was 16.8 +/- 2.75 hr. In the blood both SP and canrenone were confined largely in the plasma, and their protein binding exceeded 89% at concentrations of 550 and 710 ng/ml, respectively. In 5 days 31.6 +/- 5.87% of the radioactivity was excreted in the urine and 22.7 +/- 14.1% in the feces. Unchanged SP was not detected in the urine. The major urinary metabolites were canrenone (5.04 +/- 2.83% of dose), 6beta-OH-sulfoxide (5.21 +/- 0.93% of dose), and canrenoate ester glucuronide (6.2% of dose).


Spironolactone. II. Bioavailability.

Spironolactone. II. Bioavailability. The bioavailability of commercial 25-mg spironolactone tablets and a new tablet preparation containing 100 mg of the drug has been determined in 12 healthy male subjects. After a 200-mg oral dose of the drug given in a solution of polyethylene glycol-400, the peak plasma level of the dethioacetylated metabolite canrenone was 633 +/- 154 ng/ml (mean +/- SD) and was reached at 1.4 +/- 0.43 hr. This peak was higher and was achieved earlier than after either eight 25-mg tablets (480 +/- 155 ng/ml at 2.9 +/- 1.03 hr) or two 100-mg tablets (474 +/- 182 ng/ml at 3.0 +/- 1.37 hr). From the ratio of the 24-hr area under the plasma concentration-time curves, the bioavailabilities of the two tablet preparations relative to the solution were 99.6 +/- 18.2% and 92.1 +/- 22.9%, respectively. The amount of canrenone excreted in the urine by 48 hr was 4.48 +/- 1.26 mg (solution), 6.36 +/- 2.02 mg (eight 25-mg tablets), and 7.81 +/- 1.87 mg (two 100-mg tablets), representing 2% to 4% of the administered dose. It is concluded that urinary excretion of canrenone alone is not a reliable method for determining the bioavailability of spironolactone.


Spironolactone. III. Canrenone--maximum and minimum steady-state plasma levels. Steady-state plasma levels of canrenone have been examined in 23 healthy men who received repeated doses of spironolactone for 15 days. The dose regimens were 200 mg once a day and 50 mg 4 times a day. With both treatments the steady-state levels were reached after 3 to 4 days. With once-a-day treatment, the maximum and minimum steady-state levels were about 500 and 100 ng/ml, respectively. The minimum levels with treatment 4 times a day were about 200 ng/ml. The post steady-state half-life of canrenone with once-a-day treatment (19.2 +/- 6.57 hr) was longer (p less than 0.01) than the half-life obtained in the 4 times-a-day treatment (12.5 +/- 3.39 hr). The former half-life was similar to the log-linear phase half-life of canrenone in the single-dose studies.


Lead intoxication: effects on cytochrome P-450-mediated hepatic oxidations. Acute administration of lead to rats caused significant decreases in cytochrome P=450, ethylmorphine N-demethylase, and aniline hydroxylase activities and prolonged hexobarbital-induced sleeping times. However, chronic administration of lead to weanling rats caused no significant changes in hepatic cytochrome P-450 levels or in the microsomal oxidative enzymes over a 12-wk period. Eight patients exposed to lead in the process of burning through lead-painted steel structures for at least 3 mo showed marked effects of chronic lead intoxication on the erythropoietic system: inhibition of erythrocyte delta-aminolevulinic acid dehydratase, increased erythrocyte protoporphyrin levels, and increased urinary excretion of delta-aminolevulinic acid. Chelation therapy greatly alleviated the inhibitory effects on dehydratase activity and decreased urinary delta-aminolevulinic acid excretion. The plasma elimination rate of antipyrine, a drug primarily metabolized by hepatic microsomal enzymes, was determined in the 8 subjects prior to and following chelation therapy. In 7 of 8 subjects, chelation therapy shortened the antipyrine half-lives, but the effect was minimal. These studies show that chronic lead exposure results in significant hematopoietic inhibition of the heme biosynthetic pathway without causing significant changes in hepatic cytochrome P-450-associated enzymic activities.


N-Acetylprocainamide levels in patients with end-stage renal failure. Serum concentrations of procainamide (PA) and N-acetylprocainamide (NAPA) were measured by fluorometry in subjects with normal renal function (n = 4) and in patients with end-stage renal failure (n = 3) after administration of 6.5 mg/kg of PA-HCl orally. Two subjects with normal renal function were rapid isonicotinic acid hydrazide (INH) acetylators and two were slow acetylators. The rapid acetylators had higher peak serum levels of NAPA (1.80 mug/ml) than the slow acetylators (0.40 mug/ml). Peak serum levels of PA were essentially identical in both. The half-life (T1/2) of PA was shorter, 2.5 hr, in the rapid acetylators than in the slow, 4.1 hr. The slope of the terminal portion of the blood time curve for NAPA was steeper (-0.087) for slow acetylators than for rapid (-0.078). These apparent differences between rapid and slow acetylators are not conclusive in themselves but tend to support the differences in acetylation previously reported. In the absence of renal function, the serum levels of PA were higher and the T1/2 prolonged. The serum levels of NAPA rose slowly and reached peak levels of 2 to 3 mug/ml and declined only with hemodialysis. In 3 patients measurable levels of NAPA were still present 78 hr (0.62 mug/ml), 94 hr (0.36 mug/ml), and 124 hr (0.70 mug/ml) after the single oral dose of PA. Clearance of NAPA during clinical hemodialysis was 48 +/- 10 cc/min compared to 75 +/- 12 ml/min for PA.


Blood ethanol concentrations during and following constant-rate intravenous infusion of alcohol. Blood ethanol concentrations were determined in 7 subjects during and subsequent to a 2-hr constant-rate intravenous infusion of ethyl alcohol (8% v/v). Eight to 10 capillary blood samples were collected during the infusion and 10 to 21 samples were obtained after the infusion ceased. Thus, the total time course of blood ethanol concentrations in man was defined, both during and postinfusion. Blood ethanol concentration data from each of 6 subjects were fitted simultaneously to the two equations for the one-compartment open model with zero order input and Michaelis-Menten elimination kinetics. The average Vm[0.232 mg/(ml x hr)] and Km[0.0821 mg/ml] obtained fron these fittings correspond very closely with corresponding values estimated by the fitting of all the mean concentration-time data obtained following oral administration of 4 different doses of ethanol to 8 other fasting subjects in another study. A disproportionate increase in area under the concentration-time curve with increase in dose (gm/kg) was observed in a single subject who was infused with equal volumes of a 4% and an 8% (v/v) ethanol solution at the same constant rate.


Absorption and excretion of tolemetin in man. Tolmetin, a nonsteroidal anti-inflammatory drug, is rapidly absorbed (10 to 20 min) and rapidly excreted (T1/2 congruent to 60 min) and shows a linear dose-plasma level response in the therapeutic dose range. Tolmetin does not affect its own metabolism on chronic administration. Tolmetin is displaced, in vitro, from plasma proteins by salicylic acid. This effect is reflected in minor changes in plasma levels and pharmacokinetic parameters when aspirin and tolmetin are coadministered.


Tissue and erythrocyte distribution of digoxin in infants. The distribution of digoxin in the myocardium, skeletal muscle, erythrocytes, and plasma (or serum) was studied in 19 infants. There was a linear relationship between myocardium and serum concentrations and no saturation was observed over the serum concentration range of 0.5-8.6 ng/ml. Myocardium uptake of digoxin was nearly twice as great in infants as in adults at any given serum concentration. Erythrocyte: plasma concentration ratios of digoxin were one-third smaller during digitalization than during maintenance digoxin therapy. The latter ratios were also three times greater in infants than found previously in adults. Their findings are consistent with a greater apparent volume of distribution of digoxin in infants and may partly explain the unusually large therapeutic doses needed in infants.


Disposition of propoxyphene and propranolol in children. The disposition of propoxyphene and propranolol was studied in children by means of two protocols which minimized the number of blood samples taken from each child. Propoxyphene and its metabolite, norpropoxyphene, were measured in two plasma samples obtained from different children at various times after a single oral dose. These data were pooled and a plasma concentration/time curve was obtained which was consistent with an average T 1/2 of 3.5 hr in this population. The bioavailability of tablets and a solution of propranolol was compared with a crossover design by obtaining plasma samples at the end of the dosage interval during chronic oral administration of various doses. No clear differences in the bioavailability of the two formulations could be detected. Both drugs showed marked interindividual differences in plasma concentrations following oral administration. These findings are consistent with the high hepatic extraction ratio and large presystemic (first pass) effect previously described in adults. The large individual variability supports the concept of monitoring plasma levels as an aid to  therapy and demonstrates that the use of a weight-adjusted dose in children can be only an approximation for initial treatment.


Maternal and neonatal elimination of amobarbital after treatment of the mother with barbiturates during late pregnancy. Plasma half-lives of amobarbital were determined in newborn children of 10 mothers who had been treated with barbiturates for hypertension in pregnancy for 6 to 42 days prior to delivery. Five mothers had received amobarbital, 200 mg daily, and 5, phenobarbital, 60 to 180 mg daily. Half-lives in 7 of the babies ranged from 16.6 to 49.4 hr, comparable to those previously reported in babies of mothers who had received only a single dose of amobarbital. Thus there was no evidence of induction of amobarbital hydroxylation in these children. Two babies who had a greater than normal rise in serum bilirubin had longer half-lives (86.1 and 117.7 hr). In 1 baby whose mother had membranous glomerulonephritis, plasma amobarbital concentration did not significantly change over the period of the study.


Kinetics of carbamazepine and its 10,11-epoxide metabolite in children. The plasma steady-state concentration of carbamazepine (CBZ) and its metabolite (carbamazepine-10,11-epoxide, CBZ-epoxide) was assessed in 43 children (2-15 yr) on CBZ (Tegretol) treatment. Twenty of the children received combined treatment with other anticonvulsant drugs simultaneously. The plasma concentrations were in the same range as had been found in adult patients on corresponding doses. Only a weak correlation was noted between dose and plasma CBZ concentration in the group of children on single-drug treatment, and there was no correlation in the group of children on combined drug regimen. Plasma levels of CBZ correlated with those of the metabolite. Children on combined treatment had lower CBZ concentration and, expressed as percent of the parent drug, the metabolite concentration was significantly higher than in children treated only with CBZ. In 2 children the plasma half-life of CBZ was estimated and found to be slightly shorter than has previously been reported in adults. In evaluating the plasma level-effect relationship of CBZ, the plasma concentration of the CBZ-epoxide should be measured simultaneously because of its anticonvulsant effect and interindividual variability.


Acetaminophen elimination kinetics in neonates, children, and adults. The elimination of acetaminophen (APAP) following an oral dose of 10 mg/kg in newborn infants, children, and adults was compared. Urinary excretion of unchanged APAP, APAP-sulfate, and APAP-glucuronide was complete within 30 hr at all ages. Higher percentages of the dose were excreted in the urine as APAP-sulfate in neonates (0-2 days old) and children (3-9 yr old) than in 12-yr old children and adults. A pharmacokinetic analysis indicated that the higher rate of APAP-sulfate formation in younger age groups apparently compensated for a deficiency in glucuronide formation. No dramatic age-related differences in the overall elimination rate constant for APAP were observed despite the quantitative changes in the metabolic pathways during early childhood.


Azidomorphine: subjective effects and suppression of morphine abstinence. In man, azidomorphine, a new morphine congener, constricted pupils, produced morphine-like subjective effects and euphoria, and suppressed the morphine abstinence syndrome. Azidomorphine was 10 to 50 times as potent as morphine. It is concluded that in man azidomorphine is a typical morphine-like drug.


Pharmacokinetics of divided-dose ifosfamide. The pharmacokinetics of a divided-dose schedule of ifosfamide was investigated in 3 patients given 1, 600 to 2,400 mg/sq m/day for 3 days, with a second course of treatment 21 days later. In contrast to the biexponential decay seen with single-dose ifosfamide (5,000 mg/sq m), data for divided low-dose plasma ifosfamide are best fitted by a monoexponential decay function compatible with a one-compartment open model. Plasma half-life for ifosfamide given in the divided-dose schedule was 6.9 hr, less than half that previously reported for high single-dose ifosfamide. Renal excretion rates and clearances for unchanged drug were similar in both schedules. The proportion of drug metabolized was larger and amount of unchanged drug excreted in the urine was smaller than after single large doses. The elimination constant for unchanged ifosfamide increased from day 1 to day 2 of treatment and remained relatively stable from day 2 to day 3 in the multidose regimen, with all parameters reverting to the pretreatment values 21days later.


Effects of acetylmethadol on plasma testosterone. Plasma testosterone levels were measured in a group of 13 men maintained on acetylmethadol for treatment of opiate dependence. Prior to acetylmethadol administration, plasma testosterone levels were within normal adult ranges. Four hours following ingestion of acetylmethadol, plasma testosterone levels were significantly depressed and continued to fall 7-9 hr after drug administration. Plasma testosterone levels remained low 24-25 hr after the drug was taken, but, 48 hr following drug, plasma testosterone levels rose to values approximating those prior to drug. Depression of plasma testosterone levels following acetylmethadol ingestion was not only statistically but also biologically significant, since in many patients the levels were below the normal range for adult males.


Restorative prosthetic mammaplasty in mastectomy for carcinoma and benign lesions. It is possible to reconstruct the normal shape of the female breasts at the time of operation for carcinoma of the breast or benign lesions where the whole breast tissue is removed. This is done by the insertion of an inert silicone plastic prosthesis. This procedure avoids the mutilating effect normally associated with mastectomy. The criteria for this operation must be strictly applied if it is to be successful and if cure of the disease is not to be prejudiced. These principally involve local characteristics of the tumour and the nutrition of the skin flaps which will remain after the ablation procedure has been completed. The importance of strict adherence to the minutiae of the surgical technique is to be stressed. Failure to observe these will result in failure of the operation. It is also possible in cases with adequate skin to perform the operation as a secondary procedure where there has been an earlier mastectomy.


Breast ptosis. Definition and treatment. A definition of ptosis of the breast is given which permits differentiation of several kinds of defects to be made: pseudoptosis, partial ptosis, and true ptosis. In case of true ptosis, three degrees are described according to the nipple relation to the submammary fold and skin brassiere. An association with hypoplasia is described. The corrective techniques chosen are different according to the various types of ptosis and their possible association with various types of hypoplasia. The subpectoralis augmentation is used to insert the prosthesis in all cases.


Subcutaneous mastectomy and fibrocystic disease of the breast. There has been a considerable amount of data presented to implicate moderate to severe fibrocystic disease as a strong precursor of breast cancer. When a premenopausal woman with nodular breasts presents a biopsy examination characterized by sclerosing adenosis, intraductal hyperplasia and/or papillomatosis, microcystic disease, macrocystic disease, or lobular neoplasia, her malignant potential will be much greater than when these disease processes are absent. As a result, a prophylactic subcutaneous mastectomy is indicated and breast reconstruction with either an immediate or a delayed mammary prosthesis implantation should be performed.


The reduction mammaplasty--a combined technique. The purposes of the reduction mammaplasty are: (1) the relief of the pain and discomfort of heavy, pendulous breasts; (2) the reduction is size of the breasts to achieve a normal and pleasing result with the brassiere in place and with clothing; (3) a reasonable and pleasing contour of the breasts from front and side, without the support of clothing or brassiere; (4) normally sensitive nipples which become erect on stimulation; (5) minimal apparent permanent scarring; (6) ideally intact ducts to the nipple; (7) a breast of size allowing for examination for breast masses. It is understandable that certain circumstances may forestall the achievement of some of these objectives, such as the presence of considerable amounts of diseased breast tissue, scars from resections of lesions of the breasts or from trauma, and massive hypertrophy of the breasts which may dictate a technique requiring free transplantation of nipples and areolae. However, several of the recent techniques allow for the achievements of these goals in a large percentage of cases. A combination of the better aspects of the techniques, with minor variations, may serve to deal even better and more consistently with the problem.


The augmentation-reduction mammaplasty.

The augmentation-reduction mammaplasty. The authors have presented a technique of augmentation mammaplasty with simultaneous treatment of glandular ptosis. They recommend this double procedure-one operation surgery for those with small and ptotic breasts, where treatment by a single procedure would not suffice to give an esthetically proportioned breast. This technique is simple, should pose no circulatory problems to the involved flaps, offers a short hospital stay and a fast recovery, and avoids two separate procedures.


Pros and cons of subpectoral implantation. At the present time, there is no universally accepted surgical technique or prosthesis for augmenting breast volume. Each surgeon has to choose with regard to shape, consistency, and volume, according to his own conviction and respecting his patient's priorities. These priorities will vary with age, profession, sexual habits, and marital and social status. In order to get the best possible results, the plastic surgeon should be adept at alternative methods and should not be restricted to one technique or one prosthesis. Patients vary considerably so our methods should be diversified. Our subpectoral implantations have given us better results than our retroglandular ones, which have been performed during the same period of time and with the same prosthesis. Consequently, retropectoral implantation is still our preferred procedure. We think that this technique, with its proper indications, deserves wider application.


The tuberous breast.

The tuberous breast. The tuberous breast deformity cannot usually be corrected satisfactorily by standard augmentation mammaplasty or mastopexy. The two operative techniques described have been most helpful in dealing with this difficult problem. Anatomic differences in patients may permit or require modification of the techniques to correct a specific deformity. Although our experience to date with these techniques has been limited in number, we have been pleased with the postoperative results.


The dermal brassiere mammaplasty.

The dermal brassiere mammaplasty. With most methods, it is possible to obtain a good breast shape as an immediate postoperative result. The question is whether the satisfactory shape is permanent. The 7-year evaluation of the method described here has confirmed the safety of the procedure as well as the satisfactory conic breast shape it achieves. The result has proven to be lasting. The drooping of the gland is prevented by means of the dermopexy with firm fixation of the infra-areolar dermal pillar to the pectoral muscle. The method is indicated even for large hypertrophies as well as in cases of ptotic breasts of normal size and when combined with augmentation by silicone prosthesis for ptotic hypoplastic breasts. The careful pre-operative planning allows control of scar size with satisfactory quality since it is not exposed to undue tension. If these techniques are followed, only minor complications such as the occasional extrusion of a subcutaneous dermal stitch or, seldomly, cyst formation (as in all dermopexy methods), may occur.


The double contrast enema in ulcerative and Crohn's colitis. One hundred double contrast enema examinations using a colonic activator (veripaque in the preliminary cleansing enema and 51 conventional barium enema examinations without a preliminary veripaque enema have been performed on 94 patients with either ulcerative colitis or Crohn's disease of the colon. The severity of the disease at barium enema examinations has been graded and compared with the severity of the disease found at sigmoidoscopy. In the double contrast examination, there was agreement between the radiological and sigmoidoscopic findings in 77% of cases and a disagreement of one grade in the remaining 23% of cases. The double contrast enema demonstrated lesions in the colon proximal to the range of the sigmoidoscope of a greater severity than that seen at sigmoidoscopy in 30% of cases. It was not found possible to use the same grading method with the conventional enema, and unless frank ulceration is present, it is considered that the conventional enema is unreliable in assessing the state of the colonic mucosa. It is concluded that the double contrast enema, using a colonic activator in the preliminary cleansing enema, causes no greater risk of complications than either the conventional enema or sigmoidoscopy.


Hepatodiaphragmatic interposition of the intestine (Chilaiditi's syndrome). Hepatodiaphragmatic interposition of the intestine (HDI) is a common radiological finding in the normal population of Iran compared to Western countries (0.22% vs 0.02%). A high incidence of this finding was observed in patients with chronic lung disease (2.7%) and in women near term pregnancy (2.0%). A striking incidence of 22% was observed in patients with post-necrotic cirrhosis. Probable contributing factors are: (a) a redundant bowel with increased mobility, (b) an enlarged lower thoracic outlet in conditions such as pregnancy, emphysema, and cirrhosis with ascites, (c) an atrophic liver of post-necrotic cirrhosis, which leaves adequate space for intrusion of adjacent bowel segments. HDI of the bowel is generally an asymptomatic condition and its finding on a chest radiograph suggests atrophic cirrhosis of the liver.


The value of the fatty meal in oral cholecystography. In order to assess the value of the after fatty meal films, 232 oral cholecystograms were reviewed. Gallbladder opacification, duct visualisation, separation of gallbladder from overlying bowel gas shadows, and the demonstration of abnormalities were assessed from the pre-fatty meal films, and then again in conjunction with those taken after fat, when contraction was also assessed. Of the  200 examinations given the fatty meal, 132 were adjudged normal, 63 had gallstones, four had adenomyomatosis (one with stones), and two cholesterolosis. The post-fatty meal films, were found to be essential for the diagnosis of adenomyomatosis and cholesterolosis, and considered to be occasionally helpful in diagnosing small stones. They were of little value in assessing the biliary ducts, or separating the gallbladder from overlying bowel gas, and of no value in the diagnosis of functional biliary tract disorders.


Transient obstruction of the common bile duct following its exploration. Failure of the contrast medium to enter the duodenum during the operative cholangiography following the common bile duct exploration and instrumentation may be caused by transient obstruction of the common bile duct. It is attributed to spasm and oedema of the sphincter choledochus of Boyden and not of the sphincter of Oddi. The knowledge of the possibility of the pseudo-obstruction of the common bile duct following its exploration may save the surgeon from unnecessary re-exploration and performing sphincterotomy or choledochoduodenostomy. The exploration is unnecessary if, during the common duct exploration, the dilators and the catheter passes easily into the duodenum and on the cholangiogram the obstructed area is smooth and there is no filling defect. A normal cholangiogram performed 8-10 days following the operation proves that the obstruction was transient and not caused by calculus stricture or tumour.


On the staging of breast carcinoma.

On the staging of breast carcinoma. The implications of the new staging system for breast carcinoma proposed in 1973 by the International Union Against Cancer (UICC) in conjunction with the American Joint Committee on Cancer Staging and End Results (AJC) has been examined both in terms of staging distribution and the presentation of survival results as compared with the currently used International staging classification in a large consecutive series of patients referred for treatment between 1960-62. The new UICC/AJC system, if accepted, will require some 23% of cases at present Stage II (International) to be allocated to Stage I depending on a clinical assessment as to whether the nodes are involved or not. It will result in the reporting of increased survival rates for Stage I and Stage II disease, and this change is sufficiently large to be of statistical significance in Stage I disease at five and ten years.


Carcinoma of the male breast: report of a series of 88 cases. A series of 88 cases of male breast cancer was compared with 241 cases of female breast cancer randomly selected from Departmental records. Cases of male breast cancer differed significantly from control female cases with regard to stage of the disease, age of onset and liability to the development of a second carcinoma. In 11 of the 88 cases (12.5%) of male breast cancer another primary malignant tumour developed. In seven instances the large bowel or rectum was the site of the other carcinoma. When correction was made for age and for the stage of the disease the prognosis of breast cancer in men and women was found to be similar. Only minor histological differences were found between male and female cases. Two of 54 cases examined for X-chromatin proved to be Barr-positive.


The effects of varied numbers of dose fractions on the tolerance of normal human skin. The early and late radiation of small areas of normal human skin, included in the treatment of basal cell carcinomata, have been used to evaluate the validity of the fractions exponent of the Ellis NSD equation. Fraction numbers at the lower end of the range used clinically were investigated (3 ,7 and 10 fractions); total doses were calculated using an NSD of 1930 ret with a fractions exponent of 0.22. Time and hence the time exponent was constant (14 days). The patterns of increasing and declining early skin reaction, measured using an arbitrary numerical scoring system, and the proportion of treatment fields reaching skin tolerance were similar for the three treatment groups. The number of treated areas showing late normal tissue damage were also similar. These observations suggest that it is legitimate to apply the NSD hypothesis to treatments involving 3-10 fractions over an interval of 14 days. Of particular interest was the observation that the final cosmetic result and tumour cure was not significantly improved by treatment given as 10 fractions over that obtained with 3 fractions.


Calculation of survival rates by the life table and other methods. The last few years have seen the introduction of medical statistics into the curriculum for MB, BS and for the FFR. Also, an increasing number of clinical trials have considered statistics at the planning stage of the trial, rather than only at the end point. However, there is one particular aspect of medical statistics which has consistently been neglected, namely, technique in calculating survival rates for cancer patients. All too often, a direct method of calculation, see section 3.1, is used when a life table method would provide a better estimate. The life table, or actuarial method, was first described in a medical context by Greenwood (1926), and later by Merrell and Shulman (1955) and Cutler and Ederer (1958). It has however, not been explained in detail in a British journal. The objective of the present paper is to remedy, this fact so that it can be used more widely in the future in preference to a direct method.


Treatment of connective tissue sarcomas by local excision followed by radioactive implant. Thirty-two cases of connective tissue sarcoma were treated by local excision immediately followed by a radioactive implant, sometimes supplemented by external radiation. The method is effective in preventing local recurrence, and is particularly valuable for patients in whom persistent local recurrences following simple excision have occurred. The patient experiences little extra discomfort, and complications are unusual; hazard to staff is low. Long-term survival appears to be just as good in our series as in others in which radical surgery was used, the radical surgery has the disadvantages of greater operative morbidity and mortality, causes greater disfiguration, and may in any case be impossible for tumours in certain anatomical sites.


Whole lung tomography in metastatic disease. Because pulmonary metastases in patients with primary neoplasms have both therapeutic prognostic implications, a review was undertaken of 100 patients with primary neoplasms in whom whole lung tomography and chest roentgenography had been performed. Eight (20%) of 28 patients with solitary metastases on conventional films had more than one lesion on tomography. Due to the tomographic findings, therapy was altered in six of those eight. Two (3%) of 72 patients with normal chest roentgenograms had metastases visible on their tomograms. The data indicate the high value of whole lung tomography in determining therapy whenever a solitary metastasis is visible on conventional chest roentgenograms. The 3% pickup rate of metastases in patients with normal chest roentgenograms is less clear-cut but does suggest the contribution tomography can make in patients with potentially curable lesions.


The lymphographic pattern in Hodgkin's disease: a correlation with the Rye histological classification. Lymphograms performed before therapy in 51 patients with Hodgkin's disease have been analysed and the results related to the histology. Although a typical appearance for each histological type is described, it is not possible to predict the histological pattern from the radiographic appearances in an individual patient.


The value of radiology in the idiopathic respiratory distress syndrome: a radiological and pathological correlation study. The authors have reviewed the chest radiographs of 337 newborn babies who were referred for examination with respiratory distress. They have devised a system of grading of severity of hyaline membrane disease according to the degree of radiological changes and have been able to give a prognosis for each grade. The various complications of hyaline membrane disease have been reviewed. One hundred and sixteen autopsies were carried out and the radiological and pathological findings were correlated. A positive relationship in 82% of cases was found.


Double contrast upper gastrointestinal studies. A technique for routine hyptonic double-contrast studies of the upper gastrointestinal tract is described. It is emphasized that, to achieve consistent success, the principles of the technique must be understood and applied at the time of the examination. The various factors producing the barium coating effect are described. Gas distension and bubble control are also described. Where applicable, the principles and projections are demonstrated by examples. Endoscopy with biopsy has added a new dimension of accuracy to diagnosis and is replacing barium studies for acute upper gastrointestinal haemorrhage. Accurate barium studies are important as a screening test of other symptomatology to select patients for further clarification by endoscopy.


Double contrast barium meal examination - a comparison of techniques for introducing gas. A comparison made between five techniques for introducing additional gas to the stomach for double contrast barium examination showed effervescent tablets to be associated with significant improvement in gastric mucosal coating with significantly less bubble formation. A proprietary effervescent health salt on the other hand was associated with significantly greater bubble formation.


Post-heparin plasma lipoprotein lipase and hepatic lipase in normal subjects and in patients with hypertriglyceridaemia: correlations to sex, age and various parameters of triglyceride metabolism. 1. A selective immunochemical method was used to measure post-heparin plasma lipoprotein lipase and hepatic lipase activity in eighty-two normal subjects and in twenty patients with type IIb, IV or V hypertriglyceridaemia. In twenty-six normal subjects the activity of post-heparin plasma lipases was compared with the kinetic parameters of endogenous plasma triglyceride metabolism. 2. The activity of post-heparin lipoprotein lipase was significantly higher in normal females than in males, whereas the activity of hepatic lipase showed an opposite sex ratio. The activity of lipoprotein lipase decreased with age both in males and females, whereas no significant age variation was observed in the activity of hepatic lipase. 3. In normal subjects a highly significant negative correlation was present in both sexes between the activity of post-heparin plasma lipoprotein lipase and fasting serum triglyceride concentration, but not between the activity of post-heparin hepatic lipase and serum triglycerides. 4. The fractional removal rate of endogenous triglycerides was positively correlated to the activity of lipoprotein lipase but not to the activity of hepatic lipase. No relationship was found between the activities of post-heparin plasma lipases and the absolute turnover of serum triglycerides. 5. The mean activity of post-heparin plasma lipo-protein lipase was significantly lower in subjects with hyperprebetalipoproteinaemia than in normal individuals. However, many hypertriglyceridaemic patients had lipoprotein lipase within the normal range and there was no correlation between serum triglyceride concentration and the activity of post-heparin lipases. 6. All three patients with fasting chylomicronaemia had low post-heparin lipoprotein lipase activity. Several subjects with high post-heparin plasma hepatic lipase activity were present in the group with hyperprebetalipoproteinaemia, but the mean value of the hepatic lipase was not significantly different from normal.


The clinical measurement of skeletal blood flow. 1. A new method for measurement of skeletal blood flow is described which depends on the complete extraction of 18F in a single passage through bone. 2. Plasma concentration and urinary excretion are measured over a 2 h period. The technique of impulse analysis is used to determine the initial transfer rate of 18F to bone and extravascular extracellular fluid (ECF). The ECF component is evaluated by using a second tracer (51 Cr-EDTA or 82Br) and the bone transfer rate obtained by difference. The 51Cr-EDTA data also provide an estimate of glomerular filtration rate and enable a correction to be applied for urinary bladder retention when necessary. 3. Duplicate measurements of skeletal blood flow in eight normal male volunteers gave mean flows between 4-4 and 5-9% of blood volume/min, or about 4 ml min-1 100 g-1 of bone. The variation between normal subjects was least when the results were expressed as % of blood volume/min rather than ml/min, ml min-1 kg-1 or ml min-1 1-73 m-2 body surface area. The precision of the technique was estimated to be 16-4%. 4. Addition of 1-5% random noise to the input data resulted in an uncertainty of 8-5% in the measurement of skeletal blood flow, suggesting that improved precision depends on closer control of physiological variables. 5. In six patients with severe untreated Paget's disease of bone, skeletal blood flow was 8-4-15-3% of blood volume/min. The increase was significant in all cases. 6. The absorbed radiation dose is low, so that the measurement can be repeated.


Suppression of the renin-aldosterone system in mild essential hypertension. 1. Suppression of the renin-aldosterone system by expansion of the extracellular fluid volume with extra sodium and mineralocorticoid for 6 days was studied in nine young men with very mild essential hypertension and in ten normotensive young men. 2. Plasma renin activity, measured both supine and after 45 degrees head-up tilt, and the renal excretion of aldosterone 18-glucuronide were similar in both groups. However, after expansion of the extracellular fluid volume, hypertensive patients showed much less suppression of both variables. 3. This difference persisted despite matching for an equivalent degree of expansion of the extracellular fluid volume as indexed by the change in body weight. 4. Administration of extra sodium and mineralocorticoid produced a greater proportional fall of renal aldosterone excretion than of plasma renin activity in both groups and this dissociation was significantly more marked in the hypertensive group. 5. We suggest that (i) a relative autonomy of the renin-aldosterone system may be relevant to the pathogenesis and/or perpetuation of essential hypertension and (ii) that the syndrome of low-renin hypertension is unlikely to be associated with "mineralocorticoid" excess.


Polyuria associated with an antibody to vasopressin. 1. A patient with polyuria in whom diabetes insipidus had been diagnosed was treated with Pitressin. Resistance to this therapy developed after 18 months and a circulating antibody to vasopressin was then demonstrated. Withdrawal of therapy led to a fall in titre of the antibody and an increase in maximal urinary concentration. 2. The antibody to vasopressin was associated with the IgA fraction of the serum immunoglobulins and its characteristics are described.


The influence of sodium intake on the pressor response to angiotensin II in the unanaesthetized rat. 1. Dose-response curves for the pressor activity of angiotensin II have been determined in unanaesthetized rats receiving diets containing 2-5% (w/w) or 0-007% (w/w) sodium; the different diets were administered in various sequences. 2. In comparison with those from rats receiving a low sodium diet, the dose-response curves were displaced to the left on the high sodium diet, indicating a greater response to angiotensin, and this displacement persisted for a period of approximately 7 days after the diet was changed from high to low sodium. The dose-response curve subsequently shifted to the right when the low sodium diet was maintained for longer. 3. There was a negative correlation between the slope of the dose-response curve and the basal blood pressure in all groups; the correlation was significant in three out of the five different treatment groups. 4. Basal blood pressures were significantly raised in rats on the high sodium diet for 7 days. 5. A number of possible mechanisms have been considered to explain both the parallel shift of the dose-response curve and alteration in its slope. It is concluded that the observed findings are compatible with an action of sodium-loading on the sensitivity of the smooth muscle cell to angiotensin, on the resting of the renin-angiotensin system, on the rate of inactivation of angiotensin and on a change in initial length of the muscle fibre.


Arterial oxygenation and carbon dioxide tensions in the production of hypoxic electroencephalographic changes in man. 1. To investigate the interaction of hypoxaemia and blood PCO2 in the production of cerebral hypoxia, we studied six healthy men in whom acute progressive hypoxia was induced by using a rebreathing technique, while the PCO2 was kept constant. 2. At least two blood PCO2 tensions were studied in each subject. Arterial oxygen saturation was monitored continuously by ear oximetry, calibrated for each subject with arterialized blood. The onset of cerebral hypoxia was identified by the appearance of frontal slow waves (less than 5 Hz) in the electroencephalogram (EEG), which was recorded continuously with the bipolar 10-20 electrode placement system. 3. All subjects developed frontal slow waves during at least one experiment: the EEG changes were similar both within and among subjects, irrespective of the blood PCO2 value. 4. The arterial oxygen saturation at which slow-wave activity first occurred showed a significant inverse linear relationship to the PCO2 value at which hypoxia was induced. 5. The results imply that more profound levels of hypoxia are tolerated with high PCO2 values than with normal or low PCO2 values before hypoxic EEG changes become evident. Thus if eucapnia is maintained, EEG changes suggestive of cerebral hypoxia are unlikely to occur if arterial oxygen saturation remains above 75%.


Changes in the carotid body and the ventilatory response to hypoxia in chronically hypoxic rats. 1. Young rats were kept in a hypoxic chamber for 2-11 weeks and compared with littermate control animals. 2. The carotid bodies of the hypoxic rats enlarged, resembling those of men and animals living at high altitude. 3. Permanent blunting of the ventilatory response to hypoxia did not occur. Immediately on removal from the chamber, the rats, lightly anaesthetized, showed a smaller increase in ventilation during hypoxia than did control animals but this difference disappeared after 3 days' recovery in normoxia.


Lipoprotein lipase and hormone-sensitive lipase activities in human subcutaneous lipomas: comparison with normal subcutaneous adipose tissue. 1. Lipoprotein lipase activity and hormone-sensitive lipase activity were investigated in subcutaneous lipomas removed from two patients and compared with the enzyme activities in subcutaneous adipose tissue from two normal subjects. 2. Confirmation was obtained of the presence of lipoprotein lipase activity in lipomas with an activity fifteen to forty-five times that in the two control samples. 3. Hormone-sensitive lipase activity was demonstrated in lipomas under basal conditions of assay as well as in the presence of adrenaline plus theophylline. However, compared with the non-lipomatous fat samples, these activities were lower, as was the magnitude of the lipolytic response to adrenaline plus theophylline. 4. The significance of these measurements of enzyme activity and their role in the pathogenesis of lipomas are briefly discussed.


Fibrocartilaginous emboli as the cause of ischemic myelopathy in a dog. Acute hemiplegia and Horner's syndrome developed in a 6-year-old female black Labrador Retriever 24 hours after a day of exercise. Radiographic, cerebrospinal fluid, and electromyographic studies did not detect the site or nature of the suspected cervical lesion. The dog showed no improvement after evaluation for 5 days on corticosteroid and antibiotic therapy. Gross and microscopic examination revealed the presence of an ischemic infarct in the C6 segment of the cervical spinal cord and associated fibrocartilaginous emboli. The nature of the clinical signs and the pathologic findings in this case are similar to previous reports of human and canine cases.


The immune response of rabbits to 3 strains of Mycoplasma agalactiae var. bovis isolated from mastitic bovine udders. Rabbits were given 3 serologically-related trains of mycoplasma isolated from mastitic bovine udders. Growth inhibiting antibodies were not found. High-titered sera from each rabbit immunized with each strain developed at least 4 precipitin lines to each organism and at least one line of identity was demonstrated between the organisms. Significant indirect hemagglutination titers were found in all rabbits in 1 week, with titers reaching 1.0 X 10(5) to 3.3 X 10(5) in 4 to 6 weeks but despite continued intravenous antigenic stimulation, titers quickly fell to low levels thereafter.


Some biological and physical chemical properties of Erysipelothrix rhusiopathiae. Fourteen strains of Erysipelothrix rhusiopathiae, representing extremes of host-range and world distribution, were examined for: 1) protein composition as determined by electrophoresis and electrofocus patterns, 2) guanine-cytosine mole ratios of their respective deoxyribonucleic acids, and 3) carbohydrate fermentation patterns. No correlation is apparent between any particular physical-chemical property and virulence in mice. The role the bacterial fragments play in the pathogenesis of a rabbit model of rheumatoid arthritis is discussed.


Effectiveness of certain teat dips and sanitizers in vitro and on teat skin against Mycoplasma agalactiae subsp. bovis. Seven teat dip and sanitizer products were tested in vitro and in vivo for mycoplasmacidal activity against Mycoplasma agalactiae subsp. bovis (M. bovimastitidis). Most, but not all products tested appeared to kill the mycoplasma at satisfactory dilutions. These mycoplasma survived longer on teat skin during humid, rainy weather than during warm, dry weather. Acholeplasma laidlawii was frequently found on normal teat skin.


Normal and abnormal xylose absorption in the horse. The D-xylose absorption test was applied to clinically normal horses and to horses with signs of gastrointestinal disease. A dosage of 0.5 grams of xylose per kilogram of bodyweight was useful in detecting horses that absorbed the pentose abnormally. The clinical findings were correlated with gross and microscopic findings by biopsy and at necropsy. Gastrointestinal lesions associated with abnormal xylose absorption were classified as: 1) villous atrophy; 2) edema of the lamina propria or 3) necrosis of the lamina propria.


Reticuloendotheliosis in a dog.

Reticuloendotheliosis in a dog. A case of reticuloendotheliosis in a 7-year-old Gordon Setter is reported. Progressive weakness, debility, and diarrhea with melena were the presenting complaints. Clinical evaluation revealed splenomegaly, severe nonregenerative anemia, thrombocytopenia and leukopenia with many large blast cells in the peripheral blood. Necropsy revealed extensive involvement of bone marrow, spleen, liver, lymph nodes, kidneys, and adrenals. Gastric and duodenal ulcers were also present. The course, clinical findings and cellular characteristics of the case presented, closely resemble those reported in the syndrome of reticuloendotheliosis in cats.


Blood oxygenation and disturbances of the acid-base equilibrium in myocardial infarction. In order to trace the changes in blood oxygenation and disturbances of the acid-base equilibrium in myocardial infarction, investigations were carried out in 136 patients aged 39-83 years. The values of blood oxygenation and the acid-base status were determined on the 1st, 2nd and 3rd day of the disease, and then after one, two and three to four weeks. Besides this, in 38 patients determinations were performed 3, 6, 9 and 12 months after the onset of the disease. The determinations were careied out with a micro-Astrup unit "Radiometer". It was demonstrated that hypoxaemia is very frequent complication of myocardial infarction since it appears in about 60% of cases of uncomplicated infarction. The intensity of hypoxaemia is greatest after 2-3 days. The intensity and duration of hypoxaemia depend on the clinical course of myocardial infarction. The most intense and longest persisting hypoxaemia was seen in patients with shock and/or acute left-ventricular failure. In nearly 25% of cases hypoxaemia was present even six months after the onset of the disease. Slight metabolic acidosis was observed on the 1st day of the disease in 37% of the cases, while severe metabolic acidosis was present in patients with shock and pulmonary oedema. Compensated metabolic acidosis was found in 50-60% of the cases during one year after myocardial infarction.


Changes in circadian sodium excretion in patients with essential hypertension and with renal artery stenosis. In groups of healthy volunteers (C), patients with essential hypertension (EH), and patients with renal arterial stenosis (S), the following indicators were followed during 12-hour daytime (d) and nighttime (n) intervals: mean BP, endogenous creatinine clearance Ccr (GF), excretion of sodium (UNaV) and potassium (UKV), and their excretion fractions (CNa/GF and CK/GF). The d/n ratios of both UNaV and CNa/GF were significantly lowered in both groups of hypertensive persons as against the controls (1.5): in the EH, to 1.1, and in the S, to 0.8 on the average. Positively correlated with the value of the d/n ratio of the sodium excretion are the changes in the d/n ratios of water and solute excretions. The daytime potassium excretion exceeded the nighttime values in both groups of hypertensive persons. The d/n ratios of UKV and CK/GF were, however, significantly lowered as compared to the control values. These signs of disturbances of the circadian excretion of Na and K in EH and S exhibited no correlations with the values, or rhythms, of the mean BP, GF, or dietary uptake of sodium. The results do not indicate that the antihypertensive drugs used (alpha-methyldopa, dihydralazine, reserpine) would influence the circadian rhythm of Na excretion. The factors responsible for the disturbances of the circadian rhythms of Na and K excretion in hypertensive subjects have not yet been revealed.