The relationship between the 'idiopathic oedema syndrome' and subclinical hypothyroidism. Thyroid function has been studied in eleven patients with the 'idiopathic oedema syndrome'. Six patients have been shown to have subclinical hypothyroidism associated with the presence of thyroid antibodies. All responded to treatment with sodium thyroxine. Five patients had normal thyroid function, absence of thyroid antibodies and failed to respond to treatment with sodium thyroxine.


Hormonal regulation of the menstrual cycle in women with breast cancer: effect of adjuvant chemotherapy. The hormonal features of the menstrual cycle determined by measurement of serum LH, FSH, oestradiol, progesterone and prolactin were normal in thirteen breast cancer patients clinically disease free and not taking anti-tumour therapy. Results of similar studies during seven menstrual cycles in four patients on an adjuvant therapy programme of L-phenylalanine mustard (L-PAM) + 5-flurouracil (5-FU) also had normal hormonal characteristics after three to fourteen courses of chemotherapy. Amenorrhoea with elevated gonadotrophins occurred after seven courses of chemotherapy in one 48-year-old woman. Adjuvant chemotherapy does not appear to result in major alterations in hormone secretion during menstrual cycles of women who continue to menstruate while on therapy.


Exchange of triiodothyronine derived from thyroxine with circulating triiodothyronine as studied in the rat. At present it is widely assumed that T3 derived from T4 is rapidly and totally exchangeable within the volume of distribution of T3 secreted by the thyroid into the bloodstream. This concept is implied when conclusions are drawn from comparisons between a biological effect in a responsive tissue and circulating T3 and T4 levels. Such conclusions are often in conflict with those derived by comparing the biological effect with the concentrations of T3 and T4 in the responsive tissue itself. Thus, it appeared important to test the above assumption directly. Thyroidectomized rats have been treated for 4-4 1/2 days with a mixture of 131I labelled T4 (131T4) and 125I labelled T3 (125T3), which was either injected twice daily or administered by continuous i.v. infusion. The rats were bled, perfused, and their plasma and tissues submitted to extraction and paper chromatography. If the tested assumption were correct, the ratio between the T3 derived from T4 and the T3 injected as such (namely, the 131T3/125T3 ratio) should be the same in plasma, liver, kidney, heart, muscle, etc. It was evident that the 131T3/125T3 ratio was not the same for different tissues. The differences were not merely due to artefactual deiodinations. The presence of small amounts of 131I and 125I containing compounds in the T3 spot was considered as highly unlikely, though not totally excluded. The data thus suggest that T3 derived from T4 and the injected (or thyroidally secreted) T3 might not be totally exchangeable within an observation period which is considerably longer than the one for which complete equilibrium was previously assumed. If so, changes in the size of the T4 pool, or in the rate of T4 conversion to T3, might affect the concentration of T3 in a given tissue to an extent not disclosed from the circulating T3 levels alone. Several possible consequences of the present findings are discussed.


Experiences of patients who undergo laryngectomy. Fifty patients undergoing laryngectomy are described. The sociological and psychological consequences of the operation for the patient and his relatives are described, and the factors which govern the development of oesophageal speech.


Longterm results of ultrasonic irradiation in Meniere's disease. Thirty-seven patients with Ménière's disease were treated with ultrasonic irradiation to the lateral and superior semicircular canals. In a longterm follow-up study, lasting alleviation of the vertiginous attacks was found in 24 out of 33 patients (72%). In most of the cases, hearing remained unchanged. It is suggested that the therapeutic effect is associated with a change in the endolymphatic drainage dur to histological alterations in the labyrinth produced by ultrasound.


Unilateral grommet insertion and adenoidectomy in bilateral secretory otitis media: preliminary report of the results in 91 children. This study evaluates whether the use of grommets in the primary treatment really changes the course of secretory otitis media. The patient acts as his own control. Bilateral cases are selected and one ear is treated by a grommet, the other left intact, and all have their adenoids removed. Until now 91 children have been entered. A repeated operation was done in 13, and 6 of them had a contralateral grommet because of persisting middle ear effusion. A discharge occured from 25% of the operated ears. After the operation the intact ear showed a great improvement in the function of the Eustachian tube according to the tympanograms. The hearing level was normalized within 3 months in both intact and operated ears. In 28 children the grommets had been extruded for more than one month. By comparing the intact and the operated ears no significant statistical difference was found.


Rehabilitation of the hearing impaired adult in Denmark. An outline is given of the rehabilitation of the hearing impaired adult in Denmark. Emphasis is put on the comprehensiveness and the professionalism of the services provided.


The development of audiological services in the Cardiff area. An account of the development of audiological services in the Cardiff area is presented so that otolaryngologists may be encouraged to extend and improve the facilities present in their locality.


The mediation of the localization of polymorphonuclear leucocytes in glomeruli during the autologous phase of nephrotoxic nephritis. A passive model of the autologous phase of nephrotoxic nephritis (NTN) in rabbits was developed to study the events at the initiation of this stage of the disease. Intravenous injection of sheep anti-rabbit glomerular basement membrane antiserum was followed 48 hr later by 125I trace labelled rabbit anti-sheep IgG. Animals were killed 3 hr after the second antibody injection. Experiments were undertaken to investigate whether or not a reaction between the passive antibody Fc piece and polymorphonuclear leucocyte (PMN) Fc receptor occurred, causing the localization of PMN in glomeruli in the autologous phase of NTN. The results indicate that such a reaction is an important, but not exclusive, factor in glomerular PMN localization. The complement independence of the localization was confirmed. In addition, it appeared that PMN-dependent intraglomerular fibrin deposition was mediated exclusively by a reaction between antibody Fc piece and PMN Fc receptor.


DNA binding activity of serum from patients with systemic lupus erythematosus. The reaction conditions essential for reproducible use of the cellulose ester membrane filter assay for anti-DNA antibody levels in patients with systemic lupus erythematosus are described. A dependence of DNA-binding capacity on serum concentration was observed in the assay, requiring that serum concentrations be comparable in determinations of DNA-binding activity of different sera and when comparing different published studies. The DNA-binding capacity of serum from lupus patients was found to be significantly different from that of healthy controls. However, the binding capacities were not significantly different between lupus patients with and without nephritis. The relative avidity of the anti-DNA antibodies were estimated from plots of 1/DNA bound vs 1/DNA free and these data indicate that the avidities of the antibodies from the two groups of lupus patients are not significantly different. This observation suggests that the tightness of binding between the DNA and the serum anti-DNA antibodies cannot be used to predict immune complex-induced nephritis in lupus patients.


Effect of chronic developmental lead exposure on cell-mediated immune functions. Studies were performed to investigate the effects of chronic, low level pre- and post-natal lead exposure on cell-mediated immune function in rats. Weanling female rats were exposed to lead (as lead acetate) in their drinking water at 0, 25, and 50 ppm for 7 weeks. At the end of 7 weeks they were mated with untreated males and continued on the same dosage throughout gestation and lactation. The offspring of these females were weaned at 21 days of age and continued on the same lead exposure regimen as their mothers. These offspring were used in immune surveillance procedures between 35 and 45 days of age. Lead exposure at the levels employed had no statistically significant effect on growth and did not result in overt signs of toxicity. Thymic weights were significantly decreased in both males and females of the two lead dosage groups. Furthermore, lead exposure resulted in suppression of responsiveness of lymphocytes to mitogen stimulation and in reduced delayed hypersensitivity responsiveness. Results indicate that chronic low-level lead exposure causes suppression of cell-mediated immune function.


Tissue distribution of brain-thymus shared antigens recognized by anti-brain xenosera in the rat, dog and man. A comparative and quantitative study of the tissue distribution of brain-thymus shared antigens was carried out using rabbit antisera to rat, dog and human brain homogenates, assayed on rat, dog and human thymus cells, respectively. Quantitative absorption analyses with eleven different tissues showed that the tissue distribution of the brain-thymus antigens was strikingly different in the three species. In the rat, the antigens were present in large amounts on both brain and thymus, to a lesser extent on bone marrow cells, but not at all, or only slightly, on the other tissues studied. In the dog, the shared antigens were present in large amounts only on brain. They were present in smaller amounts (approximately 5% compared with brain) on thymus, spleen, lymph node and, unexpectedly, kidney, and to a slight extent on bone marrow cells. In both rat and dog, absorption to a plateau with liver indicated the presence of brain-thymus shared antigens of restricted tissue distribution. No brain-thymus antigens of restricted tissue distribution could be detected in man, since liver, heart, kidney, brain and all other tissue studied, excepting erythrocytes and platelets, could absorb out all the antibody.


Deficiency in kwashiorkor serum of factors required for optimal lymphocyte transformation in vitro. Blastogenic responses of normal human peripheral blood lymphocytes cultured in media supplemented with serum from children with kwashiorkor were, on average, 47.7% of those observed when the same cells were cultured in the presence of normal AB serum. Incorporation of radioactive uridine was also diminished in the presence of normal AB serum. Incorporation of radioactive uridine was also diminished in the presence of kwashiorkor serum indicating that lectin-induced RNA synthesis was also affected. The kwashiorkor serum effect was not due to a cytotoxic action nor could it be attributed to the presence of saccharides or other inhibitors of the inducing lectins. Mixing experiments showed that kwashiorkor serum was not inhibitory, but that it lacked factors present in normal serum that are required for optimal lymphocyte blastogenesis. The deficiency of these factors could largely be rectified by supplementing kwashiorkor serum with an ultrafiltrate of normal serum containing components with molecular weights of less than 500 Daltons. We conclude that nutritional deprivation of severity sufficient to cause kwashiorkor leads to a deficiency of low molecular weight lymphocyte growth factors. This lack may contribute to the immunodeficiency associated with the disease.


Inhibition of mitogen-induced human lymphocyte proliferative responses by tetracycline analogues. The effect of tetracyclines on mitogen-induced proliferative responses of human lymphocytes was examined. The results showed that of the three tetracycline analogues studied, doxycycline possessed the most potent inhibiting effects. This occurred at drug concentrations (1--10 micrograms/ml) easily attainable in serum during conventional dosage schedules. Other investigations have shown that tetracyclines also interfere with neutrophil function. Taken together, these findings may have clinical significance. Recovery from serious infections generally requires some minimal host immune responses, and the immunosuppressive side-effects of tetracyclines may have detrimental effects on patients with debilitating illnesses or impaired immunological defence mechanisms. Furthermore, tetracyclines may share some common properties of conventional immunosuppressive drugs, such as cytotoxicity, teratogenicity and cancerogenicity. The long-term use of tetracyclines for conditions such as chronic bronchitis, bronchiectasis and acne vulgaris needs to be re-examined.


ADCC against human erythrocyte target cells: role of the anti-target cell antibodies in determining lymphocyte killer activity. Studies were undertaken to investigate the role of anti-target cell antibodies in determining whether lymphocytes can mediate antibody-dependent cellular cytotoxicity (ADCC) in vitro. Trinitrophenyl (TNP) modified Chang liver cells and human erythrocytes were employed as target cells and were coated with xenogeneic and allogeneic antibodies against TNP and natural cell surface antigens. Two cytotoxic effector cell populations were used: human peripheral blood mononuclear cells (PBMC) containing both lymphocytes and monocytes, and monocyte-depleted peripheral blood lymphocytes (PBL). With Chang targets, both PBMC and PBL mediated ADCC with xenogeneic anti-Chang and xenogeneic anti-TNP sera. With human erythrocyte targets, PBMC but not PBL mediated ADCC with human anti-blood group B serum, while both PBMC and PBL mediated ADCC with xenogeneic anti-TNP sera and also with a human anti-CD serum. These results demonstrate that the source of anti-target cell antibodies employed in ADCC reactions may determine whether or not lymphocytes are capable of mediating cytotoxicity.


Anaphylactic sensitivity of guinea-pigs drinking different preparations of cows' milk and infant formulae. Guinea-pigs have been given various preparations of cows' milk or infant formulae to drink in an investigation of the capacity of these milk preparations to stimulate per os anaphylactic sensitivity. The treatment, presumably heat, used to concentrate the 'Evaporated' whole cows' milks (three brands were tested) almost abolished their sensitizing capacity to beta lactoglobulin. The brand presumed to be most heated as judged by the degree of caramelization had also lost most of its sensitizing capacity to casein. Injected parenterally, the 'Evaporated' milk adequately sensitized to anaphylaxis. An infant formula, which in its spray dried form was only moderately sensitizing to both beta lactoglobulin and casein, lost most of this sensitizing capacity when processed to a liquid concentrate state. The manufacturing process for the liquid concentrate involved greater and more prolonged heating than required for the spray-dried form. The relevance of these findings in the guinea-pig to cows' milk protein intolerance in the infant and possibly also to cot death is discussed.


Histamine 2 receptor-mediated immunomodulation in the mouse. I. Immunomodulation by the H2 agonist tolazoline. Tolazoline, a drug used in the treatment of hypertension, has been described as a typical H2 agonist. In this study possible immunomodulating properties of tolazoline were investigated. A single injection of tolazoline 1 day before immunization caused an effect on delayed hypersensitivity that depended on the antigen dose. The response to 10(5) and 10(6) sheep red blood cells (SRBC) was decreased, whereas the response to 10(9) SRBC was enhanced. Administration of tolazoline 4 days after immunization predominantly affected the humoral response. The IgM response was inhibited in favour of the IgG response. Low doses of tolazoline, given to animals simultaneously with the elicitation for delayed hypersensitivity, lead to a more severe inflammation. The possible involvement of suppressor cells and vessels in tolazoline action is discussed. The application of tolazoline in the immunotherapy of human cancer is suggested.


The in vitro evaluation of certain neutrophil and lymphocyte functions following the ingestion of 150 mg oral dose of levamisole: assessment of the extent and duration of stimulation of neutrophil chemotaxis, protein iodination and lymphocyte transformation. Certain functions of human blood neutrophils and lymphocytes were investigated at varying time intervals after the ingestion of a single 150 mg dose of levamisole. The functions tested were neutrophil chemotaxis and post-phagocytic metabolic activity and mitogen-induced DNA and protein synthesis of lymphocytes. It was found that levamisole causes a stimulation of neutrophils motility (cell- and serum-associated) and post-phagocytic hexose monophosphate shunt activity and protein iodination. Increased lymphocyte DNA synthesis, but not protein synthesis, to the mitogen phytohaemagglutinin was observed. The stimulation which was detected almost immediately of these neutrophil and lymphocyte functions was still evident 24 hr later but not at 48 hr, indicating that a single oral dose of levamisole can cause the alteration (stimulation) of leucocyte functions which persists until 24--48 hr after intake of the drug.


Phagocytic peripheral blood monocytes from rabbits and humans express membrane receptors specific for IgM molecules: evidence that incubation with neuraminidase exposes cryptic IgM (Fc) receptors. Phagocytic human and rabbit peripheral blood monocytes, identified by their ingestion of polystyrene particles, were investigated for the presence of surface membrane receptors for IgM molecules. After incubation of freshly isolated monocytes with IgM anti-sheep erythrocyte (SRBC) preparations, a mean of 0.7% of human monocytes and a mean of 16.2% of rabbit monocytes formed rosettes with SRBC. However, if the monocytes were pre-incubated with vibrio cholerae neuraminidase (VCN), these figures increased to 32.6% and 37.8% respectively. The specificity of rosette formation by VCN-treated monocytes was established in several experiments; SRBC sensitized with a F(ab')2 preparation of an IgG anti-SRBC reagent completely failed to rosette with VCN-treated monocytes, and inclusion of IgM, but not other Ig or non-Ig protein molecules in the test medium, inhibited rosette formation. Further, and most important, rosette formation by human monocytes was inhibited by F(c)5mu but not by Fabmi fragments. These findings indicate that both rabbit and human monocytes express IgM-class specific membrane receptors for IgM molecules, that these receptors may be cryptic or hidden but can be revealed by treatment with VCN and that the human monocyte IgM receptor is F(c) specific. Further, the rabbit monocyte IgM receptor was shown to be trypsin-resistant.


Plasma renin activity during the development of paracetamol (acetaminophen) induced acute renal failure in man. Plasma renin activity has been measured daily in 36 patients suffering from self poisoning with acetaminophen. In 3 developing porto-systemic encephalopathy terminal renal failure developed with high plasma renin activity. In 2 who developed acute renal failure without porto-systemic encephalopathy, plasma renin activity was noted to rise before serum creatinine and to return to initial levels after 3 or 4 days while renal failure persisted. Six other patients with similar hepatic damage showed comparable rises in renin without developing renal failure. Our findings are consistent with but do not establish a pathogenetic role for renin in acetaminophen-induced acute renal failure. It is suggested that other factors may act with renin to bring about renal failure.


Selective vitamin B12 malabsorption with proteinuria (Imerslund-Najman-Gräsbeck-syndrome): ultrastructural examinations on renal glomeruli. Renal biopsy material obtained from a 6 year old girl suffering from an Imerslund-Najman-Gräsbeck-syndrome was examined by light- and electron-microscopy. Clinically the patient presented the characteristic intrinsic factor independent vitamin B12 malabsorption with severe megaloblastic anemia and a benign nephropathy with non-selective proteinuria. Electron microscopic examination of the prenal glomeruli showed no obvious alterations of the Electron microscopic examination of the renal glomeruli showed no obvious alterations of the capillary basement membranes but revealed a considerable diffuse dilatation of the rough endoplasmic reticulum in the podocytes with accumulation of a finely fibrillar material within  the widened cisternae. This finding is interpreted as an indication that the synthesis and/or secretory activities of the podocytes, as far as the basement membrane is concerned, and thus the basement membranes themselves, may be altered with the consequence of an increased permeability of the filtration barrier. Because proteinurie contrary to anemia did not respond to parenteral vitamin B12 therapy and therefore is obviously not vitamin B12 dependent, it is assumed that both vitamin B12 malabsorption and glomerulopathy in this hereditary disease are established by a pleiotropic gene or two closely associated genes.


Nephrotic syndrome in procainamide induced lupus nephritis. We report a case of the nephrotic syndrome occurring in a patient with procainamide induced LE. It was associated with bilateral pleural effusions, pericarditis, fever, positive LE cell preparation and a high titer of antinuclear antibodies. No anti-DNA antibodies were found. Renal biopsy showed mesangial proliferation with few IgM and C3 deposits and interstitial infiltrates; electron microscopy revealed subendothelial deposits. Clinical improvement occured after steroid therapy and there was no recurrence 24 months after withdrawal of prednisone.


The effect of hemodialysis on endogenous middle molecules in uremic patients. Uremic plasma and dialysis fluid were separated by high speed gel filtration followed by gradient elution ion exchange chromatography into several UV-absorbing fractions containing middle molecules (MM) (7a, b, c, etc.), which were quantitated by integrating the peak areas of the chromatograms. Dialyzer clearance of MM was determined in vivo for two dialyzers, Gambro Optima and RP-6, but no difference could be found in spite of far better in vitro MM clearance of RP-6 than of Gambro Optima. Nor was there any difference in post-dialysis decrease in MM between the two dialyzers, or between them and two dialyzers with larger surface areas (Gambro Major and Dow HK-5). In 45 determinations of MM in blood obtained before and after dialysis, using different dialyzers, the mean decrease in MM was significantly larger than for creatinine, suggesting a much smaller distribution volume immediately available for exchange. Ultrafiltration without dialysis in 7 patients induced a significant decrease in plasma MM (7a, b, c, and g) in spite of stable osmolality, urea, creatinine, and sodium concentrations in plasma, suggesting that the reduction in body water affected the net production rate of these MM. In 5 studies, using RP-6 and a 75 l recirculating dialyzate, a rapid post-dialysis rebound was observed for MM in plasma, sometimes followed by a secondary decrease in plasma concentration. The volume of distribution of dialyzed MM, assessed from pre- and post-plasma concentrations and concentrations in the dialyzate, appeared to be much smaller than for urea and creatinine. In a stable dialysis population of 17 patients, significant negative correlations were found between pre-dialysis plasma concentrations of some MM (7a, 7b, 7f, 7g) and dialysis index or endogenous renal creatinine clearance. No such correlations were found for peaks 7c and 7d. The good correlation between 7b and dialysis index (r = 0.73) suggests that plasma determination of 7b may be used as a measure of the efficiency of MM removal.


Renin-induced massive proteinuria in man. A 30 year old man developed renovascular hypertension and extreme elevation of plasma renin activity. Daily proteinuria ranged from 13 to 31 g. There were no criteria for the diagnosis of malignant hypertension. A primary glomerulopathy was excluded by a basically normal renal biopsy from the unprotected kidney. On electron microscopy the epithelial cell foot processes were not fused, thus ruling out simultaneous lipoid nephrosis. The source of renin was removed by means of a left nephrectomy. Following the procedure the patient became normotensive, the renin values normalized and the proteinuria disappeared. The results suggest that renin can cause significant proteinuria in man.


Viscoelastic behavior of tissue in leg lengthening by distraction. The leg lengthening distraction procedure was analyzed with objectives of understanding complications which arise due to overstretching, establishing guidelines to the optimum distraction rates and the frequency of distraction, and, determining the final amount of leg lengthening. An electronic recording system was devised to provide continuous monitoring of the tractive load resulting from distraction of the leg during the elongation procedure. The mechanical behavior patterns of the involved stretched tissues domonstrate time-dependent viscoelastic effects during distraction. During a leg lenthening procedure it is desirable to establish, if possible, a regular pattern of distraction early in the process. If it is necessary in the course of treatment to reduce the distraction rate for clinical reasons, then it is preferable to keep the same number of distraction events but reduce the distraction amount. Distract at equally spaced time intervals to obtain repetitive load cycles and thereby reduce peak values of load and maintain similar stress relaxation patterns for each instantaneous load increase. The total amount of lengthening depends on the characteristics of each individual leg length discrepancy and the physical properties of each distracted tissue.


Pediatric osteomyelitis: II. Arizona hinshawii osteomyelitis. Two children with sickle cell disease and kwashiorkor developed osteomyelitis caused by an Arizona hinshawii infection. Biologically, this organism is related to the Salmonella species. The infections were successfully treated by surgical drainage and chloramphenicol.


A study of radioulnar movements following fractures of the forearm in children. The range of radioulnar movements, following fractures of the forearm bones treated conservatively in 53 children under the age of 15 years, was measured by a goniometer. The most common age group was 6-10 years. All fractures united within 8 weeks and the average follow-up was 3 years. Although subjective assessment of the result was good in all cases, 52.8% had some limitation of rotational movements. The factors which limited rotation were angulatory deformity of the bones, rotational malalignment or injury to the inferior radioulnar joint. An angulatory deformity of more than 10 degrees in a child above the age of 10 years failed to remodel adequately with growth particularly if the fracture was in the proximal half of the forearm. Rotational malalignment also did not correct with growth.


Traumatic bowing of the forearm: a case report. In a 16-year-old girl, the forearm was caught between rollers in a textile factory. The tangential force caused massive swelling and one week later bowing of the forearm was noticed. One month and 3 months later the bowing was unchanged, and caused 30 degrees limitation of pronation while supination was normal. Bowing of the forearm bones in children following trauma, interperted as a plastic deformation of bone, is only recently recognized as a clinical and roentgenological entity.


Congenital vertical talus and its familial occurrence: an analysis of 36 patients. Thirty-six patients (57 feet) showing congenital vertical talus were treated at the St. Louis Unit of the Shriners Hospital between 1958 and 1978. A high incidence of congenital hip dislocatiom, arthrogryposis, congenital hypoplasia of tibia and CNA disorders was noted as associated abnormalities. These patients are classified in 3 groups: (I) primary isolated form (16 patients); (II) associated form without neurological deficit (12 patients); (III) associated form with neurological deficit (8 patients). Fifty per cent of the patients with primary isolated form had positive family history of foot deformities in their first degree relatives. Familial incidence of congenital vertical talus was observed in 2 families studied. Genetic factors may play an important role in the etiology of the primary isolated form of congenital vertical talus. The current treatment is a one-stage open reduction of the talonavicular dislocation, combined with a posterior release. A subtalar bone block is often imperative to maintain correction. Cast correction alone has never succeeded as the definitive treatment of this condition.


Adjuvant arterial embolization in the treatment of benign primary bone tumors in children. This report presents an initial clinical experience with arterial embolization as adjuvent therapy in the surgical treatment of selected benign primary bone tumors in childhood. Embolization was dramatically effective in 4 children with spinal or pelvic vascular tumors. This technique facilitated local surgical resection and/or curettage. No child had evidence of local recurrence. Three of the 4 children had spinal cord or nerve root compression resulting in various degrees of paralysis prior to surgery. All treated patients had complete recovery from their paralysis. There were no complications of embolization or surgery. The treatment of benign primary bone tumors of the spine and pelvis is immeasurably improved by the adjuvant arterial embolization procedure. The immediate surgical treatment of these difficult tumors now becomes feasible with the greatly diminished blood flow resulting from embolization.


Routes of infection. A study of using "tracer particles" in the orthopedic operating room. Wound irrigates and tissue samples were cultured from clean orthopedic wounds at the conclusion of 280 orthopedic operations. The surgeons used a laminar flow unit and took extra precautions against wound contamination although personnel exhaust systems were not used. It was possible to culture residual organisms but difficult to trace the source of these by bacteriological methods. Artificial or "tracer" particles which could be applied to patient or surgeon were retrieved from the wound and suitably stained. Using albumin microspheres it was possible to identify and differentiate "patient-derived particles" from "surgeon-derived particles" in the majority of all wounds. Contamination from the surgeon was significant even under near optimum operating room conditions. These techniques are useful for development of control measures for residual wound contamination in orthopedic operating rooms.


Computerized tomography in orthopedic surgery. Computerized tomography has been demonstrated to be highly effective and accurate in delineating soft tissue and bony cross-sectional anatomy. The technique is very helpful in: (A) delineating the 3-dimensional extents of destructive lesions; (B) defining the nature of lesions by revealing their tissue densities and invasive characteristics; and (C) delineating the cross-sectional anatomy of complex geometric lesions; for example, fractures of the pelvis and spine. These features enable the orthopedic surgeon to better diagnose pathological lesions, plan surgical procedures, screen patients for metastases, and facilitate percutaneous biopsy or aspiration of difficult anatomic sites. While these applications are becoming well established, additional uses are under investigation in the areas of trauma, and in clinical research of metabolic bone disease.


Osteoporosis of the spine, pelvis and hand. A comparative study in a femoral neck fracture series. In a comparative study of the degree and prevalence of osteoporosis in the hand, pelvis and spine of a group of femoral neck fractures in the elderly, it was noted that spinal osteoporosis was much more frequent and appeared much earlier than pelvic osteoporosis. Similarly, a one way correlation existed between osteoporosis of the hand and spine. No relationship was noted between osteoporosis of the pelvis as measured by our criteria and by the Singh technique.


Irreducible acute anterior dislocation of the shoulder: case report. A 91-year-old woman presented with an acute anterior dislocation of the shoulder which could not be reduced by closed manipulation. Open reduction demonstrated a fresh dislocation which could not be reduced until the subscapularis muscle was divided. Only 2 previous cases of irreducible anterior dislocation of the shoulder seem to have been reported in the recent or readily available literature.


Arthrodesis of the shoulder: posterior approach. Shoulder arthrodesis through the posterior approach in 6 patients with the average follow-up of 20 months has been described. There were no surgical complications. In all cases the position of the arm was determined clinically and placed in 20 degrees abduction, 30 degrees forward flexion, and 40 degrees internal rotation.


In vivo effects of axial loading on healthy, adolescent spines. Five healthy adolescents were studied using a three-dimensional radiographic technique to analyze the in vivo effects of standing, supine and supine Cotrel traction positioning on the orientation of spinal segments. In general the configuration of these spines was found to be relatively unaffected by changes in subject position and column loading. The major effects of supine positioning appeared to be lessening of standing lumbar lordosis while supine traction tended to diminish this effect. Measurement of rotation relative to a common reference body, L4, was influenced by the degree of AP and ML wedging throughout the column. The standing curve was found to be slightly rotated by a small but constant amount at each level and tended to derotate as a whole with supine and supine traction positioning. Measurement of successive intervertebral rotation showed effects independent of wedging with each vertebral body randomly rotated and unaffected by subject orientation. With the exception of central vertebral disk heights, all parameters measured possessed relatively wide limits of variability which appeared to be the result of true intersubject scatter as opposed to measurement error.


Spondylolisthesis resulting from osteogenesis imperfecta: report of a case. Spondylolisthesis resulting from osteogenesis imperfecta has been very rarely documented in the literature. The possibility that osteofragility of the isthmus of the fifth lumbar vertabral can cause spondylolisthesis is noteworthy in the case of a 40-year-old man with trias fragilitas ossium hereditaria.


Use of the infrapatella strap in the treatment of patellofemoral pain. The spectrum of patellofemoral disorders ranging from chondromalacia of the patella to degenerative arthritis is a difficult, often vexing problem. Many methods of treatment, both surgical and nonsurgical, have been used without uniform or predictable success. The infrapatella strap, a new concept in nonsurgical management of patellofemoral pain, can be effective in 77% of patients. Its simplicity and comfort, patients' acceptance, and the apparent lack of contraindications when it is worn as instructed justify further clinical trials.


Serotonin metabolism and its enzymic activities in joint diseases. In order to clearly understand the synovial metabolic pathway of 5-HT, which is interesting as an inflammatory mediator and a pain producing substance, in patients with RA and with OA, determinations were made of 5-HIAA levels and of the activities of MAO-A and MAO-B, in the synovial fluid and the blood. With respect to 5-HIAA levels, there was no significant difference in the synovial levels between patients with RA and those with OA, although higher values were obtained in the plasma of patients with RA. A correlation was found between synovial and plasma levels in both diseases. In patients with RA, 5-HIAA levels tended to increase in both levels of the synovial fluid and the plasma in higher stages. The activities of MAO-A and MAO-B in the synovial fluid were found to be lower in patients with RA than in those with OA. The MAO-B activity in the synovial fluid increased in higher stages and correlated with ESR in patients with RA. In patients with RA the efflux of 5-HIAA from the synovial fluid was reduced. No remarkable changes occurred in the permeability of 5-HIAA. The ability to inactivate 5-HT was lower than in OA. The determination of synovial MAO-B activity is useful in diagnosing the status of the patient with respect to rheumatoid arthritis.


Electron microscopic study of the effects of calcitonin on bone cells and their extracellular milieu. This is a scanning and transmission electron microscopic study of the changes produced by small doses of calcitonin (0.15 mU/g body weight) in the lining cells and their microenvironment at the endosteal surfaces of the tibia of neonate rats. The techniques used included "freeze substitution" preparation, staining with lead acetate, and with lanthanum added to the fixative. Rats were sacrificed 5, 15, and 30 minutes after subcutaneous injection of salmon calcitonin. The following observations were made; within 5 minutes following calcitonin injection, the response of the endosteal lining cells included increased numbers of microvilli and surface blebs. Cell contraction was apparent, including an irregular appearance of the plasma membrane and enlarged intercellular channel size, though cell-to-cell contact still occurred. By 15 minutes, following hormone injection, the cells were returning to normal morphology and were in close contact with each other. Calcitonin caused a marked accumulation of lanthanum around osteocytes and in bone fluid adjacent to lining cells. The lanthanum was found in large aggregates and appeared to "clump." Following "freeze substiuttion" preparation, the edge of the osteoid was bordered by what appeared to be mineral aggregates. We conclude that bone lining cells and osteocytes respond rapidly to low doses of calcitonin, thereby suggesting that they play a role in the physiological action of the hormone. This function includes a modification of the fluid microenvironment of these cells, possibly providing a site for temporary storage of calcium.


Medial epicondylectomy for ulnar nerve compression syndrome at the elbow. Nineteen patients were evaluated 6--17 months after medial epicondylectomy (22 extremities) for ulnar nerve compression syndrome at the elbow. Medial epicondylectomy removes the prominence against which the ulnar nerve can be traumatically compressed and no operative handling of the nerve is necessary. Pre- and postoperative nerve conduction velocities were combined with subjective and objective evaluations of all patients. Statically significant correlations were found between the result and the postoperative nerve conduction velocity and the result and the per cent change of nerve conduction velocity. Ten extremities were classified as good results (48%), 4 as fair results (17%), and 8 as poor results (35%). Four limbs in the poor category and one limb in the fair category had electrical evidence of proximal compression neuropathy which compromised the end result. Exclusion of the patients with evidence of proximal neuropathy would yield 76% good or fair results. Measurement of ulnar nerve lengths in fresh cadavers demonstrated that ulnar nerve conduction velocity studies should be performed at 70 degrees of elbow flexion if accurate pre- and postoperative velocities are to be obtained.


Banded structures in human nucleus pulposus. We studied 20 intervertebral disks from cervical, thoracic, and lumbar levels from patients 12 hours to 55-years-old by electronmicroscopy. Tissue was obtained at operation from 10 patients with scoliosis and 6 with herniation of the intervertebral disk. Four intervertebral disks were removed at autopsies performed within 4 hours of death. Banded structures distinct from native collagen were present in the nuclei pulposi of all intervertebral disks but not in the annuli fibrosi. These structures may be an unusual form of collagen, however they closely resemble extracellular banded structures found in frog muscle spindle that may form from find filaments when the muscle spindle increases in length.


The collagenous architecture of articular cartilage. Correlation of scanning electron microscopy and polarized light microscopy observations. The localization and directional orientation of collagen fibers in articular cartilage is demonstrated by scanning electron microscopy and polarized light microscopy. Vertical sections of articular cartilage show different directional orientations of collagen fibers through all zones of cartilage depending upon whether the sections are parallel or perpendicular to the cleft pattern produced when the surface of articular cartilage is pierced with a round pointed awl. Sections parallel to the cleft axis show a significant population of oblique collagen fibers which are not seen in sections perpendicular to the clefts. These oblique fiber groups show a progression from nearly radial to nearly tangential orientation from deep to more superficial zones, with the most abrupt directional change seen through the transitional zone. Within the transitional zone there is a narrow band having no vertical or horizontal collagen fibers and in which collagen fibers intersect predominantly at angles ranging between 45 and 135 degrees. The number of chondrocyte lacunae per unit area is greater in sections parallel to the cleft axis compared to perpendicular sections by a factor of approximately 1.6:1. There is therefore a greater relative number of chondrocytes in the plane of section having the greatest abundance of oblique collagen fibers, suggesting a cellular basis for the collagenous architecture observed. The results are consistent with published biophysical data relating tensile and swelling properties of all zones of articular cartilage to the cleft axis.


The safety of cement fixation in the cervical spine. Studies of a rabbit model. Immediate postoperative ambulation of patients with terminal neoplastic disease of the cervical spine can be permitted by vertebral stabilization with wire reinforced with polymethylmethacrylate. Precautions are necessary to avoid a temperature rise during cement polymerization and prevent vasular or nerve damage. Experiments on 20 rabbits and 2 human cadavers indicate that temperature at the cement-lamina interface can rise as high as 90 degrees while temperature under the intact lamina measures only 50 degrees. Precooling and insulation with Gelfoam may prevent heat injury to spinal cord.


Muscle forces in the posterior thoracic spine. Using a three-dimensional model, the theoretical maximal forces that can be generated by electrical stimulation of several posterior thoracic muscles have been analyzed to investigate the kinesiology of scoliosis. None provides a pure lateral bending moment, and most exaggerate lordosis. None satisfactorily generates a rotary force for correction of scoliotic deformity. Although maximum muscle contraction can ideally produce lateral bending moments of the same magnitude as the Milwaukee brace, current techniques do not cause continuous, complete muscle contraction. The best muscle studied for electrospinal intrumentation is the lateral erector spinae. Multiple sites of stimulating electrodes are probably necessary. None of the individual muscles studied is ideal. Further investigation should be directed to the stimulation of anterior thoracic muscles.


Sacral agenesis: a clinical evaluation of its management, heredity, and associated anomalies. In the child born with sacral agenesis, the management of arthrogrypotic-like deformities, spinal and multisystem abnormalities poses several problems to the orthopedist. A clinical evaluation was undertaken on 17 patients and available parents in an effort to define better the heredity and proper management of this disorder. Flexion contractures of the hips and knees adversely affect ambulation potential and are rather resistant to standard treatment. The presence of protective sensation and proprioception, though, warrants aggressive attempts at correction, Subtrochanteric amputations are not necessary to achieve a functional ambulator. Spinal-pelvic instability does not preclude functional ambulation. In fact, there may be some benefit in maintaining motion in this region. Abolishment of spinal-pelvic motion by surgical fusion in the presence of hip contractures could impair sitting ability and the ability to walk upright. Congenital vertebral anomalies in the remainder of the spine, including the neck, occurred in 12 patients. Four patients had idiopathic-like curves. Only one patient had a normal spin above the level of agenesis. From an analysis of families, there was no obvious genetic association. Finally, the high frequency of multisystem associated congential abnormalities will necessitate a team approach to these patients.


Operative treatment of spine deformity in osteogenesis imperfecta. There has been little mention in the literature of scoliosis associated with osteogenesis imperfecta. The purpose of this study was to investigate the problem of spine deformity in a series of osteogenesis imperfecta patients and to review the operative treatment of 8 patients. A series of 49 patients (ranging in age from 8 months to 57 years, average 12 years) with osteogenesis imperfecta were studied. Thirty-five (71%) of these patients had scoliosis ranging from 7 degrees to 105 degrees (average 42 degrees). The more severely involved patients (OIC and OITI groups) demenostrated a higher incidence (80%) of scoliosis and a greater average degree of curvature (42 degrees) as compared to the mildly involved (OITII) group with a 50% incidence of scoliosis with an average curvature of 26 degrees. Attempts to control these curves by bracing have been difficult and usually had to be abandoned. Eight of these patients underwent spine stabilization in an attempt to control curve progression. All 8 patients had posterior spine fusions. One of these patients had an anterior fusion preceding the posterior fusion because of a significant kyphotic deformity. Harrington instrumentation was used in 5 patients. One patient could not be instrumented secondary to severe osteoporosis while the remaining 2 patients were treated by the Risser technique. Postoperatively, either cast or brace protection was used. Only minimal improvement in the curves was achieved. Spine stabilization rather than curve correction is the goal of spine fusion in osteogenesis imperfecta. An important finding was that there was no change in the pre- and postoperative activity and ambulatory status in these patients. Preliminary follow-up (9-12 months) in all 8


The thoracic suspension orthosis.

The thoracic suspension orthosis. Five year's experience with the thoracic suspension orthosis at Newington Children's Hospital has shown it to be an effective and very useful adjunct in the management of neuromuscular spinal deformity. The orthosis converts the thorax into a weight-bearing structure, thereby reducing the vertical load on the spine and allowing the abdomen and pelvis to act as a corrective distraction force. Fifty-nine of the 64 patients reported here have successfully used the orthosis to control spinal deformity and improve their functional status. Analysis of these 59 patients and the 5 treatment failures has resulted in identification of the specific indications, prerequisites, techniques, precautions, and contraindications necessary for the achievement of stated treatment objectives, often with dramatic success.


The orthopedic aspects of the fetal alcohol syndrome. Eight cases of the fetal alcohol syndrome are presented with emphasis on their frequent orthopedic anomalies, i.e. hypoplastic toenails (100%), shortened fingers, usually the fifth (75%), radioulnar synostosis, camptodactyly of fingers, clinodactyly of toes, and flexion contractures of the elbow (all 50%). These are in addition to 7 other orthopedic anomalies observed less frequently and some 18 general characteristics had an extensive endocrine, biochemical and genetic work-up and no abnormalities were found to explain the snydrome other than the teratogenicity of the maternal alcohol abuse. Since the orthopedist may be the first physician to see these patients, diagnosis of these musculoskeletal anomalies should include a social history and investigation for fetal alcohol syndrome.


Diagnosis of ruptured bladder during a 99mTc-DTPA renal study: new indications for radionuclide cystography? Radionuclide cystography, which is currently used to evaluate vesicoureteral reflux, has also been used to detect perirenal and perivesical urine leakage. We report a case of intraperitoneal bladder rupture and describe potential indications and advantages of cystography for detection and evaluation.


Severe complication of surgical treatment of congenital pseudarthrosis of the clavicle. Congenital pseudarthrosis of the clavicle, as observed in a review of the literature, is a rare condition of uncertain etiology which usually presents on the right side. Four of 10 cases were treated by surgical repair of the pseudarthrosis with excision of the non-union and internal fixation with a Steinmann pin and cancellous bone graft. A major postoperative complication in one case consisted of an acute massive neuropraxia of the brachial plexus (recognized 6 hours postoperatively), and was successfully treated by immediate removal of the internal fixation. Ten months postoperatively, the patient was experiencing only minimal weakness of the right opponens muscle. Roentgenograms at this time showed that the pseudarthrosis had healed but with angulation of the clavicle.


Decreased splenic perfusion without functional asplenia. Although functional asplenia may be associated with decreased splenic perfusion, two cases are presented which illustrate that the converse is not necessarily true. That is, two patients with markedly reduced splenic perfusion still showed splenic extraction of radiocolloid. These cases clearly demonstrate the dissociation of splenic blood flow and the radiocolloid extraction processes. Factors which might have contributed to the decreased perfusion are discussed.


Legg-Calvé-Perthes disease: Results of discontinuing treatment in the early reossification phase. The major controversy in Legg-Calvé-Perthes disease concerns its treatment. All authors recognize the need for containment of the femoral head but do not agree on the method of containment. Surgical containment is constant, does not require an endpoint for discontinuing treatment and has a short treatment period. Conservative treatment, however, produces comparable results, avoids operative and anesthetic complications but requires prolonged immobilization. The concept of Ferguson and Howorth can be validated and indicates that when early subchondral reossification is present on both the anteroposterior and lateral roentgenograms that conservative containment treatment can be safely discontinued thus shortening outpatient time to 12 months or less. The results of 165 hips undergoing conservative treatment and 27 who received surgery are analyzed. Eighty-one conservatively treated hips were mobilized early and followed for an average of 5 years. Their results were identical to those treated until the time of complete restoration of the capital femoral epiphysis. This reduction in outpatient treatment and the decrease in potential complications minimizes several of the major arguments in favor of surgical management.


Myositas ossificans progressiva associated with severe scoliosis. This is an 11 year follow-up of a patient with myositis ossificans progressiva and severe scoliosis, an association that seems not to have been reported previously. A progressive increase of the curve occurred even after maturity. Early instrumentation and fusion should be considered on any similar case, with excision of ossific mass and its use as bone graft if technically feasible.


S-C joint disruption in an infant.

S-C joint disruption in an infant. An anterosuperior sternoclavicular disruption in a 7 month old female was caused by trauma. Good results were observed by concervative managment.


Localization of 99mTc-methylene diphosphonate in skin lesions of pseudoxanthoma elasticum. Increased uptake of 99mTc-methylene diphosphonate (MDP) is demonstrated in a patient with pseudoxanthoma elasticum (PXE) at the affected site. PXE is a hereditary disease with variable expression. Calification of dermal elastic fibers is a characteristic feature of affected skin. Recently, apatite crystals were identified in the affected skin of the patients with PXE. The mechanism of uptake of 99mTc-MDP is probably related to chemisorption of the tracer onto hydroxyapatite crystals in the affected dermis.


Prognosis in septic arthritis of the hip in children. Thirty-eight children (39 hips) with septic arthritis have been reviewed in an effort to determine the factors most important to prognosis of the hip joint. The younger patients, 3 or more years later, had poorer results by roentgenographic classification. This was particularly true of patients under one year of age. Longer duration of disease from clinical onset to initiation of therapy also resulted in a poorer result. The outcome could not be clearly correlated with the causative organism or with open as opposed to closed treatment although the policy of management was strongly biased to open drainage. Sixty per cent of the infections were caused by Staphylococcus aureaus and the majority of the other cases by Streptococcus pyogenes and Hemophilus influenzae. The nonstaphylococcal organisms may be less destructive to the femoral head in infants.


"Plain film" diagnosis of ovarian cyst.

"Plain film" diagnosis of ovarian cyst. Nuclear images frequently include large areas of the patient which are unrelated to the specific organ system under study. The alert interpreter may discover clinically significant information from these portions of the image. This report describes the diagnosis of an ovarian cyst that was suggested by an absence of activity in the pelvis noted on routine rectillnear bone scan.


Epiphyseal osteochondroma of the anterior cruciate ligament. An 8-year-old Black boy complained of pain, swelling, and a decreased range of motion in the knee. One arthrotomy operation was reported to show a normal knee joint. Six months later, a second arthrotomy demonstrated an osteochondroma growing from the epiphysis into the anterior cruciate ligament. Epiphyseal osteochondroma should be added to the working differential diagnosis on children with effusion and decrease of knee motion.


Fibular transfer for congenital absence of the tibia. In patients with congenital absence of the tibia, construction of a knee joint by transferring the fibula under the femoral condyle gives satisfactory results, provided a strong quadriceps is present. In the rare patient with an associated proximal focal femoral deficiency on the same side, even in the absence of a strong quadriceps, this procedure with a fibulofemoral fusion will give a longer stump, allowing better prosthetic fitting. The procedure is performed as early as the first year of life.


Sudden infant death syndrome risk factors. Prospective data review. Prospective data from a population of newborn infants were searched for risk factors for Sudden Infant Death Syndrome (SIDS). Maternal smoking, younger maternal age, short intervals between pregnancies, gestational age of less than 40 weeks, birth weight of less than 3000 g, lower socioeconomic status and male sex were factors found to be associated with SIDS. Race, blood type, maternal hemoglobin level, placental abnormality and newborn condition were not associated with SIDS in this population. Scoring systems to predict which infants will die of SIDS are not yet sensitive enough for clinical use.


Sudden infant death syndrome. Acute loss and grief reactions. This paper provides guidelines for health professionals in dealing with the particular grief reactions experienced by families of babies who die of the sudden infant death syndrome (SIDS). Time and privacy are needed to work through the anguish of grief. However, the SIDS families who cope best are those who are also guided throughout their grieving process by a caring physician who is comfortable in his supportive role. It is hoped that through an increased understanding of acute loss, the medical community will be better able to help SIDS parents and their surviving children regain their psychologic energy.


Sickling crises and altitude. Occurrence in the Colorado patient population. Seventy-five black patients with sickle hemoglobinopathies who are followed by the Colorado Sickle Cell Treatment and Research Center, and 172 of their family members were evaluated by retrospective interview for the occurrence of sickling crises when traveling in the Rocky Mountains or by aircraft. Twenty per cent of 39 patients with sickle cell anemia (Hgb SS) (Hgbs S/C and S/T) have developed crises when traveling in the mountains above 2000m. Vaso-occlusive crises predominated in the SS group and splenic crises occurred primarily in those with Hgbs S/C and S/T. Approximately 20 per cent of those with S/C and S/T, but none with SS, had crises when flying in pressurized aircraft. Among 103 family members with sickle cell trait (Hgb AS), no significant risk of developing crises could be identified with either mountain or pressurized aircraft travel.


A re-evaluation of intersubject variation in enzyme induction in man. It has previously been suggested that subjects who are initially slow metabolisers of drugs have a greater potential for induction of their drug metabolising enzymes than subjects with initial high rates of metabolism. This inference is based on observations made of changes in half-life of antipyrine. The purpose of this presentation is to reanalyse data previously presented in the literature with reference to clearance, a more precise estimate of drug metabolising activity, and half-life a parameter derived from both clearance and distribution. In one study in non-obese subjects, approximately 80% of intersubject variation in the change of total antipyrine clearance can be explained by differences in body size, particularly differences in liver volume. Furthermore, the relationship between initial antipyrine half-life and the percentage change in antipyrine half-life following induction can be explained by the association between each parameter and body weight. These observations imply that the potential for enzyme induction, and therefore for drug interactions based on enzyme induction, is present in all subjects and that intersubject variance in steady-state drug concentrations are as wide following induction as before induction.


Plasma protein binding of etomidate in patients with renal failure or hepatic cirrhosis. The influence of renal failure and of hepatic cirrhosis on the plasma protein binding of etomidate, an intravenous anaesthetic agent of basic nature, has been investigated. The percentage of free etomidate in plasma containing 1 microgram/ml was markedly increased in patients with renal failure and in patients with hepatic cirrhosis, when compared with a group of healthy volunteers (43.4 +/- 2.9% and 44.2 +/- 2.1 versus 24.9 +/- 1.4%). This decrease in binding correlated inversely with serum albumin levels in both conditions (r = -0.88 and r = 0.72, respectively) but a slight decrease in the amount bound per mole of albumin was also apparent in both types of disease.


Isolated acute meningococcal arthritis.

Isolated acute meningococcal arthritis. Isolated, acute, suppurative meningococcal arthritis is reported in a five-month-old infant. It should be differentiated from arthritis associated with chronic meningococcemia and acute systemic meningococcemia.


The white cell ratio in the very low birth weight infant. The purpose of this study was to assess the usefulness of the white cell ratio of immature neutrophils (PMNs) to total (immature plus mature) PMNs as an indication of infection in the very small premature infant. We retrospectively reviewed the charts of 59 premature infants less than or equal to 1,250 g admitted to our Newborn Intensive Care Unit over a one-year period who had at least one white count determined. Twenty-three were born after rupture of membranes for greater than or equal to 24 hours (PROM), 47 had a one-minute Apgar score less than or equal to 6 and 31 had a five-minute Apgar scores less than or equal to 6, 38 had respiratory distress syndrome (RDS), and 4 had confirmed infection. Thirty-one of the infants had a ratio greater than or equal to .15 in the first day of life, a value which has been suggested in the literature as being abnormal and an indication to suspect sepsis. This ratio bore no statistical relationship to PROM, low Apgar scores, or RDS. We analyzed these same relationships using a ratio greater than or equal to .25, another ratio derived from data in the literature which has been said to suggest infection. No statistical correlation was found for low Apgars or RDS, but there was a significant relationship between PROM and attainment of a ratio greater than or equal to .25 (p less than .005). It is notable that 2 out of the 4 infants with infection had a ratio less than .15. We wish to cast doubt on the applicability of the currently defined WBC ratios in the literature as they apply to the infant with birth weight less than 1,250 g and emphasize the apparent effect of PROM as a factor upon these ratios.


Chronic foreign body aspiration diagnosed by lung scan. The case of a two-year-old child with foreign body aspiration is presented. It was complicated by a delay in diagnosis and treatment. Lung scan was helpful in eventually establishing the diagnosis. Key points in the management of patients with foreign body aspiration are reviewed and pathophysiologic mechanisms are discussed.


Anuria in childhood due to bilateral urolithiasis. A report of four cases. Four children with anuria due to occlusion of both ureters by calculi are presented. A plain film of the abdomen revealed faintly radiopaque urinary calculi bilaterally in three patients. In the fourth case, one calculus was visualized in the right ureter, but further contralateral exploration showed an obstructing ureteral calculus in the left ureter as well. It is concluded that in children with acute anuria, the possibility of bilateral ureteral obstruction due to calculi should be the physician's first consideration.


Plasma clearance of propranolol and sotalol and hepatic drug-metabolizing enzyme activity. The role of hepatic drug-metabolizing enzyme activity for plasma propranolol and sotalol levels was investigated in 68 patients with hypertension or angina pectoris by comparing elimination rate with antipyrine kinetics and cytochrome P-450 content in the liver. All subjects were resistant to or had hepatotoxic reaction to previous treatment. Plasma antipyrine clearance and cytochrome P-450 content in biopsies were related to propranolol elimination from plasma, the best fit being obtained with the clearance values. Sotalol plasma clearance was not related to any indirect or direct reflector of the hepatic drug-metabolizing enzyme system. The results demonstrate that plasma clearance of the short-acting beta blocker, propranolol, depends on the activity of hepatic drug-metabolizing enzyme system and indicates a trial with a drug such as sotalol which is not dependent on liver metabolizing capacity.


Presystemic and systemic glucuronidation of propranolol. The relative importance of presystemic and systemic glucuronidation of propranolol was examined in normal subjects given single oral and intravenous doses of propranolol. The areas under the plasma concentration--time curves (AUCs) of propranolol glucuronide (PG), 41 +/- 15 ng . hr/ml, and propranolol, 48 +/- 15 ng . hr/ml, were of the same order after the intravenous dose (0.05 mg/kg). After oral doses of 20 and 80 mg, the AUCs of PG were 302 +/- 105 and 1,398 +/- 409 ng . hr/ml; these were 7 times the AUCs of propranolol, 44 +/- 15 and 220 +/- 38 ng . hr/ml. The time lapse to peak concentration, 1.5 to 3.0 hr, and the plasma half-life, 3.2 to 3.7 hr, were the same for PG and propranolol. These results demonstrate glucuronidation as an important determinant of propranolol bioavailability.


Maternal, fetal, and neonatal metabolism of lidocaine. We investigated the metabolism of lidocaine to its active metabolites--monoethylglycinexylidide (MEGX) and glycinexylidide (GX)--in the mother, fetus, and neonate. The study population included normal patients and their infants delivered either vaginally or by cesarean section. A group of infants of mothers in whom pudendal anesthesia was induced was also included. Using gas chromatography and mass spectrometry techniques, the concentrations of lidocaine, MEGX, and GX were determined in maternal plasma during labor, in umbilical cord venous and arterial plasma at delivery, and in maternal and neonatal urine for 3 days post partum. The results indicate the following: In maternal plasma, MEGX rises throughout labor and GX is usually detectable within an hour of medication; in cord blood plasma the levels of lidocaine, MEGX, and GX suggest fetal metabolism of lidocaine; and in neonatal urine, the relative levels of parent compound and metabolites confirm lidocaine metabolism by the neonate.


Alterations in the disposition of differently cleared drugs in patients with cirrhosis. We have compared the disposition of antipyrine orally (15 mg/kg) and the new antiarrhythmic drug lorcainide intravenously (1.5 mg/kg) in 8 patients with alcoholic cirrhosis. Antipyrine (AP) serves as a model drug for drugs which are eliminated independently of liver blood flow and lorcainide (L) elimination as a model for drugs which depend on liver blood flow. Since in healthy subjects elimination half-life (t 1/2) of L increased with age (r = 0.68, p less than 0.01) due to parallel change in the volume of distribution (r = 0.52, p less than 0.05), its disposition had to be compared to age-matched controls. Elimination of both AP and L was impaired in cirrhotic patients, expressed either in terms (mean +/- SD) of t 1/2 (AP = 26.8 +/- 15.0 hr and 12.3 +/- 1.8; L = 12.5 +/- 4.5 hr and 7.7 +/- 2.2 hr, p = 0.002) or of clearance (Cl) (AP = 21.9 +/- 7.9 ml/min and 41.7 +/- 5.5 ml/min; L = 814 +/- 144 and 1002 +/- 304 ml/min, p = 0.06). While the alterations in plasma Cl were great for AP, they were smaller for L. This suggests that elimination of drugs in cirrhotic patients is associated with relatively more impairment of enzyme activity than of hepatic blood flow. The slightly decreased Cl of L in patients with alcoholic cirrhosis would suggest that L should be carefully handled in patients with dysfunction of the liver.


Kinetics of intravenous mezlocillin in chronic hemodialysis patients. The kinetics of intravenous mezlocillin was studied in 8 patients with creatinine clearances under 7 ml/min who were undergoing chronic hemodialysis. Kinetic parameters were determined using a 2-compartment linear model. The mezlocillin serum half-life (t 1/2) in these patients ranged from 2.9 to 7.8 hr (mean, 5.4). The t 1/2 decreased to 1.57 +/- 0.09 hr during dialysis. Approximately 18% of the dose was recovered in the dialysate in 4 hr of dialysis. There was a 30% reduction per hour in serum concentration. The kinetics of mezlocillin, due to removal by nonrenal mechanisms, more closely resemble the kinetics of penicillin G and ampicillin than of carbenicillin and ticarcillin. A dosage schedule for use of intravenous mezlocillin in patients undergoing hemodialysis is presented.


Rectal and oral absorption of methylprednisolone acetate. Rectal absorption of methylprednisolone acetate and oral absorption of methylprednisolone and methylprednisolone acetate were investigated in a single-dose 3-way crossover study of 12 normal male volunteers. The median value of bioavailability (relative to oral dose) of methylprednisolone acetate based on unchanged methylprednisolone plasma levels was 14.2% after rectal administration, suggesting that the drug exerts its therapeutic effect topically rather than systemically. In contrast, the median of total radioactivity in urine (as a percentage of rectal dose) was 34.3% (range, 4.52% to 58.8%), suggesting partial bacterial metabolism in the rectum prior to absorption. Mean bioavailability (relative to oral administration of methylprednisolone acetate) of methylprednisolone after oral administration was 89.9%, indicating somewhat better systemic availability of the ester than the alcohol. The average apparent elimination rate constant for methylprednisolone after oral administration of both ester and alcohol was 0.290 hr-1, corresponding to a half-life of 2.39 hr.


Chlordiazepoxide and oxazepam disposition in cirrhosis. When disease impairs clearance of drugs, multiple-dose therapy may result in cumulation. The disposition of chlordiazepoxide (CDX), 50 mg infused intravenously over 10 min, was studied in 14 normal subjects and in 11 patients with biopsy-proven cirrhosis. In the normal subjects, mean (+/- SE) kinetic parameters were: t 1/2 beta, 10.0 (+/- 0.9) hr; Vd, 0.38 (+/- 0.04) l/kg; clearance, 0.54 (+/- 0.13) ml/min/kg. Clearance of total drug correlated inversely with serum albumin concentration in normal subjects (r = -0.63). Values in cirrhotic patients were: t 1/2 beta, 34.9 (+/- 8.7) hr; Vd, 0.34 (+/- 0.024) 1/kg; and clearance, 0.185 (+/- 0.34) ml/min/kg. Desmethylchlordiazepoxide (DMCDX), the major metabolite of CDX, appeared in blood of cirrhotic patients less rapidly than in normal subjects. Severity of liver disease did not indicate the impairment of CDX clearance. In 5 of the same cirrhotic patients, mean t 1/2 beta for oxazepam (7.1 +/- 1.0 hr) was 27% longer than in control subjects (5.6 +/- 0.7 hr); the difference is not significant. On kinetic grounds oxazepam may be preferable to chlordiazepoxide in cirrhotic patients since its elimination kinetics are not greatly altered in cirrhosis.


Intravenous phenobarbital therapy in barbiturate and other hypnosedative withdrawal reactions: a kinetic approach. Phenobarbital (0.03 to 0.04 mg/kg/min) was infused intravenously in 7 patients with clinical hypnosedative withdrawal reaction until patients slept but were arousable. The infusion time to reach this clinical end point was 7.8 +/- 1.1 hr (mean +/- SEM), the total dose was 992 +/- 144 mg, and the peak serum phenobarbital concentration was 26.1 +/- 5.1 micrograms/ml. A user of minimal hypnosedatives required 54% less phenobarbital and 65% lower concentration than any of the abusers to reach an equivalent state of intoxication. The mean serum half-life (t 1/2) was 57.5 +/- 4.9 hr for hypnosedative abusers and 86 +/- 3 hr for 8 normal volunteers (p less than 0.001). Only the patient with the shortest t 1/2 (36.4 hr) required oral phenobarbital supplements to prevent withdrawal symptoms. Dosage supplements required can be calculated from the postinfusion rate of fall of serum phenobarbital. Slow infusion of large amounts of phenobarbital provides a safe, efficacious single-dose treatment.


Techniques for plasma protein binding of demethylchlorimipramine. The cerebrospinal fluid (CSF) and plasma levels of demethylchlorimipramine (DMCI) were determined during treatment of depression or obsessive-compulsive disorders with chlorimipramine. In 18 patients the mean CSF/plasma ratio of DMCI was 2.6% +/- 0.7 SD with fourfold variation (1.1% to 4.0%). In spite of this variation, the levels in CSF and plasma at steady state correlated closely (r = 0.91; p less than  0.001). With equilibrium dialysis for the determination of the protein binding of DMCI, a much higher free fraction was found in patients (8.0 +/- 1.6%) and in control subjects (8.2 +/- 1.4%). It was shown that part of the plasma binding capacity was lost during the incubation. Results obtained by ultrafiltration (3.9 +/- 1.0% unbound drug) were closer to the in vivo results, but this method also had disadvantages; much of the drug was absorbed on the ultrafiltration dialysis membrane. Our results suggest that there is a need for care in the selection of a technique for studies of drug protein binding.


The role of computed tomography in the management of testicular teratoma. CT scans of the lungs, mediastinum and abdomen have been performed in 65 patients with malignant teratoma between August 1977 and June 1978. CT is superior to conventional radiology in detecting pulmonary metastases and mediastinal lymphadenopathy. It is a valuable technique for defining the full extent of para-aortic nodal disease and provides more information than lymphography alone. In this series sequential CT scans have been used to monitor treatment response to detect relapse and to assess operability of demonstrable residual disease.


A rotation technique for irradiation of the bladder and the results obtained. An argument is advanced for the use of partial rotational techniques for the treatment of carcinoma of the bladder. One hundred and seventy cases are analysed: the majority were T3 solid transitional cell lesions with an overall (corrected) survival rate of 24.7%. Salvage cystectomy produced a four-year survival rate of 40% when performed within six months of the radiotherapy.


The dose-time relationship in the radiotherapy of carcinoma of the cervix uteri: an application of the CRE formalism. A correlation could be obtained between the likelihood of control of central and nodal disease and the corresponding local CRE levels attained in a group of 79 cases of carcinoma of the cervix uteri treated according to a multistage protocol involving a combination of external telecobalt irradiation and intracavitary radium application. A nodal CRE level of 1700 reu and a central CRE value of 2900 reu seemed to be optimal for control of modal metastases and central disease respectively. These CRE levels seemed to be well tolerated even if salvage surgery had to be performed.


Isoeffect lines using TDF and CRE concepts. In most of the radiotherapy centres the treatment planning is based on isodose lines. Isoeffect lines are also being drawn based on the concepts of TDFs and CREs. It was aimed in this work to find out whether the isoeffect lines based on the concepts of TDFs, CREs and the physical isodose lines are identical in all the treatment situations. Isoeffect lines for a few treatment schedules involving treatment of carcinoma of the bladder, treatment of cancer of the uterine cervix by combined intracavitary and external beam therapies and intracavitary therapy alone have been obtained and compared in the present study. The effect of treatment mode on the isoeffect lines is also studied. It is found that the isodose curves and the isoeffect lines using the TDF and CRE concepts are not identical in all situations. Therefore, the ultimate treatment plans based on theses isoeffect lines will not be exactly the same. The dependence of the isoeffect lines with the variation of the exponents of time and number of fractions used in the empirical relationship for NSD have also been investigated. Clinical trials have been initiated in the case of cancer of the bladder and cervix uterus based on the isodose curves and the isoeffect lines using CRE and TDF concepts.


Needle localisation of non-palpable breast lesions. Localisation of non-palpable breast lesions using a simple inexpensive apparatus which can be constructed in most hospital workshops is described. A single-needle bi-plane technique is used. The details of the apparatus are given and the radiographic control of the insertion of the needle is described, particular emphasis being placed on practical details in order to assist those who are unfamiliar with the technique. The importance of localisation for the pathologist is emphasised.


Ultrasonic detection of pericardial effusions adjacent to the right atrium during routine examination of the upper abdomen. Pericardial effusions are usually detected on ultrasound by examining the heart with time--motion (T/M) or real-time equipment through a left chest intercostal space. Since fluid within the pericardium also accumulated around the right atrium, effusions can also be diagnosed by observing fluid separating the right atrium from hemidiaphragm on parasagittal scans of the right upper abdomen. In order to be certain that this space represents pericardial rather than pleural fluid, the inferior vena cava must be identified along the lower margin of the fluid space as a tubular structure traversing from the diaphragm into the right atrium. Our procedure is proposed as an ancillary approach for detecting clinica-ly unsuspected effusions during the routine examination of the upper abdomen rather than as a replacement for the usual method of visualising pericardial effusions.


Primary disorders of bone with 'spinal block'. Two hundred and thirty-two cases of compression of the spinal cord or cauda equina included 11 cases where compression was entirely due to a primary bony disorder and 20 further cases where developmental spinal stenosis was the main cause of compression. The former group consisted of two cases of Paget's disease and one each of polyostotic fibrous dysplasia, chondrosarcoma, achondroplasia, spondylo-epiphyseal dysplasia, Klippel--Feil syndrome, haemangioma of bone, primary bone reticulosarcoma, osteoporotic fracture and vertebral osteomyelitis. Three patients, with fibrous dysplasia, chondrosarcoma and Paget's disease with recurrent compression respectively, are described and the relevant literature is reviewed. The large number of primary disorders of bone which can cause cord compression are tabulated. Cord compression is a rare complication in most of these disorders but collectively they caused 13% of the cases of spinal block in this series.


Thinning of the clavicular cortex in adults under the age of 45 in osteomalacia and hyperparathyroidism. A study involving 18 patients shows that thinning of the upper cortex of the clavicle in adults under the age of 45 is most commonly due to renal osteodystrophy or coeliac disease. Cortical thinning should not therefore be regarded as synonymous with osteoporosis. Cortical thinning is usually associated with clavicular erosion in renal osteodystrophy but not in osteoporosis or osteomalacia. The radiological diagnosis of coeliac disease is suggested when thinning of the clavicular cortex is combined with air--fluid levels on abdominal radiography in a patient under the age of 45 years.


Elbow arthrography: brief technical considerations. The author describes his technique for elbow arthrography. Linear tomography is advocated as a useful supplemental technique in both single and double contrast examinations.


Tarsal bone disintegration in leprosy.

Tarsal bone disintegration in leprosy. Tarsal bone disintegration is characterised by fragmentation and progressive collapse of one or more tarsal bones. It occurs in 10% of leprosy patients, and is responsible for many severe foot deformities associated with this disease. The main cause is micro-traumata, but sensory impairment, sepsis and osteoporosis are predisposing factors. In this series of 400 consecutive patients the talus and navicular were involved most frequently (2% of 119 tarsal lesions). Treatment, including prolonged immobilisation of the foot, results in dense sclerosis of the affected bone, and leaves a functional limb. Initial radiological features include: (i) Bone fragmentation. (ii) Calcified fragments in adjacent soft tissues. (iii) Linear fractures. (iv) Progressive compression and deformity of the affected bone. (v) Loss of density of the affected bone. (vi) Flattening of the longitudinal plantar arch. Illustrative case histories are presented, and the differential diagnosis discussed.


Cleidocranial dysplasia. A family study. The incidental observation of Wormian bones in the skull and defective ossification of the public symphysis in a mildly scoliotic 12-year-old girl prompted a clinical and radiological study of members of her family. The diagnosis of cleidocranial dysplasia (CCD) was established by observing similar skeletal abnormalities in eight out of ten of them but the classical clavicular defect in only one, the last to be examined. Abnormal modelling of the medial end of both clavicles was observed in all those affected. A modelling defect of the public bones is suggested as an additional, hitherto undescribed, radiological sign. The progression with age of certain radiological features of CCD is discussed. It is suggested that this family represents an atypical variant of CCD. Such variance may be more prevalent in patients with mild scoliosis than presently suspected. A complete skeletal survey with espeical attention to the skull, pelvis and medial aspect of the clavicle and family studies may be essential for the definitive diagnosis of CCD in certain patients.


The thoracic paraspinal line: further signficance. Three hundred and seventeen cases which included 100 normal individuals have been studied for roentgen significance of the thoracic paraspinal line (TPL). The descending thoracic aorta greatly determines the course and configuration of the TPL. In a right-sided aorta, the TPL is seen on the right side as a mirror image of a left-sided TPL. Lateral deviation of the TPL and descending aorta occur as an ageing process. In systemic hypertension where there is an aortic unfolding, the TPL also unfolds and the degree of TPL deviation has a fair degree of linear relationship with the severity and duration of hypertension in young individuals. Most cases of mitral valvular disease show lateral deviation of the TPL and descending aorta. In these cases the enlarged left atrium displaces the descending aorta and hence the posteromedial border of left lung posterolaterally tangential to the vertebral column resulting in deviation of the TPL and aorta. Perioesophageal spread of carcinoma of the oesophagus into the posterior mediastinum is indicated by changes in pleuro-oesophageal interface and TPL. Mediastinal lymphadenopathy in cases of testicular tumours may be detected by discovery of TPL deviation on frontal radiographs of the thoracic spine. In extradural masses such as granulomas, abscesses and metastatic deposits, the TPL shows a localised bulge corresponding to the clinical and myelographic level of spinal compression.


The multi-channelled pylorus.

The multi-channelled pylorus. The entity of multiple pyloric channels may be congenital but the majority are acquired lesions representing fistulae secondary to peptic ulcer disease in the pyloroduodenal region. The fistula usually joins the lesser curvature of the stomach with the superior aspect of the duodenal bulb. The multichannelled pylorus produces a characteristic radiological appearance on barium mean examination with a double or split barium column in the region of the pylorus. Four cases are described and illustrated.


Renal adenomas.

Renal adenomas. In presenting five new cases of renal adenomas the authors describe the general nature of these rare tumours. If the small adenoma corresponding to microscopic forms is frequent, the large adenoma is rare and always solitary. Haematuria and pain are the most common signs. The classic criterion of non-malignancy in a solid tumour measuring less than 3 cm has no diagnostic value. From a review of the lieterature on the subject, the authors demonstrate the angio-architecture corresponding to the different types of adenoma: the tubular adenoma which is hypervascularised and well circumscribed; the papillary adenoma, often cortical, hypovascular or avascular with bordering arcade; the alveolar adenoma; the mixed forms. They stress the difficulty of radiological diagnosis and the frequency of transitional forms with cancer. The place of angiography is in the pre-operative diagnostic assessment and in defining localised anomalies in angio-architecture which can guide histological examination in the search for neoplastic foci.


Roentgenographic findings in a spectrum of uncommon tracheo-oesophageal anomalies. Roentgenographic and clinical findings in a spectrum of malformations of the trachea and oesophagus are discussed. Five previously unreported patients representing four rare anomalies of tracheal agenesis, laryngotracheo-oesophageal cleft, oesophageal atresia with a tracheo-oesophageal (T-E) fistula to the proximal oesophageal pouch, and T-E fistula without oesophageal atresia (H-type fistula) are presented. These anomalies can be characterised by a failure in separation of the oesophagus and trachea and by atresia of either organ. All of the patients were diagnosed roentgenographically. Since the incidence of associated abnormalities is high in babies with these anomalies, a generalised embryological defect must be a basic assumption in any theory to explain the development of T-E anomalies.


Comparison of the cardiovascular toxicity of three tricyclic antidepressant drugs: imipramine, amitriptyline, and doxepin. Experiments were conducted on puppies to compare the cardiovascular toxicity of imipramine, amitriptyline, and doxepin. The drugs were infused at weekly intervals to produce arrhythmias and/or hypotension. Imipramine was less arrhythmogenic and caused less fall in blood pressure for a given dose than amitriptyline or doxepin.


An unusual case of carbamazepine poisoning with a near-fatal relapse after two days. A severe case of carbamazepine is described in which the drug and its major metabolite were monitored by means of HPLC. After 2 days of treatment a dramatic rise in plasma concentration of carbamazepine and its metabolite was observed, accompanied by a relapse into deep coma, then followed by a rapid elimination of the drugs and complete recovery within 4 days. The possible mechanisms underlying these phenomena and potential therapeutic measures are discussed.


Cancer in a community subject to air pollution by solvent vapors. In an area where the residents were chronically exposed to a mixture of solvent vapors in the atmosphere, the incidence of malignancy is abnormal. Particularly notable is the number of malignant lymphomas [1].


Abuse and pulmonary complications of injecting pentazocine and tripelennamine tablets. A current practice among drug abusers in certain Midwestern and Eastern cities is the intravenous injection of aqueous mixtures prepared from tablets of pentazocine and tripelennamine. Patients present with acute hypoxic episodes and symptoms suggesting physical dependence to pentazocine. Two cases are presented illustrating acute respiratory distress with hypoxia. Available evidence indicates that the respiratory syndrome is produced by talc from the injected tablets. Respiratory support and short-term oxygen therapy have been effective in managing this syndrome. Approaches to the treatment of pentazocine dependence and the role of the antihistamine in potentiating the narcotic activity are also discussed. Physicians, drug abuse counselors, and others should be aware of the abuse potential and pulmonary damage which can result from the intravenous use of this drug combination.


Infections of wounds and soft tissues.

Infections of wounds and soft tissues. Reduction of bacterial dose and support of host defense mechanisms are paramount in the prevention of infections. When infection is established, aggressive search for its cause and extent is necessary. Vigorous nonoperative (antibiotic, nutritional) and operative therapies are needed to eradicate infection and to salvage life and limb.


Postoperative abdominal infections.

Postoperative abdominal infections. Infectious complications remain an important source of postoperative morbidity and mortality. The prevention, diagnosis, and treatment of these problems can be extremely taxing, and skillful clinical judgment and surgery can frequently make the difference between survival or death.


Dissolution of cobalt from hard metal alloys by cutting fluids. On grinding hard metal alloys containing cobalt, the dissolution of cobalt during 5 days was studied for nine commercial cutting fluids. After 1 day, a major part of the cobalt liberated from the material ground is found in solution. This percentage decreases when grinding is continued using the same coolant fluid. Only a small fraction of the cobalt is found in particles in the circulating fluid. The bulk must be in the sediment in the storage tank, where it does no harm to the workers' skin. The final concentration of cobalt found in some fluids may be hazardous.


Allergenic nature of Parthenium hysterophorus. Parthenin has been reported as the active allergen in Parthenium hysterophorus contact sensitivity. A study was carried out to test various chemical fractions of the plant for isolating and identifying the exact allergens. Two additional sesquiterpene lactones apart from parthenin have been shown to be allergenically active. Structures of these sesquiterpenoids are presented. Photopatch tests do not indicate a photosensitizing capacity for these compounds.


Allergy to lanolin.

Allergy to lanolin. The purpose of the present study was to compare the frequency of lanolin allergy during two periods and to assess the adequacy of testing with one standard allergen. Among 1230 consecutive patients with eczema who were standard patch tested, 33 (2.7%), 21 females and 12 males, gave a positive reaction to wool alcohols. Among 899 consecutive patients with eczema standard patch testd and also tested with the lanolin derivatives hydrogenated lanolin 30% in soft yellow paraffin, Amerchol L 101, and a mixture of lanolin derivatives, 60 patients (6.6%), 48 females and 12 males, gave a positive reaction to lanolin and/or its derivatives. The results show that testing with one standard lanolin allergen is inadequate for detecting lanolin allergy.


Nickel dermatitis provoked by buttons in blue jeans. A total of 79 nickel-sensitive patients (65 women, 14 men) were examined with regard to a present or past eczema corresponding to contact with metallic buttons in blue jeans; 63% of the women and 64% of the men had or had had eczema of this kind. Among 40% of the women below 30 years this was the primary site of manifestation. The seriousness of this sensitivity is illustrated by the fact that two-thirds of the nickel sensitive patients with button dermatitis had or had had eczema of the hands. The conclusion is that blue jean buttons should be made of a material which does not contain nickel, for instance zinc alloys which are presently used for some metallic buttons, or they should be designed in such a way that the button does not directly contact the skin.


Cumulative effect of surfactants on cutaneous horny layers: lysosome labilizing action. In order to analyze the role of various surfactants in the abnormal desquamation process of the epidermis in keratodermia type hand dermatitis, the lysosome labilizing effect of surfactants has been investigated by measuring the release of enzymes from lysosomes in vitro using spectrophotometric and gel chromatographic techniques. It has been found that the labilizing effect of surfactants decreases in the order of cationic, anionic, and nonionic surfactants and varies with its alkyl chain length. The relationship of the labilization and skin roughness inducing effect is also discussed.


Nylon stocking dermatitis. An unusual example. We report herein a woman sensitive to nylon stockings of only brown or tan shade. Her situation is interesting for several reasons: she does not react to paraphenylediamine and she reacts to red and yellow dyes, but not to blue or the finish; however, when finish is applied to dyed blanks (red, yellow, or blue) she reacts vigorously to all three. We suspect the finish reacts with the dyes to either expose or produce an antigen previously not available to the skin.


Irritant and allergic reactions to topically applied Micatin cream. Miconazole nitrate (Micatin cream) is a potent antifungal agent. Few side effects have been reported with topical application. We report on 10 patients who exhibited an intolerance to topical use of this drug. Most of the reactions were irritant in nature but in two instances, an allergic contact dermatitis was observed. Patch tests were positive to the cream base.


Does occupational exposure to glass-fibres increase the general skin reactivity to irritants? A total of 33 workers at a glass-wool factory were tested (patch tests with glass-fibres and chemical irritants, epicutaneous tests with Trafuril and intracutaneous tests with histamine) before starting to work at the factory and then re-tested after at least 4 weeks of exposure to glass-fibres. No statistically significant differences in the intensity of the skin reactions before and after exposure were found. Thus no general increased irritancy of the normal skin was induced by the continuous exposure to glass-fibres.


Contact allergy to lidocaine.

Contact allergy to lidocaine. Two cases of contact allergy to lidocaine are reported. They also reacted to chemically related anesthetics of the amide type: one to bupivacaine, mepivacaine and prilocaine and the other to mepivacaine only. The patients also reacted to the chemically nonrelated cincaine, an anesthetic of the ester type. The lidocaine metabolites o-toluidine and mxylidine gave negative reactions.


Spermatozoa repellent as a contraceptive. Early report by Kopp et al. have demonstrated that p-nitrophenyl-glycerol (PNPG) is an effective antiswarming agent in Proteus and that this inhibition may have been caused by PNPG interfering with the negative chemotaxis mechanism in the organism. With an inverted capillary assay, designed to test the motility response of rat epididymal spermatozoa to various suspending conditions including those exposed to chemical gradient, PNPG was shown in this study to exhibit an inhibitory effect at slightly higher than 10(-5) M. Moreover, this inhibitory effect appears to have stemmed from spermatozoa being repelled by PNPG as indicated by the observation that significantly less spermatozoa swim into a gradient of PNPG. The possibility of using spermatozoa repellents as contraceptives is discussed.


Presence of elevated circulating levels of LH during the pre-menstrual period in some copper IUD users and the possibility of their confusion with hCG. A heterologous radioimmunoassay (RIA) capable of discriminating between LH and hCG was used to measure LH levels in sera obtained during the pre- and post-menstrual periods from 80 women bearing copper intrauterine contraceptive devices (IUD). hCG levels in these samples were also estimated by use of a homologous beta-hCG radioimmunoassay and a radioligand-receptor assay. Only two IUD users during the pre-menstrual period had detectable, but low hCG levels. However, LH levels, as estimated by specific RIA, in the serum of these two women were elevated to a level that would cause detection at low levels in the hCG assays. The data thus provide direct evidence to indicate that the positive hCG levels observed by others during the pre-menstrual period in some copper IUD users could be due to the interference in hCG assays by elevated LH.


Effects of RMI 12,936 on some reproductive processes in the female golden hamster. A single subcutaneous injection of 2 mg RMI 12,936 (17 beta-hydroxy-7 alpha-methylandrost-5-en-3-one) given a day after estrus disrupted estrous cycle for over 30 days and inhibited ovulation in 100 percent of treated Golden hamsters. Administration of RMI 12,936 (2 mg) on Day 6 of pregnancy caused termination of pregnancy within 4 days of treatment. In association with the termination of pregnancy was a significant reduction in the concentrations of progesterone and estradiol-17 beta together with an elevated testosterone level. After termination of pregnancy by RMI 12,936, the hamsters remained sexually receptive for 4 weeks but failed to conceive. It is concluded that RMI 12,936 causes termination of pregnancy due to an induction of functional luteolysis.


Endometrial estradiol-17 beta-dehydrogenase activity in women wearing Cu-IUD. In order to determine whether inhibition of the endometrial estradiol-17 beta-dehydrogenase activity by Cu++ could be one of the factors accounting for the enhanced contraceptive efficacy of copper intrauterine devices (Cu-IUD), the activity of the enzyme was measured in endometrial biopsies from women wearing this device. The levels of enzymatic activity found in these specimens were within the range of controls (women without IUD), e.g. 0.1--0.8 and 7--27 nmol E1 formed/mg protein/h in the follicular and luteal phases of the menstrual cycle, respectively. It is concluded that Cu-IUD does not modify significantly either the activity of endometrial-17 beta-dehydrogenase, an enzyme known to regulate the tissular concentration of estradiol, or its response to the inductive effect of progesterone.


Use and acceptance of the "paper pill". A novel approach to oral contraception. A randomized, crossover study comparing the acceptance of and attitudes towards two dosage forms of the same oral contraceptive product - a paper presentation and the conventional tablet, was carried out in a network of rural and suburban research centers in the State of Durango, México. The results failed to show any significant advantage (in terms of acceptability or continuation) of the paper formulation. Although two-thirds of the participants indicated a preference for the conventional tablet, there was a high degree of acceptance of the paper formulation among new oral contraceptive acceptors.


An improved assay for measuring the antimotility activity of chemical agents towards spermatozoa. An assay which allows relatively precise determination of the minimum concentration of test compound required to completely immobilize sperm is described. The use of rectangular cross-section capillaries to contain diluted semen allows facile direct comparison of many individual systems under well-controlled conditions. As a result, simultaneous determination of activity in both saline and serum media is feasible. Using this assay, abrupt loss of motility is observed between adjacent cepillaries differing in test compound concentration by as small a factor as 2 1/3 (1.260).