Ossicular chain reconstruction.

This study represents a review of 121 patients who underwent ossicular chain reconstruction during a five-year period. They depict a general cross section of the sequelae of chronic otitis media. There was no selection of "favorable" cases. Ninety have been followed for one year or more. Hearing results in the most favorable cases (malleus handle and stapes arch present), were improved by the employment of a sculptured, fitted incus prosthesis between the handle and capitulum. Postoperative hearing was improved to within 10 db of the postoperative bone level in about half of the cases. Hearing was 20 db or better in more than 80 percent.


The use of tragal cartilage in ossicular reconstruction.

Readily available tragal cartilage has been found to be a very beneficial autogenous graft source for construction of prostheses to correct those defects in the ossicular chain that frequently occur when the incudostapedial joint is destroyed by middle ear pathology, particularly by the retraction of the posterior, superior quadrant of the tympanic membrane against and/or around the incudostapedial connection. This is true whether there be only erosion of the incus just at the joint, or whether there is erosion of the entire long process of the incus together with the superstructure of the stapes. The various types of deformity and the particular tragal cartilage prosthesis tailored for each deformity, and designed for maximum gain in hearing, are presented together with representative pre- and postoperative audiograms for the variety of types.


Stapes fixation in chronic middle ear disease.

Rigid stapes fixation is not uncommonly found in chronic otitis media and can be caused by several conditions. Careful stapedectomy with some form of ossicular chain reconstruction is the treatment of choice, usually as a second stage procedure. Hearing results to date have been gratifying.


Ossicular reconstruction in tympanoplasty - mobile stapes without crural arches, fixed stapes with and without crural arches.

A description of ossicular reconstruction in problems with the stapes using autograft and/or homograft ossicles is given. The inverted stapes is employed for otosclerosis and tympanosclerosis. The two ossicle reconstruction is used in cases of a mobile footplate with absent crural arches. The reshaped incus is repositioned between the malleus handle and oval window when the stapes is fixed and there also exists a lateral ossicular chain defect. Loose connective tissue is an effective seal for the oval window and is a means of stabilizing ossicular functions.


Plastipore total ossicular replacement prosthesis.

In those ears in which the incus and/or malleus are missing or not suitable, a columella made of high density polyethylene sponge has proven to be very effective. Tissue readily grows into the large pores of this material so that it is well tolerated in the body. During the last six months 54 have been implanted with no rejection so far and a good hearing gain in 43 or 80 percent.


Triple ossicular fixation.

A technique for overcoming conductive deafness secondary to fixation of all three ossicles is described in detail. This procedure is also applicable to previously fenestrated ears.


Symposium: Congenital anomalies of the middle ear. I. Epitympanic fixation of incus and malleus.

Epitympanic fixation of the incus and malleus may be surgically corrected by transcanal atticotomy and removal of the fixed incudomalleolar mass. Restoration of serviceable hearing has resulted in five of six cases by repositioning the natural incus or using a homograft incus.


Symposium: Congenital anomalies of the middle ear. II. Vascular anomalies of the middle ear.

Of all the abnormal situations that one encounters in performing a tympanotomy, probably the last one to be thought of is vascular anomalies, and yet, potentially, this is one of the most hazardous of anomalous problems with which we have to deal. Most of the anomalies which have been reported concern the persistent stapedial artery. This artery arises from the stump of the second aortic arch (stapedio-hyoid artery), it traverses the developing stapes bone, leaving behind a monument to its existence - the obturator foramen of the stapes. The artery exits from the middle ear along the horizontal portion of the facial nerve, traversing this area for a variable distance and then usually divides into an intra-cranial branch and a sphenoidal branch. The stapedial artery in its development before its regression, gives rise to the anlage of many important cranial arteries. These vessels are usually anastomosed with and distributed by the branches of the internal maxillary artery and the ophthalmic artery. The hyoid artery is represented in the adult by the carotico tympanic artery. Anomalies involving the internal carotid artery are much more rare. The anomalies that have thus far been reported are: 1. Absence of the internal carotids. 2. Aneurysms. 3. Unusual courses. Venous anomalies are generally uncommon and are usually represented by an abnormally placed jugular bulb which can simulate a glomus jugulari tumor.


Symposium: Congenital anomalies of the middle ear. III. Congenital anomalies of the middle ear.

Congenital anomalies of the middle ear have been considered rare. The tremendous volume of middle ear surgery performed during the last 15 years has brought attention to numerous anomalies of the facial nerve, ossicles, and middle ear cleft, suggesting that middle ear anomalies are not as rare as once believed. This paper discusses anomalies of the descending and horizontal facial nerve which have been previously reported. The literature of anomalies of the ossicles is reviewed. A very rare anomaly of the carotid artery presenting in the middle ear is described and its surgical treatment outlined. Two anomalies of the middle ear associated with other branchial arch anomalies are reported and their treatment results discussed.


Symposium: Congenital anomalies of the middle ear. IV. Management of profuse perilymph leak.

Profuse perilymph leak during an otological operation can be controlled by inserting an epidural teflon cannula into the lumbar subarachnoid space and draining away the excess spinal fluid. After about 100 cc is removed the perilymph leak stops, and the oval window can be sealed with a living seal, such as vein, and the operation completed. The catheter is left in the subarachnoid space for about four days, with a bottle on the distal end positioned to remove no more than 150 cc of spinal fluid per day. Results with two patients in which this maneuver was used to control profuse perilymph leak are reported.


Facial nerve grafting.

The extratemporal part of the facial nerve and its primary branches may be successfully reconstructed with a suitable nerve graft obtained from the upper cervical region. Special attention to meticulous suturing of the nerve graft to the main trunk of the facial nerve and the branches to the eye and lips should result in satisfactory restoration of facial function in most patients.


Ototoxicity of tobramycin sulfate.

Fifty-four healthy guinea pigs were studied histologically for evaluation of Tobramycin sulfate ototoxicity. They were treated with 50, 100, 150 and 200 mg/kg/day under different schedules. Loss of hair cells occurred when dosage of 1,200 mg/kg was reached. Animals receiving 700 mg/kg were without damage to the inner ear. Outer hair cell loss occurred first in the basal turn, spreading upward. Inner hair cell loss began in the apical turn, progressing downward. When a total dose of 1,400 mg/kg was reached by (two) different schedules the higher daily dose produced about twice the hair cell loss; therefore, the ototoxic effect depends on the total dose but even more on the increased blood concentration.


Traumatic esophagopericardial fistula.

The pathological state of esophagopericardial fistula is a rare phenomenon. Its etiology may be either traumatic or disease induced. In either event, it is a most serious condition with a frequently fatal outcome. This case report concerns itself with an iatrogenic induced esophagopericardial fistula which was successfully treated by a thoracotomy and pericardotomy.


The effect on perilymph of the alteration of serum glucose or calcium concentration.

In the experimentally-induced hyper- or hypoglycemic state, perilymph glucose concentration paralleled the blood concentration, although a delay of about one hour was observed between the time of maximum concentration of glucose in perilymph and its concentration in blood. In hypercalcemia, perilymph calcium concentration steadily increased over a three-hour period, although blood calcium concentration fluctuated during this time. After an initial increase in the CSF calcium concentration, there were insignificant changes during the second and third hours. In animals with thyrocalcitonin-induced hypocalcemia, although blood calcium concentration steadily decreased, its concentration in perilymph and CSF remained practically constant. The present findings suggest that the chemical composition of perilymph can be altered by changing the blood concentration of glucose or calcium. The marked difference of behavior noted between glucose and calcium in these experiments would indicate the existence of different mechanisms for maintaining the homeostatic state for these two substances.


Prosthetic rehabilitation of large midfacial defects.

Advanced tumors of the midfacial region often require removal of the nose, upper lip, portions of the maxilla, and other adjacent structures. When the resultant defects do not lend themselves to surgical reconstruction, prosthetic appliances may be used successfully to restore the functions of speech and swallowing to near-normal levels. The degree of success depends upon the nature of the previous treatment, the existing surgical defect, and the adaptability of the patient. The most important anatomical consideration is the form and amount of the remaining maxilla. Recent advances in the development of the polyurethanes have resulted in lighter, more flexible, and, therefore, better tolerated prostheses. Close cooperation between the surgeon and the prosthodontist is necessary if successful rehabilitation of these patients is to be achieved.


Lymphangiomatous macroglossia.

Lymphangiomatous macroglossia, or giant tongue, usually presents within the first two years of life. The tongue enlarges to the point of protrusion from the mouth with resultant ulceration and frank necrosis of the tip. There may be associated malocclusion and prognathia produced by the enlargement of the tongue. The pathology and clinical manifestations of lymphangioma of the tongue are discussed in this paper, and a case report is presented.


Dermatologic therapy with immunosuppressive agents.

The use of powerful immunosuppressive agents such as methotrexate, cyclophosphamide, and azathioprine in the treatment of serious skin diseases is a relatively recent development whose efficacy is borne out in many studies. Using an immunosuppressant often makes possible an appreciable reduction in dosage of steroid necessary to control disease and, in turn, a reduction in incidence of serious side effects of protracted steroid therapy.


Ill patient with unknown or hidden pregnancy.

Many pregnancies are inadvertently interrupted because diagnostic and therapeutic procedures that are potentially teratogenic are unwittingly instituted. To prevent this ever-present possibility, it is essential that the family physician as well as the hospital's admitting physician know for certain whether a patient in her childbearing years is pregnant. The simple direct question "Are you pregnant?" unfortunately does not always elicit a reliable answer. The patient may not know that she is pregnant, a common occurrence in early pregnancy, or for any of a number of reasons she may choose to conceal her pregnancy. A pregnancy test thus becomes an important diagnostic tool in the armamentarium of every conscientious physician. It should be given routinely to all women of childbearing age before instituting extensive diagnostic x-ray studies, radiation therapy, or chemotherapy that may be contraindicated in pregnancy. Because most contraindicated procedures are performed in a hospital, it is suggested that a pregnancy test on urine be made mandatory on a woman's admission to a hospital.


Genital infection with type 2 herpes simplex virus. A common venereal disease.

Current evidence leaves little doubt that genital herpes is primarily a venereal disease. Like gonorrhea, it is frequently subclinical or asymptomatic. A high rate of infection is found among patients attending venereal disease clinics and among persons of low socioeconomic status. The infection (primary or recurrent) is generally self-limiting, but in a pregnant woman it poses a significant risk to the fetus. It also has been linked to an increased risk of cervical cancer. The Papanicolaou smear is a useful tool for early detection. Effective antiviral therapy for genital herpes is unavailable. Photodynamic inactivation appears promising in recurrent herpes but may be hazardous; malignant transformation of infected cells subjected to this process has been demonstrated in vitro.


Transpubic urethroplasty.

Eleven patients underwent transpubic repair of membranous urethral strictures. Excision of the wedge of pubic bone was not associated with orthopedic disability and provided excellent exposure for primary anastomosis of the urethra. Distal urethral mobilization and incision of the intercrural septum provided adequate urethral length for tension-free anastomosis. Satisfactory results were achieved in all patients, without adversely affecting continence or potency.


Analysis of the treatment of basilar skull fractures with and without antibiotics.

The efficacy of chemoprophylaxis in the treatment of basilar skull fractures was studied in 129 patients over a 2-year period; antibiotics were found ineffective in preventing central nervous system infections, and in some cases may have proved harmful. It is suggested that a more rational approach to the treatment of basilar skull fractures includes close observation of the patient for early signs of meningitis, and if these should develop, treatment with antibiotics appropriate to the organism involved.


Methods of destroying house dust pyroglyphid mites.

Attempts to reduce the growth of house dust pyroglyphid mites by vacuum cleaning, and modifications of temperature and humidity are useful but not sufficient. Their absence in dust from hospital beds which are disinfected led the authors to test PARAGERM AK, a non toxic bactericidal and fungicidal spray. This proved highly effective as an acaricide, killing off cultures of Dermatophagoides spp. and other mites with acceptable and easily produced concentrations, thus providing a new way of combating the house dust allergy mite.


A detailed investigation of circulating IgE levels in a normal population.

Total circulating IgE levels were measured in a carefully selected normal population, using a highly sensitive double antibody assay. The mean level of 36.3 u/ml found in this group is much lower than that reported in all previous studies. No circadian rhythm was evident, but IgE levels varied slightly from day-to-day. IgE levels in 100 serum samples were compared using the double antibody assay and the Phadebas test kit, based on a solid phase technique. A poor correlation was obtained with values below 100 u/ml, however, there was an excellent correlation for samples with IgE levels above this figure.


Secretory and humoral immunologic response of atopic and non-atopic individuals to intranasally administered antigen.

Groups of twelve asymptomatic atopic and fourteen non-atopic individuals were immunized with tetanus toxoid 7.5 Lf units X 2 by means of nasal droplets. Serum and nasal secretion samples were collected on days 1, 15 and 36. Protein content of dialysed secretions was determined by the Lowry method and 1.0 mg/ml samples used for specific antibody assays by passive haemagglutination (PHA) and radioimmunosorption (RISA) employing cyanogen bromide activated Sephadex G-25. IgG, IgA, IgM, and IgD were quantitated by single radial diffusion (SRD), and IgE by the RISA technique. Mean PHA secretion titres rose significantly in both groups during the course of the study. Serum and nasal secretion RISA IgA anti-toxoid levels were higher in the non-atopic group throughout the course of immunization but both groups showed a significant increase in mean levels following immunization (P less than 0.05). Conversely nasal secretion IgE-anti-toxoid levels were significantly higher in the atopic group throughout the course of immunization although no quantitative increase in levels was noted. Total IgG, IgD, IgE, and IgM levels in serum and secretions did not rise during the course of immunization but nasal wash IgA levels rose in both groups. IgD levels were significantly higher in serum and nasal secretions of the atopic group. Our results suggest that atopic and non-atopic individuals differ quantitatively in Ig class specific antibody production following topical mucous membrane immunization.


Mites and house dust allergy. IV. Antigen and allergen(s) of Dermatophagoides pteronyssinus extract.

The antigenic composition of D. pteronyssinus extract was investigated by using antisera raised in rabbits by injection of the mite extract in Freund's adjuvant. Immunodiffusion analysis revealed the presence in the mite extract of many antigenic constituents, most of which were also common to human dander and house dust extracts. Four antigenic components not shared by human dander appeared to be common to D. farinae extract. D. pteronyssinus extract was then fractionated on Sephadex G-75 and DEAE-Sephadex. Immunodiffusion analysis of the most active fraction revealed, after heat-treatment, the presence of three precipitin lines, one of which appeared not to be shared by nutrient medium or by D. farinae extract constituents. When the anti-mite rabbit serum was fixed to an immunosorbent and incubated with a house dust extract it was constantly able to induce a strong decrease or a complete loss of the allergenicity of the dust extract in man. These results suggest that mite allergen(s) are immunogenic in the rabbit and provide more direct evidence for identity of the allergens in house dust and mite.


Ragweed hay fever: treatment by local passive administration of IgG antibody.

To determine whether the local administration of IgG antibodies might reduce the symptoms of ragweed hay fever, we tested the effect of this treatment in fourteen patients in a double-blind pilot trial. The patients were randomly divided into two groups, treatment and placebo, and their symptoms and medication usage were determined during the ragweed pollination season. One group used a nasal spray consisting of phosphate-buffered saline (PBS) containing human serum albumin, whereas the other used PBS containing purified IgG from a subject with a high titre of IgG antibody to partially purified ragweed antigen E. Treated and control groups used comparable quantities of nasal spray, and neither noted any ill effects. Comparison of individual symptoms of hay fever, medication usage, and total symptom scores showed no significant differences between the groups except a lessening of eye symptoms (P less than 0.05) in the treated group. The results suggest that nasal administration of IgG antibody up to five times daily does not alter the severity of symptoms in ragweed hay fever. Furthermore, total serum IgE protein and specific IgE levels increased comparably in both groups, suggesting that passive administration of IgG antibody does not suppress the production of IgE antibody during the pollination season.


Half-life of C1INH in hereditary angioneurotic oedema (HAE).

The half-life of 125I labelled C1INH was determined in patients with HAE and normal controls. There was no significant difference between these two groups. The half-life in the HAE patients was 67.7 hr +/- 4.9 hr (s.d.) and in the normals 64 hr +/- 1.4 hr (s.d.). This finding is consistent with a defect in synthesis as an explanation of the low serum C1INH levels in HAE patients.


Appearance of basophils in the sputum of patients with bronchial asthma.

A total of 108 samples of sputum obtained from twenty patients with bronchial asthma were examined for appearance of basophils and eosinophils. Both cell types are present in sputum during an asthmatic attack and disappear at the conclusion of the attack. Their presence correlates with the severity of the disease. It has previously been demonstrated that the blood basophils count falls during attacks of bronchial asthma, and the present study suggests that basophils move from the blood stream into bronchial tissue during the acute phase of an asthmatic attack.


Asthma due to inhaled chemical agents--the macrolide antibiotic Spiramycin.

One year after starting work in the pharmaceutical industry a 35-year-old non-atopic maintenance engineer developed attacks of sneezing, coughing and breathlessness. These occurred at home during the evening and early morning, never at work during the day. His employment involved contact with a wide variety of chemical agents including the macrolide antibiotic spiramycin. Inhalation challenge tests carried out in hospital with gradually increasing quantities of spiramycin reproduced his symptoms and led to the development of late asthmatic reactions, during which the FEV1 fell by 25% and the FEV1/FVC ratio by 15%. No change occurred in the single breath CO transfer factor nor were crepitations heard over the lung fields which remained normal on chest X-ray. The patient showed positive immediate skin prick tests to spiramycin and developed blood eosinophilia during the late asthma attacks. Inhalation of sodium cromoglycate either before, or before and hourly after the provocation challenge for 6 hr, failed to prevent the late asthma, although its onset was further delayed. On leaving the pharmaceutical industry the patient's symptoms improved but did not finally clear until his wife, who had worked in a clerical capacity in the same factory also ceased her employment.


In vitro diagnosis of atopic allergy. The occurrence and clustering of positive RAST results as a function of age and total IgE concentration.

Specific IgE antibodies were determined on a routine basis in patient sera using the radioallergosorbent test (RAST) with a panel of ten common allergens. Total IgE was also assayed. Of all positive RAST reactions observed, 74% were against the following allergens: horse and cat epithelium, birch and timothy pollen, and house dust. Clustering (occurrence together with significantly elevated frequencies) accompanied both positive reactions to some animal danders and food allergens. Children in all age groups had significantly more positive food RAST results than adults, and this explains the clustering among food allergen results. Children aged 0-4 years had few positive pollen results. Among those with at least one positive RAST result, the mean number of positive results was 3.3, a figure which did not vary with age. In the present patient population 37% had a total IgE above the upper reference (normal) limit, and of these 95% had at least one positive RAST result. A normal or low IgE value was found to be less informative.


Seasonal asthma and the house-dust mite in tropical Africa.

The relationship between seasonal asthma and sensitivity to the house-dust mite has been investigated in a country with large seasonal variations in relative humidity. Of seventy-eight African asthmatics, 64.1% gave a history probably suggestive of sensitivity to house-dust, and 55.1% a history strongly suggestive of such sensitivity. On skin testing, 35.9% had strong reactions to the house-dust mite Dermatophagoides pteronyssinus, compared with 1.9% of fifty-one matched controls without symptoms of chest disease. Few had either a history or skin tests suggestive of pollen or mould sensitivity. Most of the asthmatics were worse during the hot, wet season when the humidity is highest. This is also the time when in-patient asthmatics are most numerous. D. pteronyssinus grows well in warm, damp conditions and it is suggested that sensitivity to this mite may play a significant role in the marked seasonal changes seen in our asthmatic patients.


Betamethasone valerate in the treatment of summer hay fever.

Betamethasone valerate nasal aerosol in a daily dose of 400 micrograms was compared with a placebo in a double-blind trial involving 103 patients with summer hay fever. The patients' and physicians' preference for the active compound was statistically significant (P less than 0.001), with 88% of the patients receiving betamethasone valerate obtaining substantial relief of symptoms. The analysis of patients' daily symptom scores showed that nasal symptoms were significantly reduced by the active aerosol (P less than 0.001). A day-by-day comparison of nasal symptom scores with pollen counts indicated a decreasing allergic response as the season progressed; possible reasons for this are discussed. No clinically significant side effects were observed. Short tetracosactrin tests from ten randomly chosen patients on betamethasone valerate showed no abnormality and nasal swabs for Candida culture from a further thirty-two patients were negative. It is concluded that intranasal betamethasone valerate is an effective and safe form of therapy for seasonal rhinitis.


Clinical and immunological studies of beekeepers.

Thirty-four beekeepers were interviewed and their blood assayed for the presence of antibodies reacting with bee venom, bee venom phospholipase A (PLA), and whole bee body extract. Following a bee sting, most beekeepers experienced only minimal local tissue reaction. Their serum contained high levels of total antibodies (primarily IgG) reacting to bee venom and phospholipase A. These antibody titres correlated with the frequency of bee stings. Bee venom and PLA specific IgE antibodies were present in serum of some beekeepers. Beekeepers who had experienced allergic reactions were characterized by low total antibody and high venom specific IgE antibody titres. Bee body IgE antibodies were found in varying degree and did not correlate with levels of venom IgE antibodies. There was no difference in the titres of bee body IgE in the sera of beekeepers with and without systemic reactions. The data suggest that allergic reactions are mediated by venom specific IgE and immunity is at least in part a function of other antibodies, probably primarily IgG.


Immunological features of asthma (Part II). A report to the Research Committee of the British Thoracic and Tuberculosis Association.

A serological comparison was made of two groups of 120 matched asthmatic and healthy subjects, between the ages of 20 and 49 years and matched for age and sex, in terms of serum total levels of IgG, IgM, IgA, IgD and IgE and of specific antibody levels in each immunoglobulin class to five common UK allergens. The relationship of clinical features to the serological tests was also examined in the asthmatic subjects. The following statistically significant findings were shown. The patients had higher levels than the controls of total globulins and of IgG, IgA and IgD but not IgM. In both patients and controls the females had higher IgM levels than the males. The total IgE levels were higher in patients than in the controls and the male patients had higher levels than the female patients. Total IgE levels were also related, to the numbers of first degree relatives with asthma, hay fever and eczema, to the severity of hay fever and to the amount of time off work in the male patients. In those male patients with exercise induced asthma the total IgE levels were lower than in those not showing this reaction. As for the other immunoglobulins, the only significant differences were a higher IgG level in patients with FEV1 or PFR greater than 50% predicted and a higher IgD level in patients with hay fever. Radio-immunodiffusion tests for specific precipitins were positive for Dermatophagoides pteronyssinus in comparable numbers of asthmatics (25.8%) and controls (21.7%). Positive precipitin tests were uncommon in tests with extracts of grass pollen, Aspergillus fumigatus, cat and dog hair in the patients and even less so in the controls. Positive RAST tests for specific IgE antibodies were obtained in patients and controls respectively, against D. pteronyssinus 59% and 11%, grass pollen 37.0 and 12%, and A. fumigatus 6% and 4%. The male patients showed the closest significant relationship of specific IgE to D. pteronyssinus and the history of house dust allergy, positive skin test and nasal test. In the females only the skin and specific IgE tests were related. Both sexes showed a significant association between specific IgE to grass pollen and positive skin tests and nasal tests, but only the males showed an association with the history. The sizes of skin test weal to D. pteronyssinus were related to the levels of specific IgE antibody. No differences were found between the four skin test groups and between the asthmatics and the control subjects in the incidence of bacterial precipitins and auto-antibodies.


Pigeon breeders' disease--a prevalence study and review.

Among fifty-three Salt Lake City, Utah area pigeon fanciers, 21% were found to have the clinical picture of pigeon breeders' disease. This is a much higher frequency than has been observed previously. Abnormal spirometry and increased skin reactivity to pigeon sera were found more often, statistically significantly, in symptomatic than in exposed asymptomatic fanciers. Pigeon breeders' disease is associated with a variety of abnormal findings; skin test, precipitins, pulmonary function changes and radiographic derangements; but unfortunately none of these are diagnostic. Pigeon breeders' disease is best identified by clinical criteria.


RAST, skin and nasal tests and the history in grass pollen allergy.

A comparison of the RAST (Phadebas), skin prick test, nasal test and a history of hay fever was made in 141 subjects, eighty-seven being prick test positive, with three concentrations of extracts of Sweet vernal (Anthoxanthum odoratum), Cocksfoot (Dactylis glomerata), Meadow fescue (Festuca elatior), Rye (Lolium perenne), Timothy (Phleum pratense), Meadow (Poa pratensis). In adequate concentration any of the species extracts would have sufficed for skin tests, with Cocksfoot pollen the most potent. Correlations found were: positive RAST/prick test, 98%; positive prick test/RAST, 89%; positive RAST/nasal test, 75%, and the higher the RAST the closer the correlation and the higher the nasal sensitivity; nasal test positive/RAST negative, 17%; positive history/RAST, 91%; positive history/prick test, 92%.


Extrinsic allergic alveolitis due to rat serum proteins.

In a research assistant with recurrent episodes of extrinsic allergic alveolitis on exposure to rats, typical systemic and pulmonary reactions on inhalation and positive reaction on prick testing were elicited only by tests with rat serum; precipitins were present against rat serum and rat pelt, but not rat fur, and were also present against rat urine, which may contain large amounts of serum protein and which may have been a main source of antigenic exposure.


Ultrastructural studies on rat skin autografts.

The epidermis of rat skin autografts was studied during the first 14 days of the healing period using light and electron microscopy. Patches of necrotic cells were found on the second and third days while the major part of the cells only showed minor changes from normal skin. At the ultrastructural level the last mentioned cells showed changes, comprising wrinkling of nuclear envelope, aggregation of chromatin, irregular and swollen mitochondria, appearance of different types of vacuoles and a reduction in size and number of keratohyalin granules. These changes were most pronounced on the third day after transplantation. After 8 days only minor changes from the normal epidermis were found and after 14 days the epidermis of skin autografts exhibited a complete healing and regeneration.


On the [4-14C]progesterone metabolism of keloid and hypertrophic scar. A preliminary report.

Tissue specimens from keloids (K) and hypertrophic scars (H), as well as from the healthy skin in their vicinity (KS resp. HS) were incubated in a medium containing [4-14C]progesterone. The metabolites were isolated and verified with thin layer chromatography. All investigated tissue types produced as metabolites of progesterone 5 alpha-pregnane-3,20-dione, 5 alpha-pregnane-3 alpha, 20 alpha-diol, as well as probably 3 alpha/beta-hydroxy-5-pregnan-20 one. The diffusion of progesterone from the medium into the tissue was most effective in K, in sharp contrast to H. The ability of the tissue to take up progesterone from the medium was nearly double in HS as compared with KS. HS seems to metabolize progesterone nearly with the same effectivity as K, and those both twice as much as KS. There were also marked differences in the division of metabolites between the tissue and the medium.


Wound healing with adhesive zinc tape. An animal experimental study.

Wound healing was studied in rats given a diet with a subnormal zinc content (10 ppm). It is concluded that wound healing is impaired in the zinc deficient group compared with animals given a zinc-supplemented diet (150 ppm). Local supplementation of zinc with adhesive zinc tape treatment did not return wound healing to normal in the zinc deficient animals. Histological differences were observed between wounds treated with adhesive zinc tape and those treated with a gauze sponge. In particular, a more pronounced giant cell formation was observed in the gauze treated wound. Simultaneously these wounds showed peak activities of the alkaline phosphatases. A reduction of wound contraction was found in tape-treated wounds. A change in macrophage and fibroblast function during local zinc treatment is suggested. Some effects of wound healing on zinc metabolism are discussed.


On the occurrence of cysteinyldopa and dopa in melanocytes and benign nevi cells.

Previous studies have demonstrated a specific cytoplasmic fluorescence in human melanocytes, as well as in pigmented nevi and in malignant melanomas, when the formaldehyde histofluorescence method for visualization of certain catechol and indole derivatives was used. In malignant melanoma two fluorogenic substances, dopa and cysteinyldopa, were found previously. In human melanocytes and benign nevi cells the fluorogenic catechols have so far not been characterized, since chemical analyses are difficult to perform on skin, due to the small amounts of catechols present. However, using split thickness skin quantitative determinations are possible by sensitive fluorometric methods. The chemical analyses of cysteinyldopa showed that in human adult skin most or all was located in the superficial layers. The only specific fluorescence in the thin skin was found in dendritic melanocytes. The findings leave little doubt that cysteinyldopa is stored in melanocytes although the possibility of a concomitant occurrence of other thioethers is not excluded. Nevi and giant nevi were also similarly studied and we found considerable amounts of cysteinyldopa in the nevi. It seems as if the cysteinyldopa is stored in the fluorescent nevi cells. There was no consistent difference in the content of the catechol derivatives between intradermal and compound nevi.


A retrospective study of 304 cases of malignant melanoma in Malmö 1952-71.

In the city of Malmö with about 250 000 inhabitants and only one hospital, all cases of malignant melanoma are referred to the departments of plastic surgery and radiotherapy. Altogether 304 cases were treated between 1952 and 1971 and all patients were accounted for at the follow-up. This figure does not include cases of superficial melanoma, Hutchinsons melanoma or eye melanoma. The incidence of melanoma increased from 3.4 to 8.0 per 100 000 inhabitants during the period. The treatment was the same during the years. The results of the treatment are presented in relation to the stage of disease, surgical procedure used, site of the tumour and sex. The overall 5-year survival rate without recurrence was 62%, while 6% were alive with recurrence. The corresponding figures for stage I cases were 71% and 7%. Total biopsy of the tumour before more radical surgery was not found to have any disadvantage. In view of the good results, we intend to continue the present method of treatment with addition of adjuvant chemotherapy in the "poor risk" groups.


The influence of primary periosteoplasty on maxillary growth and deciduous occlusion in cases of complete unilateral cleft lip and palate. A longitudinal study from infancy to the age of 5.

The influence of infant periosteoplasty upon the growth of the maxilla, its form and size, and the prevalence of malocclusion in the deciduous dentition was investigated. The material consisted of 66 patients with total unilateral clefts of the primary and secondary palate. Thirty-six had periosteoplasty performed in conjunction with cleft-lip and/or palate repair. Thirty patients were operated upon without periosteoplasty and served as controls. Repair of the lip had a notable effect upon the width of the alveolar cleft and palatal cleft, both in the periosteoplasty cases and in the controls, with no certain difference between the groups. Following lip repair, the anterior width of the alveolar arch was slightly reduced. After palatal repair a further reduction was noted in the deciduous dentition, both in the cases treated with periosteoplasty and in the controls, while the posterior width of the palate across the tuberosities increased during growth. In the deciduous dentition, no differences were found in intercanine and intermolar dimensions between the periosteoplasty cases and the controls. Thus, the new bone formed in the cleft area after periosteoplasty does not seem to withstand the contracting forces introduced by palate surgery. An increased length of the buccal alveolar arch on the cleft side, compared with that on the non-cleft side, was found at both the lip repair and the palate repair in the periosteoplasty cases, as well as in the controls. In the deciduous dentition, this difference was negligible. In the deciduous dentition an anterior position of the lateral maxillary segment proved more common in the periosteoplasty cases than in the controls. On the non-cleft side, there was an increased frequency of mesial occlusion and a corresponding decrease of neutral and distal occlusion in the periosteoplasty cases. No increased frequency of anterior crossbite was found even after repeated periosteoplasty, nor was the maxillary dental-arch length unfavourably influenced. Descriptive analysis of occlusion revealed an increase of buccal crossbite in the periosteoplasty cases of a select group of the widest clefts, treated by repeated periosteoplasty. These cases also had the highest total occlusal score according to the numerical classification, while the total occlusal score after one periosteoplasty in patients with less wider clefts was smaller than in the controls. In all patients who had undergone periosteoplasty new bone formed within the alveolar cleft. A good amount of new bone developed in about half the number of cases.(ABSTRACT TRUNCATED AT 400 WORDS)


Submucous cleft palate.

A report is given of 47 patients with submucous cleft palate operated on during the period 1965 to 1974. The average age of the patients when referred for surgery was high (10.8 years). Eleven patients, or nearly one out of four, had tonsillectomy and/or adenoidectomy performed before the correct diagnosis was made. Sixteen of the patients had a history of recurrent middle ear disease, and 18 patients had another congenital anomaly, the most frequent one being a cleft of the primary palate. Nineteen patients were operated upon with a von Langenbeck palatorraphy, and 28 with a von Langenbeck procedure + a superiorly based pharyngeal flap. Three of the patients were operated on twice. The result with regard to velopharyngeal function was recorded as good in 34 cases, fair in 10, and poor in 3 cases. The results were better in patients operated upon under the age of 7 years. The operative procedures now recommended are: A von Langenbeck (or push-back) closure of the palate combined with a levator sling reconstruction and a superiorly based pharyngeal flap. The possibility for an optimal result is best when the operation is performed at an early age, i.e. as soon as a diagnosis of SMCP and velopharyngeal incompetence has been made. For this reason it is important that better information about the symptoms and signs of SMCP is given to doctors, dentists and speech therapists, who refer these patients to the cleft palate clinic.


Mandibular fractures. I. An analysis of their etiology and location in 286 patients.

Case histories were studied of 286 patients treated for mandibular fractures by the Department of Plastic Surgery in conjunction with the Dental Department at Odense University Hospital between 1964 and 1973. 46.5% of the patients were aged 18-30 years; and 73.4% were male. Mandibular fractures associated with mid-face fractures were most frequently caused by traffic accidents (81%). When the mandible alone was fractured traffic accidents accounted for 50%, while assaults were responsible for 20%. Accidents at work only occurred among the men. Of the 487 mandibular fractures the most frequent site was the condylar process (36%) where half of the fractures in women were localized. Assaults most frequently caused fracture of the angle of the mandible; while falls were most frequently responsible for fracture of the condylar process. The fracture distribution in dentulous and edentulous mandibles differed despite the aetiology being the same.


Surgical treatment of hyperhidrosis axillae.

58 patients have been operated on for axillary hyperhidrosis by excision of the skin and subcutaneous tissue. The hyperhidrotic area was determined by application of a crêpe paper in the axilla. Either 60% or 90% of the hyperhidrotic area was excised, using a bat-like pattern. Only after excision of 90% of the hyperhidrotic area acceptable results were achieved. In a series of 22 patients with 90% excision bilaterally 18 had excellent results, three were good, and one was poor. The entire series was without complication. The advantage of this technique is its simplicity, freedom from complication, performance on an out-patient basis, and short convalescent time.


Leprosy wound healing with ordinary adhesive tape. A preliminary report.

The use of adhesive tape as wound treatment in leprosy cases is described and found to be superior to the classical dressing as regards security and facility of application, and for the rapidity and quality of healing. Its use as a "preventive" treatment is stressed. The results of this study seem to justify the following conclusions: The adhesive tape is easy to handle, it heals the leprosy wounds in about half the time necessary for the classical dressing and it costs about 50 times less.


Spontaneous partial regression of malignant melanoma and its first metastasis. Case report.

A case of malignant melanoma with partial regression of the original lesion and its first metastasis is reported. At the time of almost complete disappearance of the primary lesion a lymph node metastasis was removed and it consisted of necrotic tissue containing masses of melanin pigment. There then was a rather rapid progress of the original lesion and of other metastases and the patient died of disseminated metastases of malignant melanoma three years after the operation.


Pediatric arterial injuries.

Forty-three children were treated for peripheral arterial injuries. Single injuries of the radial, ulnar, anterior or posterior tibial arteries with good collateral supply were best treated by ligation. Injuries about the elbow or knee, associated with fractures, carried the highest morbidity. Early arteriography, prompt exploration in doubtful cases, and a high level of expertise are essential for good results in these two areas.


Incidence, predisposing factors and outcome of pharyngocutaneous fistulas complicating head and neck cancer surgery.

A major complication of head and neck cancer surgery following radiation and extensive resection is pharyngocutaneous fistula. A retrospective analysis of 36 fistula patients out of 376 major head and neck procedures between January 1971 and July 1973 revealed certain guidelines for improved clinical management. Since a large discrepancy existed in the incidence of fistulas between the different surgical procedures, each operative group was examined separately. The incidence, predisposing factors, and methods of treatment for this complication following composite jaw-neck resections and various laryngeal procedures are analyzed and discussed.


Electrophysiologic and electrocardiographic consequences of congestive heart failure.

In order to determine the effect of altered autonomic tone in patients with reduced left ventricular function and congestive failure on atrioventricular conduction, the refractory periods of the A-V conducting system were compared in forty-five patients with normal left ventricular function and fifteen patients with a left ventricular end-diastolic pressure greater than 12 mmHg and a left ventricular ejection fraction less than 50% with symptoms of congestive failure. All patients in the study had resting heart rates of 90 beats per minute or less. Patients with congestive failure were found to have a significant reduction in the functional refractory period of the A-V node (390 +/- 29 msec versus 430 +/- 38 msec; P less than 0.01) and the effective refractory period of the total A-V conducting system (275 +/- 34 msec versus 311 +/- 45 msec; P less than 0.01). In addition, patients with congestive failure had a higher incidence of aberrant conduction of premature atrial contractions (14 of 15 versus 22 of 45; P less than 0.01) and a significantly higher incidence of left bundle branch aberration (50% versus 20%; P less than 0.01). The results indicate significant facilitation of A-V nodal conduction in patients with congestive failure probably due to enhanced sympathetic activity and decreased parasympathetic inhibition. These findings may increase the ability of the clinician to understand electrophysiologic changes in congestive heart failure.


Raynaud's phenomenon in hypothyroidism.

Two patients with Raynaud's phenomenon were found to be hypothyroid and their symptoms disappeared with thyroid replacement therapy. Vascular reactivity studies in one patient demonstrated decreased vasomotor tone after therapy. Raynaud's phenomenon may be an expression of altered autonomic function in hypothyroidism.


Treatment of varicose veins of the lower limbs with ostial incapacity (standard surgico-medical technique).

The following technique is normally used in our Phlebology Centre for varicose veins with ostial incapacity of the internal saphenous vein: A first stage, consisting of an enlarged crossectomy of the internal saphenous vein, combined with a stripping operation, more often long than short. In a second stage it is essential to follow the course of the varicose condition, which is undertaken by the medical team, using a postoperative sclerosing technique. The advantage of this combined technique is that it produces stable results with a minimum number of incisions, so that the results in the great majority of cases, are very satisfactory from the aesthetic point of view.


Hemodynamic changes in arteriosclerotic vs. non-arteriosclerotic rats during the acute stages of myocardial infarction.

Non-arteriosclerotic (virgin), male and female, Sprague-Dawley rats and arteriosclerotic (breeder), male and female rats were subjected to an acute myocardial infarct when injected with two subcutaneous doses of isoproterenol. Female rats, especially female breeder rats with advanced arteriosclerosis, survived their infarcts in superior fashion to male rats or those with the least severe arterial disease. Animals with severe arteriosclerosis showed the least loss of body weight and greatest increase in heart weight on Day 3 when cardiac necrosis reaches its zenith. Blood pressure and pulse pressure was most seriously reduced in animals with no or early arteriosclerosis only, being best maintained in the animals with the most severe arterial disease. Heart rate was not greatly altered in any of the various groups. Ventricular function, i.e., cardiac output, stroke volume, cardiac index, and left ventricular minute work, was severely impaired in the non-arteriosclerotic animals and in those with the least arterial disease. Total peripheral resistance was also least elevated and myocardial contractile strength (peak flow and max dF/dt) was greatest in female breeders with the most advanced arterial disease. Most intriguing, is the seemingly paradoxical but consistent finding that female breeders which develop the most severe arterial disease are able to best maintain cardiac function during the acute stress of myocardial ischemia.


Vertigo of delayed onset after sudden deafness.

An entity of episodic true vertigo of delayed onset following sudden and profound sensorineural hearing loss is described. Data on 12 patients and three case reports are presented. The latency between sudden deafness and the onset of the vertigo varied from 1 to 68 years. The vestibular symptoms are identical to the vestibular symptoms of Ménière's disease, and there is some evidence that endolymphatic hydrops in the previously deafened ear represents at least part of the labyrinthine pathology. Labyrinthectomy in the deaf ear was curative. Tentatively, this entity is best considered a variant of Ménière's disease.


Correlation of cold pressor response with coronary atherosclerosis and left ventricular performance.

A comparison of cold pressor response with coronary arteriography and left ventriculography was made in 26 consecutive patients having chest pain suggesting coronary heart disease. Patients with normal coronary arteriograms and normal left ventriculograms showed normal cold pressor responses. Patients with coronary atherosclerosis and normal left ventricular performance showed an exaggerated cold pressor response, whereas patients with severe coronary atherosclerosis and poor left ventricular performance did not exhibit an exaggerated cold pressor response. In patients with inferior wall myocardial infarction having dyskinesia or akinesia of the inferior wall, the cold pressor response was not impaired. In contrast, patients with anterior wall myocardial infarction and dyskinesia or akinesia of the anterior wall showed a marked impairment of the left ventricular performance and no exaggeration of the cold pressor response.


Painful leg syndrome (pseudo-phlebitis).

Lower extremity venography is essential to confirm the diagnosis of phlebitis when the clinical situation is not completely typical. 8 patients are presented, 6 of whom had been given prolonged prior anticoagulant therapy for phlebitis and pulmonary embolus. Normal venograms and reassurance led to resolution of symptoms in all cases.


Deep vein thrombosis treated with streptokinase or heparin. A randomized study.

Randomly assigned streptokinase or heparin therapy was studied in 50 patients with deep vein thrombosis of less than 2 weeks' duration. Venography was performed prior to therapy, after 3 days, and after 10 days. Two radiologists who were unaware of the patient's therapy compiled a single average lytic score for each patient at each time interval. Lysis of venous thrombi was significantly greater with streptokinase than with heparin after 3 days, but not after 10 days of treatment. Lytic scores achieved with streptokinase were significantly better than those achieved with heparin therapy (P less than .01) in male patients who were symptomatic for 3 days or less. In females, regardless of the duration of symptoms, thrombolytic results obtained with streptokinase were not significantly different than results obtained with heparin.


Furosemide and plasma renin activity in essential hypertension.

Changes in arterial blood pressure, renal electrolyte excretion, and plasma renin activity in response to repeated doses of furosemide were measured in 12 patients with essential hypertension admitted to the medical service for electrolyte balance studies. Eighty and 120 mg/day furosemide in divided doses for 5 to 10 days produced a prompt increase in renal sodium excretion. Urinary Na/K concentration ratios, which were elevated during peak natriuresis, returned to control levels following the initial diuretic response. In 2 patients with high initial levels of plasma renin activity, arterial blood pressure was not reduced by furosemide, and more potent antihypertensive agents were required to control the blood pressure. In the remaining patients, furosemide produced a significant decrease in systolic and diastolic blood pressure. There was a general upward shift of plasma renin levels in terms of 24-hour renal sodium excretion in those who demonstrated an antihypertensive response to the drug. However, the average increase in plasma renin activity after repeated doses of furosemide was not statistically significant and no correlation was demonstrated between the level of plasma renin activity after furosemide and the blood pressure lowering effect of the drug.


The syndrome of nonejection click-late systolic murmur and mitral valve prolapse. A case report and review of the subject.

The syndrome of nonejection click-late systolic murmur and mitral valve prolapse is reviewed. A patient with this syndrome is reported. Physical findings, important diagnostic studies, and possible complications are discussed.


Gas-forming clostridial mycotic aneurysm of the abdominal aorta. A case report.

Gas-forming mycotic aneurysms are extremely rare. A case is reported in which rupture of a gas-forming mycotic aneurysm of the distal abdominal aorta due to Clostridium paraputrificum occurred in an elderly male with a myeloproliferative disorder and a necrotic carcinoma of the colon.


An unusual case of reno-vascular hypertension with multiple arterial stenosis.

A case of juvenile reno-vascular hypertension is presented. Extensive involvement of aorta and its branches was found. The possible inflammatory or congenital origin of the arterial lesion is discussed.


Thromboangitis obliterans: a clinical study with special emphasis on venous involvement.

Sixty-one cases of thromboangitis obliterans (TAO) were studied during 1969-70. Nearly all were males, smokers, of poor socio-economic status. Average age of presentation was 34.2 years. A majority (64%) presented with claudication pain. About one fifth gave history of migratory thrombophlebitis and venography and histological investigations suggested that sixty per cent had venous involvement. Nearly half the patients had involvement of upper limb vessels. Clinical and arteriographic studies showed femoral-popliteal junction to be the commonest site of block. No evidence of coronary artery disease, cerebral vascular disease, abnormal glucose and lipid metabolism was seen in these patients. Arteriographic findings were unlike atherosclerosis obliterans (ASO). From this study we conclude that thromboangitis obliterans (TAO) is a separate and distinct clinical and pathologic entity and the incidence of venous involvement is very high if venographic investigations are combined with clinical examination.


Exercise testing and portable ECG recording in arrhythmia-prone patients.

To detect transient arrhythmias or conduction disturbances, 200 patients with the symptoms of palpitations, syncope or dizziness, and patients with coronary heart disease, angina pectoris, arrhythmias or conduction disturbances on resting 12-lead electrocardiogram, were studied by submaximal treadmill exercise and portable Holter recording. Thirty-nine patients (19.5%) had arrhythmias on the resting 12-lead ECG, 136 patients (68%) showed arrhythmias either on treadmill or Holter recording or both. Eighty-nine patients (44.5%) showed arrhythmias on exercise, while 123 patients (61.5%) had rhythm or conduction disturbances on Holter recording. Twenty-two patients (11%) had arrhythmias only on treadmill walking, while 68 (34%) had arrhythmias only with the Holter. In six patients different arrhythmias was noted by each method. Although the Holter recording technique affords a higher yield of recording transient arrhythmias than did exercise testing, both methods are useful and complementary in evaluating the ambulatory patients suspected of having rhythm or conduction disturbances.


The rational use of diuretics in the treatment of arterial hypertension.

The development of modern pharmacologic diuretic agents has revolutionized the therapy of arterial hypertension. The diuretics currently available are easily administered orally, are effective in the presence of alkalosis or acidosis, are non-toxic and have a low incidence of side effects which are readily circumvented or treated. Loop diuretics such as furosemide have the capacity to be effective in patients with diminished renal function or clinical situations that have a powerful stimulus to sodium retention. In clinical circumstances when renal potassium loss is to be prevented such as in patients receiving digitalis, the addition of a potassium-sparing diuretic to either a thiazide or furosemide will achieve the clinical goal of providing an effective diuresis while inhibiting potassium excretion. The mechanism of antihypertensive activity of the diuretic agents appears to be the reduction of extracellular fluid volumes and plasma volumes. Hence, the clinical dictum that to be effective as an antihypertensive agent, diuretics should be administered in diuretic doses. Besides being the cornerstone of initial antihypertensive therapy, diuretics also play an important role in antihypertensive therapy of patients with moderate to severe hypertension who are receiving potent antihypertensive drugs of the vasodilator or sympatholytic class of compounds. Indeed, one of the most important steps in the successful therapy of these patients receiving multiple drugs, is the re-assessment of the diuretic agent. The sodium retention and consequent fluid volume expansion associated with the administration of these potent antihypertensive agents may often cause these patients to develop apparent drug resistance since the thiazide diuretics are not potent enough to counteract the powerful stimulus to sodium retention caused by these antihypertensive agents. The re-evaluation of the diuretic agent at this point will usually necessitate the substitution of furosemide for thiazide or the doubling of the dose of the present loop diuretic. A working knowledge of the physiology of urine formation and the sites of action of currently available diuretic agents will enable the clinician to tailor the diuretic agent to the clinical circumstances of an individual patient and allow the clinician to rationally select a diuretic for the treatment of arterial hypertension.


Onset and clinicopathological course in Buerger's disease.

From clinicopathological study, vasculitis of Buerger's disease seemed to start at small branch arteries and veins and progress to the trunk artery with thrombus. Progress of vascular lesions in trunk artery was gradual in general; the pathogenesis was briefly discussed.


Budd-Chiari syndrome due to obstruction of the inferior vena cava. A report of two cases.

Two cases of Budd-Chiari syndrome caused by membranous occlusion of the proximal portion of the inferior vena cava are presented. Both were treated surgically, using the modified technique of Kimura in one case, and a resection with direct vision and extracorporeal circulation in the other. Both patients progressed well. We discuss the etiology and pathogenesis of the syndrome, the diagnostic means that can be used, and the importance of early treatment.


Cardio-auditory syndrome of Jervell and Lange-Nielsen.

An 8-year-old deaf-mute girl experienced syncopal attacks. Past medical history revealed cardiac arrhythmia which had developed following an abdominal surgery for a twisted ovarian cyst. Electrocardiogram showed a Q-Tc interval of 40/100 second. The diagnosis was Jervell and Lange-Nielsen syndrome. Etiology, physiopathology, clinical picture, and management of the disease are discussed.


Exercise testing in young asymptomatic diabetic patients.

The cardiovascular response to submaximal bicycle exercise was studied in a group of 19 asymptomatic diabetic patients aged 18 to 39, including 11 males and 8 females and 18 control subjects (9 males and 9 females, aged 20 to 34 years). The maximum heart rate achieved by the control subjects (group I), 175.9 +/- 8.9 beats/min, was greater than that achieved by the diabetic patients (group II), 159.4 +/- 17.8 beats/min, (P less than 0.01). The work load at which the maximum heart rate was reached was lower in diabetic males, 681 +/- 155.4 kg m/min, than in healthy males, 866.7 +/- 139.9 kg m/min, (P less than 0.02). Although systolic blood pressure elevations were comparable during exercise and the postexercise period, the increase in diastolic blood pressure during exercise in the diabetic patients was greater than in control subjects (P less than 0.001). This difference, however, was only observed in the males and not in the females. The difference in diastolic blood pressure was again noted between the groups in the postexercise period; that of group II was higher than that of group I (P less than 0.01). This was particularly notable in the older diabetics (aged 31 to 40 years). One patient in group II developed ischemic ST segment changes, and 1 subject in each group was found to have J junction depression of 1.0 mm or more. The implications of these findings are discussed in relation to the possible pathophysiology of the diabetic patients.


Antiprogesterone effect and midcycle (periovulatory) contraception.

Based on the sequential changes of hormones in plasma and of progesterone binding sites in the uterus, it is suggested to give once a month, at midcycle (around ovulation), either progesterone itself or a parent compound binding to progesterone receptor. The aim is an antiprogesterone effect occurring presumably through a decrease of receptor functioning ultimately expressed some days later by lack of implantation.


Suppression of lactation by an antiestrogen, tamoxifen.

The efficacy of a new antiestrogen, tamoxifen, in the suppression of lactation was tested in a placebo-controlled double-blind trial in 150 puerperal women. It proved to be very effective in preventing milk secretion and breast engorgement when its administration was commenced within two hours after delivery. No side effects were observed. Two dosage schedules were compared.


Pressure in the hydrocephalic fetal head during the first stage of labor.

Intraamniotic pressure was studied in the 30th week of amenorrhea in relationship with fetal intracranial pressure with open-tip catheters. The fetus had a severe hydrocephalus (echoscopy 16 cm) due to a teratologic malformation of the cerebrum. Clinically nonoperative treatment was indicated. Intracranial pressure (X) was invariably higher than intraamniotic pressure (Y) between contractions: Y = 2.04 + 0.54 X, and during contractions: Y = 5.30 + 0.55 X. There was no definite relationship between intrauterine and intracranial pressure, and the fetal tachogram. A definite relationship was established with the supine position of the patient and decelerations in the fetal tachogram. It is suggested that when fetal cardiac decelerations are seen during the first stage of labor it seems advisable to look for factors such as umbilical cord compression and decrease of materno-placental perfusion rather than fetal head compression.


Maternal malnutrition, low birthweight and related phenomena in man. Physiological and behavioral interactions.

The variables producing lowered birthweight include prematurity, maternal genetic tendencies, low prepregnancy weight, low weight gain during pregnancy, pathologies of pregnancy, multiple births, maternal malnutrition, and intrauterine growth retardation. Reductions in intelligence related to low birthweight are distributed equally among different socioeconomic groups. However, when mental subnormality is used as the criterion of impairment, low socioeconomic status is a better predictor of poor outcome than low birthweight. Even when general intelligence is not impaired, low birthweight children show specific cognitive, perceptual and behavioral signs of organic brain damage. In the absence of frank congenital abnormality, absolute birthweight is a better predictor of impaired intelligence than intrauterine growth retardation. Maternal malnutrition during the period of pregnancy does not influence offspring intelligence. Malnutrition throughout the maternal and offspring lifespan does impair intelligence, especially when surrounding social conditions are counterproductive to its development.


Helping the hypertensive patient to help himself.

The control of blood pressure in patients with hypertension is an important challenge in everyday medical practice. It can do much to reduce complications, but too often we fall short of our therapeutic goals. Much more can be done to help our patients help themselves if physicians, along with their paramedical staffs and their patients, make the effort. The results are gratifying in terms of motivation and successful long-term control of the blood pressure and the risks associated with hypertension. This paper outlines objectives and practical approaches to patient education and self-care of this common medical problem.


Advising parents of severely atypical children.

The family physician is often the primary source of continuing guidance for the parents of autistic, schizophrenic, or brain-damaged children. It is essential to anticipate problems in such areas as use of medication, early education, reactions of siblings, and stresses within the lives of the parents. The family physician can help parents find the resources to cope with the multitude of problems confronting them and their children.


Importance of obstetrics in a comprehensive family practice.

Four family practices in the San Francisco Bay Area, two of which did not include obstetrics and two of which did, were examined with reference to their patient populations and to the number of families for which they provided comprehensive, continuous family care. The groups practicing without obstetrics were found to do acute care primarily and, to a lesser extent, long-term care internal medicine, with very little pediatrics or gynecology. The groups practicing with obstetrics did significantly more minor surgery, gynecology, pediatrics, and psychotherapy. During the six-week study, the group practicing with obstetrics saw five times as many patients who were members of families receiving continuous, comprehensive care from the practice under observation. Psychotherapy done by the group including obstetrics was primarily family therapy; for the other group, individual therapy. If larger studies support these findings, then important implications are suggested for training programs in family practice and for the resident deciding to enter practice.


Obstetrics in family practice: a personal and political perspective.

A heated debate is currently taking place concerning the style, methods and location of future obstetrical and neonatal care. On the one hand, there is a trend toward increasing technology of obstetrical and neonatal care with some professional groups favoring regionalization of these services to large regional centers. On the other hand, there are counterforces to such regionalization including community hospitals, many practicing obstetricians, nurse midwives, the women's liberation movement, the "alternative lifestyle movement," the Leboyer concept of delivery, the family-centered maternity care movement, and the family practice movement. This paper explores these issues and presents important reasons for family-oriented obstetric and neonatal care involving the family physician in community settings readily accessible to patients. The inclusion of obstetrical care as an integral part of family practice is important to the growth and development of the specialty.


An audit of obstetric care in a university family medicine department and an obstetrics-gynecology department.

The care of obstetric patients in a university family medicine department was compared with that in the obstetrics-gynecology department of the same university. The obstetric service patients tended to be at higher risk due to a higher black population (24.2 percent vs 6.3 percent), greater prepregnancy weight (mean 154.0 lbs vs 113.9 lbs), and a greater number of patients referred from the community because of prenatal complications. However, the family medicine patients had a higher incidence of premature rupture of membranes (26 percent vs 11 percent), and were therefore at risk for several complications. Family medicine nulliparas had first stages of labor which lasted an average of 12.2 hours as opposed to obstetric service nulliparas whose first stages averaged only 9.2 hours. There were more family medicine than obstetric service patients who received no anesthesia (18.0 percent vs 10.2 percent). Elective low forceps were used more often by obstetric service physicians than by family physicians (28.2 percent vs 15.3 percent). Mothers on the family medicine service had more puerperal complications than those on the obstetric service (16.0 percent vs 5.6 percent). No serious discrepancies in quality of care could be found between the two services.


In-Training Performance Assessment in family practice.

The In-Training Performance Assessment (ITPA) is an evaluation instrument derived from 174 basic objectives in family medicine. The instrument was applied to two consecutive classes of fourth-year medical undergraduates during the family medicine clerkship. Comparisons were made of two scoring systems: one measuring mastery of the objectives using the criterion of performance expected of a fully qualified family physician, the other using traditional categories of "poor", "satisfactory", "good", and "outstanding". The mastery evaluation model made it more difficult to achieve the objectives but had no effect on the discriminatory ability of the objectives when compared with the traditional evaluation method. The mastery model showed "management" to have the greatest differential between medical students and qualified family physicians. The evaluating supervisor was most influenced by the student's assessment in "problem-solving" using the traditional method, and by "management" using the mastery model. Management skills accounted for 89 percent of the variance of the overall competence assessments.


An in-training examination for residents in family practice.

An in-training examination for family practice residents has been developed and used in a regional network residency program over the past three years. The most striking result has been the strong preference expressed by residents for question-specific feedback in order to facilitate learning after taking the examination. A well-designed in-training examination has the potential to meet both individual resident and program goals as an additional measure of resident performance and growth, as well as of the effectiveness of teaching in the various curricular areas. In-training examinations for residents are in use by 12 other specialties in medicine, and have been well-accepted by program directors and residents. A nationally-sponsored in-training examination for family practice residents is needed which includes maximal teaching capability through comprehensive and specific feedback.


Syncope.

Syncope is usually easily diagnosed, but sometimes it is confused with hypoglycemia, epilepsy, cerebral vascular disease, "drop attacks", hyperventilation attacks, and hysterical faints. Syncope is usually a benign disorder, but sometimes it is a manifestation of a serious neurologic or cardiac disease. This paper provides an approach to the evaluation and management of patients with this disorder.


Management of the multiproblem seductive patient.

A seductive gesture by a patient towards a physician is not uncommon in clinical practice, and presents a variety of problems in maintenance of the doctor-patient relationship and management of the patient's medical problems. Medical, psychological, and social factors must be considered in resolving these problems. This Grand Rounds presents such a case and discusses alternative approaches to patient management and the role of other health professionals in the care of such patients.


Effect of selenium compounds on selenium content, growth and 35S-cystine metabolism of skin fibroblasts from normal and cystinotic individuals.

Kidney samples from children with the inborn metabolic disease cystinosis contain 4 times more selenium (Se) than do kidney samples from normal individuals (p = 0.1). However, when cultured skin fibroblasts from cystinotic patients and normal control individuals are incubated in Se-D,L-methionine, Se-D,L-cystine, Se-cystamine X HCl, Se-urea, selenite or in medium without added selenium, only the cystinotic fibroblasts grown in Se-urea or selenite (SeO3=) contain more selenium than do the corresponding normal cells (p less than 0.05). In both types of cultured fibroblasts, the order of descending toxicity per ppm selenium is: Se-urea greater than Se-cystamine greater than Se-cystine greater than or equal to SeO3= much greater than Se-methionine. High (apparently toxic) concentrations of Se-urea and Se-cystamine lower the elevated intracellular free (nonprotein) cystine content of cystinotic fibroblasts to less than 60% of control values; at lower concentrations, these compounds raise the cystine content of these cells to over 140% of control values. Appropriate concentrations of SeO3=, Se-cystine and Se-methionine also elevate the free cystine content of the cystinotic cells. During a 75 minute incubation in 35S-cystine, the incorporation of 35S into the acid precipitable (protein) fraction of both cell types is significantly inhibited by Se-cystamine (approximately 55% control; p less than 0.05). The incorporation of 35S-cystine into glutathione is inhibited by Se-cystine (approximately 40% control) in both fibroblast types (p less than 0.05). In cystinotic cells, Se-cystamine significantly reduces incorporation of 35S-cystine into the cystine pool (40% control) as does SeO3= (67% control; p less than 0.05). Protein and glutathione synthesis in cystinotic fibroblasts are more strongly inhibited by Se-cystine and SeO3=, respectively, than in normal fibroblasts (p less than 0.05). These studies demonstrate that selenium compounds exhibit a different sequence of toxicity in fibroblasts than in the intact animal and that some previously unreported metabolic effects (i.e. inhibition of glutathione synthesis) may contribute to their toxicity.


Reactions of bis(thiosemicarbazonato) copper(II) complexes with tumor cells and mitochondria.

The respiration of Ehrlich ascites tumor cells is inhibited by 3-ethoxy-2-oxobutyraldehyde bis (thiosemicarbazanato) copper (II). State 3 oxidative phosphorylation in mitochondria from tumor cells is also inhibited, with the effect more pronounced using glutamate or pyruvate-malate as substrates than with succinate. The disruption of oxidative phosphorylation in bovine heart mitochondria is qualitatively similar. The principal site of inhibition is in coupling site one, energetically between the electron transport site chain and the locus of uncoupling by 2,4-dinitrophenol. This appears to contain thiol groups which are oxidized by the complex. For a series of bis (thiosemicarbazonato) copper complexes, the extent of inhibition of heart mitochondrial oxidative phosphorylation is correlated with the reduction potentials of the complexes and with their in vitro cytotoxic effects against Walker 256 carcinoma tumor cells.


Inhibition of the genesis of spontaneous mammary tumors in C3H mice: effects of selenium and of selenium-antagonistic elements and their possible role in human breast cancer.

The inhibitory effect of selenium on the genesis of spontaneous mammary tumors in C3H mice is statistically significant even at toxic levels of selenium (5 and 15 ppm of Se in form of selenite added to the supply water), no evidence for stimulation of tumor growth by selenium has been obtained. Arsenite lowers the tumor incidence at higher dosage (80 ppm of As in supply water) as well, but animals developing tumors under these conditions demonstrate significantly enhanced tumor growth rates. The addition of subtoxic concentrations of zinc (200 ppm in form of ZnCl2) to supply water containing 5 ppm of Se abolishes the cancer-protecting effect of selenium. The latter result is of possible importance with respect to the human breast cancer mortality experience: The calculated dietary zinc intakes of average adults in 28 countries correlate with the female age-corrected mortalities from breast cancer directly, with P less than 0.005. The zinc concentrations in whole blood from donors in different parts of the U.S.A. are also directly correlated with the female breast cancer mortalities.


Radionuclide and angiographic studies of placental circulation in man and rhesus monkey.

Imaging maternal and fetal circulation during perfusion of isolated human placental lobules was performed. Radionuclide and contrast angiograms, specimen scans, and histologic preparations obtained on human material during in vitro investigations were compared to the results obtained in vivo on pregnant rhesus monkeys. The distribution of maternal blood flow within the placenta appeared similar in both human and rhesus studies. The 'spurts' of radiopaque medium shown on the contrast angiograms correlated with the appearance of areas of increased radioactivity. These 'hot spots' are located where the uteroplacental spiral arteries open into the intervillous space or where the perfusion cannulae irrigate the maternal side of the placenta. Time-radioactivity curves reached an early peak and remained the same as did their distribution on delayed scans. The 15 to 30 micron microspheres injected into the intervillous spaces are not removed onto the venous side by maternal flow through arteriovenous communications (or 'shunts') but are retained in localized areas of the intervillous space adjacent to the spiral arteries. Many of these microspheres adhere to the 'brush border' of the chorionic villi syncytiotrophoblast. These comparative studies confirm that rhesus monkeys and perfused human placental lobules are relevant models to investigate uteroplacental hemodynamics.


Evaluation of fetal heart rate in relation to the intrauterine 20 mm Hg level.

The purpose of the author's study was to investigate whether any changes in fetal heart rate (FHR) and in fetal acid-base status could be observed when the intrauterine pressure rises above 20 mm Hg. 16 primigravidae were studied. In 11 out of 16 patients labor was induced by amniotomy, in 9 cases oxytocin was given, and in 12 patients pethidine and promethazine (Phenergan) was administered. Two new parameters were introduced into the study of the collected material: the peak variation in FHR (bpm) i.e. the difference between the highest and lowest FHR over a given period of time; the contraction energy, i.e. the product of duration and intensity of intrauterine contractions as measured from the 20 mm Hg level. In 15 out of 16 women the mean peak variation in FHR was highest during a uterine contraction (greater than 20 mm Hg). After a uterine contraction (less than 20 mm Hg) the mean peak variation did not immediately return to control values. It is suggested that in the 16 patients studied, the increase in FHR peak variation during uterine contraction is basically caused by a slight transient fetal hypoxia, exaggerated during the expulsion period of labor by cord entanglement.


Prevention of postpartum venous thrombosis with low doses of heparin.

Postpartum superficial and deep venous thrombosis were found in 22.3% and 5.3% of women with varicose veins who delivered vaginally, or by cesarean section. The preventive use of low doses of heparin (5,000 U every 12 h injected subcutaneously) in 116 parturients with varicose veins reduced significantly the incidence of postpartum venous thrombosis. None of the 26 women with previous thrombosis who received preventive treatment, developed such an event.


Maternal anticonvulsants and perinatal risk.

According to data found in the literature, children born to epileptic mothers on anticonvulsant therapy have an increased perinatal mortality rate, namely 2-3 times the average. The congenital malformations attributed to anticonvulsant drugs cannot fully account for this high mortality rate. A case is described in which a severe bleeding disorder manifested itself in successive offspring. A discussion follows in which this defect in blood coagulation in the newborn and the role played by vitamin K is considered as representing an important and preventable cause of neonatal death and morbidity. Other features of the postnatal syndrome (CNS depression, congenital heart disease, withdrawal symptoms, anemia) are mentioned in the case report. Suggested preventative measures employing vitamin K, folic acid and vitamin D are briefly discussed.


Parental smoking. Its effects on fetus and child health.

Smoking is a risk factor in pregnancy. Maternal smoking reduces the birthweight by 150-250 g (dose-response relationship), shifting the birthweight (and length) distribution to the left. Reduction of birthweight without shortening of gestation creates a group of small-for-date babies. Intrauterine hypoxia seems responsible for the growth retardation in smokers' babies as in babies of mothers living at high altitudes. Cigarette smoking of the mother affects fetal oxygenation, due to high levels of COHb in the blood of both mother and child. This observation is strongly supported by animal experiments. The total of (abortions), stillbirths, early and late neonatal mortality (especially stillbirths) is higher in babies of smoking than in those of nonsmoking mothers and highest among the poor. Approximately 5% of all stillbirths and neonatal deaths must be attributed to the increased mortality risk for the infant of mothers who smoke during the second half of pregnancy. Pregnancies of smoking mothers show about the same increase in infant wastage as pregnancies at high altitudes. The babies of smoking mothers show little excess of congenital malformations, if any. The placenta coefficient is increased. This symptom of compensatory placental hypertrophy cannot avert some impairment of fetal nutrition. There is less preeclamptic toxemia in smokers than in nonsmokers, but a higher incidence of antepartum hemorrhage and placental separation. Concerning long-term effects, smoking during pregnancy seems to be associated with a slight impairment of mental and physical growth. When the mother is nonsmoker and the father smokes more than ten cigarettes daily, an increase in perinatal mortality seems probable. Smoke aggravates the asthma of children in about two-thirds of those whose parents smoke. Healthy children of smokers are sick more frequently (primarily respiratory illness) than those of nonsmokers. Smoking parents and teachers stimulate their children and pupils to start smoking. Once smokers children may remain smokers. From the polemics on cause (smoking) and association (smoker) regarding the effects of parental smoking on the health of the fetus, the conclusion must be that health workers involved in obstetrics have great responsibilities in the antismoking campaign.


Intermittent low-dose administration of prostaglandins intraamniotically in pathological pregnancies. A comparison with oxytocin and ergometrine.

The effects of prostaglandin F2 alpha on uterine contractility were compared with the effects of oxytocin and ergometrine. All patients had an intrauterine death. 5 patients were induced with prostaglandin F2 alpha, given intraamniotically in low doses, starting with 125 micrograms. Doses were increased in relation to uterine activity. 5 other patients were induced by intravenous administration of oxytocin and ergometrine. Uterine pressure was monitored by a transabdominal open-tip catheter system. Results were quantitated in tonus (mm Hg), amplitude (mm Hg), frequency (number of contractions per 10 min), Montevideo units, active and total pressure areas per 20 min. Possible biochemical and coagulation changes were controlled before, during and after induction. Changes did not occur. Intermittent increasing small doses of PGF2 alpha increased uterine activity exponentially. Hypertonia persisting longer than 5 min was seldom seen with oxytocin or with PGF2 alpha. Ergometrine increased frequency of uterine contractions, without influencing tonus, probably due to a specific effect on the 'archemyometrium'. The induction-delivery interval was shorter in the PGF2 alpha group (range: 6-15 h) than in the oxytocin group (range: 7-24 h). In the latter group more inductions were necessary to complete delivery. Using PGF2 alpha in these small doses did not cause any side effects. With the intraamniotic injections, starting with 125 micrograms PGF2 alpha, clinical results are the same as those reported in the literature for high doses.


Ovarian morphology in oligomenorrhea.

An account is given of the ovarian histology on 38 patients complaining of oligomenorrhea. The majority of these patients, 22, had polycystic ovaries, but in 11 the ovaries were comparatively normal in appearance. In another 3 they were small and inactive. The remaining 2 cases had chromosomal anomalies. The polycystic ovaries could be divided into two groups, one showing little follicular activity, the other a great deal. The maturation of most follicles in all ovaries appeared to be restricted and antral follicles rarely grew beyond a diameter of 4-5 mm. It is suggested that this degree of maturation is related to a low tonic secretion of FSH. An excessive production of luteinized thecal cells was found around most antral follicles. Polycystic change in these ovaries is mainly due to the presence of many atretic follicles. Luteinized thecal cells persist after atresia and it is suggested that this may be the result of a tonic secretion of LH. The lack of preantral and antral follicles in one group of polycystic ovaries may indicate a prolongation of the atretic process. Ovulation occurs with considerable frequency in these women. The mechanism is obscure.


Immature delivery after intrauterine Candida albicans infection.

The case is presented of a patient who delivered an immature infant after an intrauterine candidial infection in the presence of an intrauterine contraceptive device (IUD). 8 other cases of intrauterine Candida infection leading to immature deliveries were gathered from the literature. On the basis of the pathologic findings, the medium of infection is thought to be the amniotic fluid.


An approach to the treatment of hypertension in the aged.

Because of the multiplicity of disease conditions and diminished tolerance for drugs in the aged, it is necessary to know concomitant pathologic conditions to determine which antihypertensive drug to use. In the Philadelphia Geriatric Center, there are about 1,000 residents, between 70 and 100 years of age. About 40% have hypertension; almost 50% have or once had depression; there are many cases of hiatal hernia and/or peptic ulcer; in one subdivision of residents, almost 40% have renal disease with BUN above 30 mg/100 ml. In antihypertensive treatment, some individuals respond fairly well to reassurance and weight reduction, when obese, even without drugs. All are given a low-salt diet. A diuretic is first used--thiazide in cases of good renal function, furosemide with impaired renal function. Liquid potassium supplements are given. If there is but little reduction in blood pressure in several weeks, methyldopa is added in ascending doses, in cases with or without renal impairment. In hypertension with impaired renal function, furosemide and/or methyldopa were especially valuable. Furosemide as an antihypertensive drug was also noted to delay the onset of congestive heart failure. Since reserpine can aggravate peptic ulcer and can precipitate or aggravate depression, it should seldom be used to treat hypertension in the aged. Guanethidine is rarely used, since it can cause cerebrovascular insufficiency and marked weakness. High blood pressure should be reduced slowly in the aged, to avoid untoward effects.


The spectrum of arteriographic findings in Osler-Weber-Rendu disease.

In Osler-Weber-Rendu syndrome, visceral organs are frequently involved in addition to cutaneous and mucous membranous lesions. Detailed arteriographic investigation of 5 patients with this abnormality disclosed characteristic angiodysplastic lesions involving the lungs, liver, spleen, pancreas, gastrointestinal tract and mesentery. Arterial and aortic aneurysms appear to be an integral part of this abnormality. Common to angiodysplastic lesions is a variable degree of arteriovenous shunting. The arteriographic characteristics and the hemodynamic significance of major visceral arteriovenous shunts in hereditary hemorrhagic telangiectasia are discussed.


Treatment of the bradycardia-tachycardia syndrome with permanent demand pacing.

The bradycardia-tachycardia syndrome (paroxysmal supraventricular tachycardia alternating with sinus bradycardia and episodes of sinus node arrest) has previously presented a complicated therapeutic dilemma when excitatory and suppressive drugs have been utilized. A patient with this syndrome successfully treated with a permanent ventricular transvenous demand pacemaker is presented. Various aspects of this syndrome as well as facets of diagnosis and treatment have been reviewed and discussed. Significant underlying cardiac disease was ruled out in this patient by the usual diagnostic methods including left heart catheterization and coronary angiography. An interesting possibility of the relationship of vagal stimulation secondary to hiatus hernia as an etiologic factor in this syndrome has been discussed. The opinion is expressed that the currently preferred method of treatment is the insertion of a permanent transvenous pacemaker alone or in conjunction with antiarrhythmic drugs, preferably digitalis and propranolol.


Renal artery embolectomy.

A patient with rheumatic heart disease developed right renal artery embolism and was treated by renal artery embolectomy. After a brief historical data, etiologic factors, clinicopathologic points, and treatment of the disease have been discussed.


False positive 125I fibrinogen test.

125I fibrinogen test was performed in 20 selected patients who presented with symptoms suggestive of deep venous thrombosis. The incidence of a false positive study was found to be very high: 90%. An increased accumulation of fibrinogen was noted over recent, well-healed surgical incisions, diffuse or focal inflammatory sites, hematoma and also, following a venogram or arthrogram test. The large number of coincidental circumstances that result in an abnormal accumulation of 125I fibrinogen lead us to believe that venogram is the procedure of choice in patients with symptoms simulating thrombophlebitis.


Acute and chronic venous insufficiency in the finger.

Venous hypertension with subsequent chronic venous insufficiency and its sequelae in the hand is reported as an uncommon complication of arteriovenous fistulae for hemodialysis.


The role of metal ions in the activation of arginase.

The role of metal ions as activators of arginase hydrolyzing arginine were studied. The metal ion is assumed to form a complex with arginine and to promote the enzymatic reaction. The activating ability of the metal ion appears to be governed by the chelating ability and/or the coordination numbers which determine whether the metal ion combines with the enzyme or the substrate (or both substrate and enzyme) and factors which influence the configuration of the resulting complexes.


Protein-metal ion interaction: volume effects produced by the interaction of proteins with metal ions.

The interaction of metal cations with single chain globular proteins produces volume increases, the magnitude of which is determined primarily by the ion and to a lesser extent by the protein. The cations are listed in ascending order of volume change: K(I) less than Mg(II) less than Sr(II) less than Ca(II) less than Co(II) less than Ni(II) less than Cd(II) less than Zn(II) less than Cu(II) less than Pb(II). This sequence held for all cation-protein systems investigated except for Cd(II) which produced a slightly larger volume effect than Zn(II) with lysozyme. The volume changes attributed to protein-cation interaction are positive and range from 8 ml/10(5) g of protein for the reaction on 0.05 M KNO3 with bovine plasma albumin to 2320 ml/10(5) g of protein produced by the 0.20 M Pb(NO3)2-myoglobin system. A similar classification scheme was not possible for the proteins. For example, volume increases of 45, 50, 80 and 95 ml/10(5) g of protein were produced when 0.05 M Mg(II) reacted with bovine serum albumin, ovalbumin, sperm whale myoglobin and lysozyme, respectively. However, when 0.2 M Pb(II) was the reactant the values were 1930, 846, 2320, and 1120 ml/10(5) g of protein. Volume effects produced by Cr(III), Al(III) and Fe(III) were determined, but the calculated results are considered dubious because the volume changes are a complicated function of protein-cation and protein-proton interaction.


Malate dehydrogenase and glucose-6-phosphate dehydrogenase activity in livers of Ni-deficient rats.

In experiments using rats it was shown that inadequate dietary supply of Ni reduces growth and lowers the erythrocyte count, hematocrit and hemoglobin level in blood, that the Ni supply affects the trace element content of iron, copper and zinc in various body organs, and that the absorption of iron is greatly impaired by Ni deficiency. For further biochemical criteria on the essentiality of nickel, the activities of two dehydrogenases, malate dehydrogenase and glucose-6-phosphate dehydrogenase, were measured in liver homogenates from two generations of rats at 30 and 50 days of age. In the 30-day-old rats of both the F1 and F2 generation, the activity of the malate dehydrogenase fell to about two-thirds the level of control animals. In the liver of the 50-day-old rats the activity of this enzyme was about the same in deficient animals as in the controls. The activity of glucose-6-phosphate dehydrogenase of Ni-deficient rats was reduced by 85% in the F1 generation and by 56% in the F2 generation at 30 days of age as compared with control levels. In 50-day-old rats the activity had fallen to half the level of control animals at 30 days of age. At the age of 50 days, there was no significant difference between the deficient and the control groups of either generation.


Cobalt(III) complexes of bidentate azotyrosine analogs.

As analogs for cobalt(III) complexes of bidentate azotyrosine in proteins, several cobalt(III) complexes of bidentate azophenols have been prepared and characterized. Tris(2-phenylazo-p-cresolato)cobalt(III) was shown to be a poor model complex for this purpose; while cobalt(III) complexes of either 2-phenylazo-p-cresol or 2-(4-carboxyphenylazo)-4,5-dimethylphenol with the linear tetradentate ligand ethylenediamine-N,N'-diacetic acid are very useful as model complexes. The complexes were characterized by magnetic susceptibility, visible spectra and 1H NMR. In the case of one of the mixed ligand complexes, a detailed description of the stereochemistry was possible. Comparisons of the spectral characteristics of metal complexes with bidentate and tridentate azophenols are made. These model studies are essential to a program involving the site specific modification of proteins with substitution inert metal ions.


Inhibition of L-alanine aminotransferase by lithium salts.

Pharmacologic concentrations of either LiCl, LiN03 and LiF or the lithium salts of pyruvic or glutamic acids inhibit the formation of alanine arising from the transamination of glutamate in the presence of pyruvate. Lithium pyruvate is the most effective inhibitor, while the addition of K+ to the incubation reaction can effectively reduce this inhibition. Some possible modes of action of the lithium ion is presented.


Coordination of biogenic amines with synaptosomal and vesicular metal ions: equilibrium and spectral studies in model systems.

Thermodynamic equilibrium studies using model systems were carried out on the nature and extent of coordination of twelve different biogenic amines and adenosine-5'-triphosphate (ATP) with the bivalent metal ions, viz., Ca2+ and Zn2+, which occur in the subcellular fractions of the brain, at 25.0 +/- 0.1 degrees C and at an ionic strength of 1.0 (KNO3). In the combined presence of the individual monoamines and ATP the metal ions were predominantly coordinated by ATP in the pH range 3.0 to 6.5 with binding constants (log KML) of 2.84 +/- 0.06 and 3.19 +/- 0.39 for the Ca2+ and Zn2+ chelates, respectively. Each of the monoamines coordinated with the metal-ATP chelate above pH 6. The stabilities of the chelates of some of the amines with Ca2+ -ATP (1:1) system were NE, 2.33 +/- 0.33; AA, 2.24 +/- 0.19; OA, 1.94 +/- 0.29; NMeN, 1.60 +/- 0.22; DA, 2.14 +/- 0.09. Values for the Zn2+-ATP-amine systems were: NE, 8.35 +/- 0.26; OA, 4.53 +/- 0.07; DA, 10.05 +/- 0.39. Absorption spectral studies were carried out in order to examine the nature of coordination of NE, DA, TA, and AA with Cu2+, Fe2+, and Mg2+ ions in the combined presence of ATP. Results of the spectral studies taken together with the (thermodynamic) equilibrium data have indicated that in the pH range of biological interest, the catechol amines (NE and DA) and ATP are both coordinated to the "synaptosomal and vesicular" metal ions. The results further indicated that both the pyrocatechol and the ethanolamine groups of NE might be involved in the coordination of Cu2+. However, the interaction of the ethanolamine group of the NE molecule with the rest of the metal ions was not indicated.