An improved septoplasty: the microsurgical suture technique. An improved septoplasty procedure has been performed on 204 patients, 49 in combination with rhinoplasty. There were 2 minor complications: 1 small perforation and 1 septal hematoma. The use of septal sutures avoids the necessity of postoperative intranasal packing or splints. Magnification, proper lighting, and improved instrumentation have simplified the technique, and a nontraumatic anatomical dissection can more easily be performed on the most complicated septal deformities. By dispensing with intranasal packing, a one-stage septorhinoplasty can be done without fear of producing a widened dorsum from outward pressure of the packs. The sutures also increase the stability of the septum by preventing displacement of the caudal portion during the healing process. Postoperative patient discomfort is minimized, as the airway is not blocked by packs; painful removal of the packs is also eliminated.


Cervical lifts: the value of platysma muscle flaps. Patients and physicians who are not satisfied with the results of cervical lift procedures that rely on skin tension alone frequently complain of persistent or recurring neck longitudinal bands; of lack of pleasing concave contours; or of lack of definition of the mandibular border. Platysma muscle bands can be eliminated with long-lasting improvement in the neck contour if the objectionable bands are completely incised and the platysma muscles are transformed into a deep-layer supportive neck sling. The techniques described utlilize platysma muscle flaps to eliminate vertical platysma muscle bands and folds, to achieve pleasing concave neck contours, and to produce definition of the mandibular border.


Muscle repair in unilateral cleft lip, based on findings on electrical stimulation. The appearances, distribution, and direction of muscle in the unilateral cleft lip as indicated by electrical stimulation are described. The findings differ from those reported by Fara and associates in their dissections in that functionally the fibers do not appear to parallel the margin of the cleft. Based on these findings, a method of layer-by-layer, step-by-step closure of the unilateral cleft lip is described that attempts to split the orbicularis bulge and advance the lateral muscle into the philtrum to a position more nearly imitating the direction and extent of the muscle in a normal lip.


Lengthening of the short columella associated with bilateral cleft lip. Operations for lengthening the columella can be classified into three groups on the basis of source of material: lip, nose, or ear. When seen in profile, the middle of the lip provides one-fourth to one-third of the forward projection of the columella as compared with the level of the alar bases. Complete bilateral cleft lips usually benefit from columellar lengthening, but symmetrical, incomplete clefts rarely require it. Ancillary procedures, such as correction of a retruded maxilla by Le Fort I osteotomy or by contour build-up, can enhance the overall result. Our experience with advancement of skin from the floor of the nose and ala [15], skin from the alar margins at the tip [7], prolabial advancement flaps, fork flaps, and composite earlobe grafts is reported.


George David Pollock and the development of skin grafting. George David Pollock, F.R.C.S., convinced the world of the efficacy of skin autografting and homografting. Previous studies on the priority of skin grafting are reviewed. The life of Pollock, including a glimpse of the surgical world of the Victorian era is described. A detailed analysis of the roles and relationships of Pollock, Reverdin, and Gosselin is given.


The world of William L. White: a macro-view. On May 14, 1977, a group of colleagues and former trainees gathered in Pittsburgh to honor Dr. William L. ("Willie") White, Chief of the Section of Plastic Surgery at the University of Pittsburgh School of Medicine, on the occasion of his retirement after 18 years as program director. Participating in the festivities were Drs. Henry H. Bahnson, Robert M. Goldwyn, Salvador Castanares, Victor HayRow, Frederic Rueckert, Richard P. Jobe, Dwight C. Hanna, George S. Richardson, Dennis J. Hurwitz, Garry S. Brody, Ronald J. North, Ross H. Musgrave, and Robert A. Chase. These are the remarks made by Dr. Robert M. Goldwyn at the commemoration for Dr. White.


Repositioning of prominent ears.

Repositioning of prominent ears. An operation for the repair of prominent ears is presented that includes the best features of the cartilage incision and cartilage suturing techniques. By using the best of several procedures, an operation has been developed which gives consistent, reproducible results in the treatment of prominent ears; and which is easily adaptable for children.


Hyperbaric oxygen in the treatment of burns. Since 1972, over 800 burn victims have been treated with hyperbaric oxygen at the Burn Center of Sherman Oaks Community Hospital in Los Angeles. HBO is used only as an adjuvant to standard resuscitation and is not intended to replace current accepted therapy. The results of the first three-year study program show definite changes in burn care delivery. There has been a definite decrease in the mortality as compared with our own predictions and statistics and with those of the N.B.I.E. In addition, a marked improvement in morbidity and a reduction in hospital stay were noted.


Quantitation of thermoregulatory impairment in patients with healed burns. The basis of our study lies in the clear demonstration that rectal temperature in cool and comfortable environments is a function of the metabolic load but that once a critical level of environmental warmth has been exceeded, the rectal temperature increases above the metabolically controlled level. This effect forms the basis of the presently suggested limits for healthy individuals during heat exposure in industry. We show that impairment of thermoregulation due to extensive burns makes such environmental limits unacceptable. Our experiment was aimed at demonstrating certain tolerance limits above which the extensively burned patient (40% deep second- or third-degree burns) cannot realistically be expected to function under the workload employed. Nine subjects with varying degrees of anhidrosis were subjected to standard workloads under carefully controlled environmental conditions. We found a dramatic diminution in heat tolerance in patients with healed burns covering more than 40% of their body surface area.


Plastic surgery in the twentieth century. Plastic surgical operations are among the oldest and have been developed increasingly from ancient times down to the present. However, the age of medical specialization did not begin until the latter part of the nineteenth century, and the specialty of plastic surgery is largely a child of the twentieth century. Most of the operations we do today have been created by plastic surgeons with the past 50 years, but were made possible only by the rapid developments in other surgical specialties and in all of medicine and science. The relationship with other specialties has been an interdependent one, and this is likely to be the pattern of the future. Plastic surgery, bridging the anatomical specialties as it does, must continue to draw bits of information here and there from them and to synthesize these into major contributions of great benefit to all. The specialty will grow in direct proportion to the success of the innovators within it in fulfilling their crucial role.


Wire basket for immobilization of interscapular skin grafts. One of the most difficult areas on the body to skin graft successfully is the interscapular and upper back region. We have used a wire "basket" to immobilize the interscapular region in 8 patients following wide excision for melanoma. "Takes" amounting to more than 90% in 7 patients and 80% in 1 patient have been obtained. The technique is simple and inexpensive.


Correction of the inverted nipple.

Correction of the inverted nipple. The inverted nipple has been attributed to hypodevelopment of both nipple and areolomamillary musculature. A number of procedures have been devised to correct this deformity for the purposes of nursing and also for cosmesis. Excision of the entire areola, myotomy of areolomamillary bundles, and partial areolar excision in apposing quadrant triangles have all been used. An operative technique has been designed reflecting some of the older methods and an innovation utilizing areolar V-Y plasties and purse-string sutures to the nipple base for support. This method avoids excision and consequent extensive scarring of the areola. This procedure has been found to have satisfactory functional and cosmetic results in clinical trials to date.


Another seventeenth-century denigration of Gaspare Tagliacozzi. Gaspare Tagliacozzi published his carefully documented procedures for nasal reconstruction at the end of the sixteenth century. However, almost all authorities in the succeeding century failed to give him credence. Although his name was widely known, his work became an object of scorn. James Cooke, author of one of the most popular English surgical textbooks of the seventeenth century, in an amusing and previously unnoted reference, adds to this denigration and helps to explain why nasal reconstruction became a subject of satire in England.


Ferris Smith.

Ferris Smith. Important events and renowned persons are seen and remembered differently by those who live the happening or know the person. In As I Remember Ferris Smith, four of his trainees provide a kaleidoscopic view of the doyen.


Mandibular reconstruction with free tissue transfers. During the past ten years, immediate mandibular reconstruction has gradually fallen into disfavor because of the incidence of infection and the increasing use of preoperative radiation therapy. The difficulty lies in selection of the ideal material for mandibular replacement and the attainment of a healthy recipient bed. An attempt has been made to solve this problem with microsurgical techniques, and our experience in six free tissue transfers utilizing both free rib and free osteocutaneous groin flap transfers is reported. The evolution of these techniques has required confirmation of the feasibility of free flaps in the oral cavity as well as incorporation of a vascularized bone graft in free groin flaps. Based on this experience, the free osteocutaneous groin flap containing a vascularized portion of the iliac crest is preferred for reconstruction of combined and composite deficiencies of the lower jaw. Convincing demonstration of bone viability in composite flaps must await correlation of bone scans with tetracycline labelling.


The tensor fascia lata musculocutaneous flap. The tensor fascia lata (TFL) muscle, together with the overlying skin of the anterolateral thigh, makes a reliable musculocutaneous unit. It can be lengthened safely by taking the fascia lata and the skin of the anterolateral mid and lower thigh to within 8 cm of the knee. The skin of the longer flap is supplied by large perforating musculocutaneous arteries, the terminal branches of the vascular pedicle of the muscle. The shorter flap can easily be transposed over the trochanteric area, while the larger flap will cover not only the trochanter but also the ischial and sacral areas. The flap serves equally well as a transposition, island, or free flap. The anatomical and vascular basis of the flap is presented, together with its application in 21 patients. Possible further applications of the flap, including anterior rotation, are discussed.


Congenital absence of the vagina: diagnosis and plastic surgical reconstruction. Congenital absence of the vagina was repaired in twenty patients; the longest follow-up was seventeen years. The surgical method is described, including the skin graft, the sculpted prosthesis, and the mechanic's waste bolus for retention. The patient must be oriented thoroughly before the operation. Even with an optimum surgical result, full cooperation and psychological preparation are necessary to gain a successful transformation. The phrase "psychiatry with a scalpel" is apt in these cases. Ideally, the operation is performed by a team of plastic surgeon and gynecologist. Meticulous planning and regard for detail are fundamental requirements.


"Staircase" closure of lower lip defects. Attention is called to a previously described method of closing certain common surgical defects of the lower lip. Advancement flaps are used from one or both sides, resulting in a staircase configuration. The advantages, disadvantages, and applications of the method are described.


Lower lip reconstruction following resection of large lesions. Good cosmetic and functional results have been obtained following wide resection of large lower lip lesions. A simple method is described for reconstruction.


Massive basal cell carcinoma of the scalp: successful management by cooperation of chemosurgeon and reconstructive surgeon. No single modality is appropriate for treatment of the huge invasive basal cell carcinoma. Mohs' chemosurgery is perhaps the most efficacious ablative method, but it must be supplemented by a reconstructive procedure in nearly all sizable lesions. A case history is presented of a patient with massive basal cell carcinoma involving the entire posterior scalp and deep tissues in which chemosurgical ablation and major staged reconstruction proceeded concurrently to a successful conclusion. The advantages of this approach are discussed.


Kidney transplantation.

Kidney transplantation. Since 1954, more than 26,000 kidney transplants have been performed and transplantation is now an accepted method for the treatment of end-stage renal disease. Recent advances in transplantation include operation not only on ideal recipients, but also on a much broader group of patients; an improved understanding of rejection mechanisms; better employment of standard immunosuppressive drugs; identification of an additional major histocompatibility antigen system; appreciation that blood transfusions prior to transplantation may facilitate acceptance of cadaver kidneys; and development of intracellular washout solutions for kidney preservation. Although the overall functional survival rates of kidney transplants have not improved recently, there has been a significant improvement in patient survival, especially after transplantation of cadaver kidneys.


Comparison between the early use of skin flap and skin graft for the correction of large tissue loss at the elbow. Six patients with soft and hard tissue injuries of the elbow region during the 1973 Yom-Kippur war are discussed. These six patients were treated with two types of procedures. One group was initially treated with application of a split-thickness skin graft followed by a thoracoabdominal, abdominal, or chest skin flap. The second group was initially treated with the application of a thoracoabdominal flap. There are few descriptions in the literature or in textbooks of the plan design method, nor are there comparisons of two types of procedures. In both groups the end results were the same. The differences were the time of hospitalization and the cooperation of the patients during treatment. In both groups the flap was transferred before further surgical reconstruction of bones and joints.


Split groin flap.

Split groin flap. This paper describes the vertical splitting of an axial pattern groin flap, a technical modification which extends the usefulness of this flap in reconstructive surgery of the hand.


Conservation of normal tissue in the treatment of massive basal cell carcinoma. Reconstruction of a defect of the shoulder and chest wall following resection of extensive basal cell carcinoma is demonstrated using classic principles of flap design and delay. Preservation of the normal tissue in an arm before amputation allowed for closure of a wound that could not be covered with musculocutaneous, omental, or microvascular free flaps.


Dr. Theodor Billroth and the first laryngectomy. This short historical vignette gives details of a courageous surgical feat performed by Dr. Theodor Billroth. Long before the advent of modern medical and surgical knowledge, and without the aid of today's advanced medications and instruments, he undertook the first known successful laryngectomy on a human 105 years ago, and five years later he performed the first hemilaryngectomy. In addition to being an outstanding surgeon, Dr. Billroth was also an accomplished musician.


Optimizing the skin graft board.

Optimizing the skin graft board. A skin graft board has been devised, which allows every surgeon to cut grafts of different sizes. Skin grafting is simple to perform and readily learned by trainees both in general and in plastic surgery.


Effect of tranexamic acid on rebleeding after subarachnoid hemorrhage: a double-blind controlled clinical trial. In a double-blind controlled clinical trial on 51 patients with subarachnoid hemorrhage, tranexamic acid, 4 gm per day for ten consecutive days, did not favorably affect the outcome. Neither mortality nor rebleeding rates were improved after a follow-up of three months.


"Disappearing" spinal cord compression: oncolytic effect of glucocorticoids (and other chemotherapeutic agents) on epidural metastases. Four patients suffering spinal cord compression resulting from epidural metastases were treated with adrenocorticosteroid hormones. For 2 patients, prompt relief of symptoms followed glucocorticoid therapy alone and was associated with marked shrinkage or disappearance of the metastasis, a direct oncolytic effect of the steroids. For the other 2 patients, glucocorticoids combined with other chemotherapeutic agents caused disappearance of the extradural tumor. For 1 patient, failure to recognize the oncolytic effects of the chemotherapy led to an unnecessary surgical procedure, and for a second patient an unnecessary operation was narrowly averted. Thus, for certain patients, glucocorticoids may occasionally have a marked oncolytic effect on epidural metastatic tumors.


Idiopathic regressing arteriopathy.

Idiopathic regressing arteriopathy. Three patients had nonatheromatous occlusive cervicocephalic arterial disease which on follow-up showed resolution of the occlusive or stenosing abnormalities. The patients' relatively young age (middle thirties to middle forties) and severe unilateral headache or focal head, neck, or mastoid pain were prominent common clinical features. The dominant arteriographic features were intimal irregularities, multiple vessel involvement, tendency to arterial dissection and aneurysm formation, sparing of intracranial arteries, and tendency to partial or complete resolution of the abnormalities and regression toward normal. We have called this presumed entity "idiopathic regressing arteriopathy" pending appropriate histopathological studies.


Rapid improvement in nerve conduction velocity following renal transplantation. In 12 patients with chronic renal failure who received kidney transplants from either cadavers (6) or related living donors (6), rapid improvement in median sensory and motor nerve conduction velocities (NCVs) was observed within a few days after transplantation. The postoperative improvement in median sensory NCV was found to bear a statistically significant negative correlation with creatinine and myo-inositol concentrations. We suggest that metabolic phenomena are responsible for the rapid improvement in median sensory NCV following renal transplantation. The close relationship between myo-inositol and the median sensory NCV following transplantation suggests that elevated plasma myo-inositol concentrations may be related to nerve conduction abnormalities in uremic polyneuropathy.


Bell's palsy and secondary syphilis: CSF spirochetes detected by immunofluorescence. Although Bell's palsy is usually idiopathic, occasional cases may have an identifiable infectious cause. When facial paralysis results from syphilis, it usually develops during the tertiary meningovascular stage. We report a 30-year-old man with secondary syphilis who developed facial paralysis associated with acute syphilitic meningitis. Spirochetes were identified in the cerebrospinal fluid by immunofluorescence using standard reagents from the fluorescent treponemal antibody absorption (FTA-ABS) test. Patients with Bell's palsy should be screened for syphilis with a blood FTA-ABS test, and treatment with corticosteroids should be considered only after an infectious cause has been excluded.


[Plasmids of antibiotic-resistant clinical strains of E. coli]. Analysis of 53 antibiotic resistant clinical strains of E. coli isolated from patients with various purulent inflammatory diseases is presented. According to the data of the electrophoretic study 83 per cent of them carried 2 to 6 plasmids. Thirteen of them carried the conjugation R-factor. The antibiotic resistance in the other strains was due to the non-conjugation plasmids.


[Leukolysis reaction in the diagnosis of allergy to antibacterial preparations in pulmonology]. The experiment included 109 patients with non-specific pathological processes in the lungs. i.e. 21 cases with acute and 55 cases with chronic pneumonia and 33 cases with bronchial asthma with or without chronic pneumonia. Clinically intolerance of the antibacterial drugs was observed in 39 patients and increased leucolysis (above 15 per cent) was observed sometimes more frequently. Only with the use of penicillin the difference was 1.6 times. Out of 39 patients with clinical signs of allergy to antibiotics or sulphanilamide only 20 showed the signs of increased leucolysis on the use of the respective drug. No correlation between the percentage of the leucolysis cases due to antibiotics or sulphanilamides and the clinical signs of their intolerance was observed. The use of such drugs by a person or even only his presence in the hospital often induced increased leucolysis which may be considered as an indication of the person sensibilization to them.


Synergistic activity of gentamicin with trimethoprim or sulfamethoxazole-trimethoprim against Escherichia coli and Klebsiella pneumoniae. The effect of combinations of gentamicin with trimethoprim or sulfamethoxazole-trimethoprim against clinical isolates of Escherichia coli (11 strains) and Klebsiella pneumoniae (12 strains) was examined by using a microdilution checkerboard technique. All isolates were susceptible to each antimicrobial agent. Synergism, defined as at least a 2-log(2)-dilution lowering of the minimal inhibitory concentration of either antibiotic in the combination compared with the minimal inhibitory concentration of the antibiotic alone, was observed with 15 of 23 (65%) isolates tested against trimethoprim and gentamicin and 14 of 23 (61%) isolates tested against sulfamethoxazole-trimethoprim and gentamicin. A 3-log(2)-dilution lowering of the minimal inhibitory concentration of either antibiotic was observed in 7 of 23 (30%) trimethoprim and gentamicin trials and 3 of 23 (13%) sulfamethoxazole-trimethoprim and gentamicin trials. Antagonism was observed in 3 of 46 combination trials and only with strains of K. pneumoniae.


Interaction of chemotherapy and immune defenses in experimental murine cryptococcosis. Congenitally athymic nude (nu/nu) and thymus-containing heterozygous (nu/X) mice were infected intraperitoneally with Cryptococcus neoformans over a wide range of challenge doses. Cryptococcal disease progressed more rapidly in nude mice than in their nu/X littermates. When nu/X mice were treated with amphotericin B, all survived an otherwise lethal dose of C. neoformans. At larger challenge doses, survival was prolonged in nu/nu mice treated with amphotericin B, but they later succumbed to cryptococcosis. At lower challenge doses, amphotericin B was curative in some nude mice. Therapy of nude mice with both amphotericin B and flucytosine further prolonged survival at high-dose challenge and increased the number of cures at low-dose challenge. These studies support an interaction of antifungal chemotherapy with thymus-dependent immune defense mechanisms. This interaction is most evident at high challenge doses, where antifungal chemotherapy cures nu/X mice but only modestly prolongs survival in nude mice.


Effect of feeding chlortetracycline on the reservoir of Salmonella typhimurium in experimentally infected swine. Swine were fed either a diet containing 110 mg of chlortetracycline (CTC) per kg (100 g/ton) or a control diet and were inoculated orally with Salmonella typhimurium that was either susceptible or resistant to CTC. The quantity, duration, and prevalence of fecal elimination of S. typhimurium, as well as the effect of CTC on the transmission of S. typhimurium from infected to uninfected swine, were determined. When animals were infected with CTC-resistant S. typhimurium, CTC increased the quantity (P < 0.05), duration (P < 0.05), and prevalence (P < 0.01) of fecal shedding, the transmission from infected to uninfected swine, and the recovery of the infecting organism at necropsy. When animals were infected with CTC-susceptible S. typhimurium, CTC reduced the quantity (between 7 and 10 days postinfection) (P < 0.01), duration (P < 0.05), and prevalence (P < 0.05) of fecal shedding, the transmission from infected to uninfected swine, and the recovery of the infecting organism at necropsy. Resistance to tetracycline was transferred in vivo to 4 and 6% of the susceptible infecting S. typhimurium recovered from the untreated and treated groups, respectively. The increased reservoir of S. typhimurium and the transfer of resistance to susceptible S. typhimurium have implications for both animal and public health.


Genetic and molecular characterization of an Escherichia coli plasmid coding for hydrogen sulfide production and drug resistance. An H(2)S-producing variant of Escherichia coli (strain 142) isolated from a urinary tract infection was found to be resistant to high levels of tetracycline, ampicillin, streptomycin, and sulfonamide. The H(2)S trait segregated spontaneously at a frequency of 2.5 x 10(-3). No segregation was observed for the drug resistance determinants. Neither ethidium bromide nor acridine orange affected the rate of segregation of the drug resistance determinants or the trait for H(2)S production. Antibiotic resistance and hydrogen sulfide production were conjugally transferred to E. coli K-12 recipients at a frequency of approximately 10(-5) per donor cell. Antibiotic resistance and hydrogen sulfide production were also transduced as a single unit with phage P1L4. Genetic data, based on the segregation of resistance determinants and the H(2)S trait among transconjugant and transductant classes, suggested the presence of two R plasmids. Plasmid DNA was isolated by cesium chloride-ethidium bromide centrifugation. Two plasmid species were detected by agarose gel electrophoresis of purified plasmid DNA, a large molecule of about 80 x 10(6) daltons (designated pSR12) and a small molecular species of approximately 5.5 x 10(6) daltons (designated pSR13). Transformation studies using purified plasmid DNA showed that the large pSR12 plasmid confers resistance to ampicillin, tetracycline, and streptomycin and also carries the gene(s) for H(2)S production. The small pSR13 plasmid confers resistance to streptomycin and sulfonamide.


New cephamycin antibiotic, CS-1170: binding affinity to penicillin-binding proteins and inhibition of peptidoglycan cross-linking reactions in Escherichia coli. The binding activity of CS-1170, a new cephamycin antibiotic, to penicillin-binding proteins (PBPs) in Escherichia coli and Proteus species and the potency of this antibiotic in vitro to inhibit enzymes involved in peptidoglycan cross-linking in E. coli were tested. Similar experiments were carried out with the 7alpha-H analog of CS-1170, R-45656, and the results were compared with those obtained with CS-1170. CS-1170 showed high affinities (compared with that of penicillin G) for E. coli PBP-1A, -1Bs, and -3, the PBPs of higher molecular weight, but not PBP-2. It also inhibited the in vitro peptidoglycan cross linking reaction and concomitant release of d-alanine at very low concentrations (approximately its minimal inhibitory concentration). This antibiotic also showed very high affinity for PBP-4, -5, and -6, the PBPs of lower molecular weight, and at extremely low concentrations it inhibited d-alanine carboxypeptidases IA and IB, corresponding to PBP-5/6 and PBP-4, respectively. CS-1170 seemed to be resistant to the beta-lactamase activity of PBP-5 and -6 in E. coli and Proteus species. R-45656 showed as high an affinity for PBP-1A, -1Bs, and -3 as CS-1170, but unlike CS-1170, it had low affinities for PBP-4, -5, and -6. The concentrations of R-45656 required for inhibition of d-alanine carboxypeptidases IA and IB were also much higher than those of CS-1170. R-45656 showed rather low activities in inhibiting the in vitro cross-linking reaction of peptidoglycan and concomitant release of d-alanine. Synergism was observed in 9 of 22 strains examined between CS-1170 and mecillinam, which bound specifically to PBP-2.


Colicinogeny of Escherichia coli MRE 600. Escherichia coli MRE 600 is a colicinogenic bacterium. Its colicinogenic activity may be ascribed mostly to colicin E1, although it produces a small amount of another, as yet unidentified, colicin.


Combined stereotactic and peripheral surgical approach for spasmodic torticollis. Thalamotomy with or without pallidotomy and peripheral denervation, if necessary, was performed in 14 cases of spasmodic torticollis or other late dystonias. Of 4 bilateral procedures, 2 had a good result, in 1 there was little change and in another the patient remained with a pseudobulbar syndrome, the only complication in this group. 1 patient only required peripheral denervation with a good result. Of the 9 patients who underwent unilateral thalamotomy, with or without pallidotomy, the result was excellent in 6 and good in 2 others, but in 4 of these 8 patients peripheral denervation was also performed.


A new apparatus to avoid certain complications in stereotactic operations at the upper cervical spinal cord. An electronic apparatus was developed which measures the effective current flow of the monophasic stimulation pulses while the tip of the electrode is passing through the tissue. This current flow can be observed as a function of time on the screen of a cathode ray tube.


Application of stereotactic principles to the treatment of trigeminal neuralgia. The application of neuroanatomical and neurophysiological principles to the functional surgery of the trigeminal nerve is discussed. Particular attention has been directed toward correlating the three-dimensional anatomical features of the trigeminal nerve and the surrounding structures to the two-dimensional radiograph of this same region. In this regard, 20 trigeminal nerves, including the surrounding neurovascular structures from 10 cadaver sphenoid blocks, were examined. Measurements of the third, fourth and sixth cranial nerves in relation to the profile of the clivus were made from lateral radiographs of the sphenoid blocks. The position of the internal carotid artery in relation to these structures was also noted. These neurovascular relationships are of clinical importance when using the percutaneous thermocoagulation technique for the treatment of trigeminal neuralgia.


Computer-assisted stereotactic brain operations by means including computerized axial tomography. With a computerized program system for stereotactic brain operations it becomes possible for the first time to react even before running a possible risk, e.g., in case of punctures in the midbrain, the brain stem, or in the hypothalamus, by simulating the operative procedure even before starting the operation itself. This is effected by the ability to change the penetration angle of the electrode or by choosing a different point of trepanation. The inclusion of computerized axial tomography, especially through the presentation of the CT scan, made to measure with the help of the linear transformation, and of the input of the cranial and ventricular coordinates through a digitizer, together with the coordinates resulting from the X-ray picture, brings the definition of the target point to a still greater optimum. Thus the safety and the precision of the stereotactic operation have been improved even further.


Computerized graphic display of physiological data collected during human stereotactic surgery. An on-line computerized graphic display has been developed for use during stereotactic operations. This depicts in the form of figurine charts and alph-numeric symbols, appropriately oriented on saggital brain diagrams, the results of serial threshold stimulation of the brain. The display facilitates choice of target sites and the data can be stored in a tape library from which search-and-plot programs can be activated for any type or combination of types of response.


Estimation of neural noise. Functional anatomy of the human thalamus. In the course of stereotactic thalamotomy, the neural noise level of subcortical structures was estimated quantitatively with the aid of two semimicro-electrodes. The neural noise showed several characteristic features in terms of its amplitude and discharge pattern so that it was correlated with the possible anatomical substrate, thus providing the functional anatomy of the subcortical structures. The study on saggital plane revealed a systematic difference of the noise level between VL and Vim-Vc that could be explained by the different cell size in respective nucleus. Several exceptional cases were also presented, emphasizing the neural noise study in stereotactic surgery.


Arrest reaction in man. Motor arrest response by electrical stimulation of the deep structure of the cerebrum. In spite of many reports of arrest reaction in animals, there are very few reports in man. During a therapeutic stereotactic operation we observed peculiar phenomena caused by electrical stimulation to the deep structure of the cerebrum. This phenomenon is quite similar to that reported by Van Buren, but there are a few differences between them. Arrest reaction was observed in 14 of 23 cases, 17 of 28 tracks. Stimuli which caused the arrest reaction were 60--100 Hz square waves of 1 msec duration and 5--15 V. The electrical stimulation caused an interruption of counting and other motor actions, which could be resumed following release of stimuli. Psychic confusion or memory disturbances were not observed with the exception of a few cases. The arrest reaction that we observed is thought to be due to a direct effect on the head of the caudate nucleus, not due to secondary effects on the internal capsule and the motor fiber in vicinity of the caudate nucleus. However, the possibility that the current spread to the motor fiber cannot be definitely ruled out.


Stereotactic radiofrequency hypophysectomy. Clinical indications and technical details of RF hypophysectomy were reviewed. Evaluation of serveral hundred procedures toward pathologic and symptomatic amelioration ofmetastatic breast cancer and diabetic retinopathy, and also a few cases of intrasellar tumor, indicated sufficient benefit for endorsement in selected patients.


The posteromedial hypothalamus and pain, behavior, with special reference to endocrinological findings. Stereotactic intervention into the posterior hypothalamus gives satisfactory results for controlling both aggressive, violent behavioral disorders and intractable pain. From the endocrinological point of view, this procedure activates the hypothalamic-hypophyseal axis only temporarily, without causing any serious dysfunctions.


Surprise finding 5 years after stereotactic amygdalotomy. Before extinction of an epileptogenic focus exclusion of an intracranial tumor or an angioma by EEG, isotope and contrast medium diagnosis must be attempted. A case history is presented of a patient in whom a malignant glioma was discovered 5 years after stereotactic treatment for epilepsy.


Stereotactic amygdalotomy for convulsive and behavioral disorders. Long-term follow-up study. 58 patients, whose convulsions and behavioral disorders did not respond to nonsurgical therapy, were treated with stereotactic amygdalotomy between 1963 and 1973. A retrospective study was carried out by a psychiatric research team 1--11 years postoperatively. Using reliable objective methods of assessment they found that 50% operated primarily for seizures, 33% for uncontrolled conduct disorders and 50% with both conditions seemed improved after surgery.


Changes in regional cerebral blood flow following stereotactic psychosurgery. Serial measurements of regional cerebral blood flow by the 133Xe inhalation method were performed in a pilot study in 6 patients undergoing stereotactic psychosurgical procedures (anterior capsulotomy, cingulotomy, frontobasal tractotomy). Average hemispheric flow did not change significantly from pre- to post-operative, but changes were seen in the patterns of regional flow distribution. The most striking finding was frontal flow reduction following capsulotomy. In view of the coupling of blood flow and function in the brain, the results indicate that this method offers a new way for exploring the effects of functional neurosurgery on brain activity.


Stereotactic cingulumotomy for drug addiction. This paper analyzes the results of surgical treatment of 73 patients with drug addiction. They were treated by lesions in the anterior cingulum. Morphine, Pethidine (meperidine) and alcohol were the common drugs of addiction. Selection of cases, rationale for surgery and operative technique are discussed. Follow-up varied from 1 to 6 years. Results of surgery indicate this procedure as the most promising one for cure of drug addiction.


Influence of stereotactic hypothalamotomy on alcohol and drug addiction. 2 or 3 years follow-up of 13 hypothalamotomy patients with alcohol and drug addiction reveals that the addicted patients regained their self-control, the severe preoperative social deterioration was removed, and the tendency to social stabilisation was clearly in evidence.


Spinal cord stereotactic techniques re trigeminal nucleotomy and extralemniscal myelotomy. The application of stereotactic techniques to the spinal cord as a logical sequel to percutaneous procedures have produced significant developments by enabling the functional exploration of different cord structures. Radiofrequency lesions were placed either at the spinal trigeminal nucleus, for facial pain of central origin such as postherpetic neuralgia or anesthesia dolorosa as well as for neoplastic pain of extensive craniofacial distribution, or at the central cord region to interrupt preferentially multisynaptic nonspecific pathways mainly for midline and/or bilateral pain but also for patients with respiratory inadequacy or for certain central pain states. Technical aspects are reported, and physiological correlates relevant to surgery are analyzed. Results, indications and limitations are discussed.


Mollicellins: mutagenic and antibacterial mycotoxins. Eight mollicellins (depsidones) were assayed for mutagenicity and antibacterial activity in Salmonella/microsome tests involving histidine reversion and forward mutation to 8-azaguanine resistance. Two of them, mollicellins C and E, which contain a 3-methylbutenoic acid moiety, were mutagenic and bactericidal for Salmonella typhimurium in the absence of microsomes. Mollicellins D and F, each containing a chlorine atom, were bactericidal but not mutagenic. The mutagenic activity was completely abolished and the antibiotic activity was greatly reduced by coincubation with rat liver microsomes.


Enchanced accuracy of coliform testing in seawater by a modification of the most-probable-number method. A 1-year study of marine water sample from six beach locations showed that the most-probable-number method failed to recover significant numbers of coli-forms. Modifying this method by transferring, after 48 h, presumptive negatives (growth and no gas production) to confirmed and fecal coliform media significantly improved recovery. Tests which were presumptive negative but confirmed as fecal coliform positive were designated as false negatives. Most-probable-number method false negatives occurred throughout the year, with 143 of 270 samples collected producing false negatives. More than 50% of fecal coliform false-negative isolates were Escherichia coli. Inclusion of false-negative tubes into the coliform most-probable-number method data resulted in increased violation of the California ocean water contact sports standard at all sites. More than 20% of the samples collected were in violation of this standard. These data indicate that modification of the most-probable-number method increases detection of coliform numbers in the marine environment.


Primary Klebsiella identification with MacConkey-inositol-carbenicillin agar. MacConkey-inositol-carbenicillin agar has successfully been used as a primary selective medium for Klebsiella enumeration. With pure cultures, nearly 100% recovery of Klebsiella was observed by membrane filtration. With environmental samples using membrane filtration, 95% of typical pink- to red-colored colonies were verified as Klebsiella, as opposed to only 1% of yellow background colonies. Recovery of Klebsiella on MacConkey-inositol-carbenicillin agar was as good or better than on mEndo agar LES (Difco Laboratories). Recovery and percent colony confirmation with MacConkey-inositol-carbenicillin agar were greater than for other proposed Klebsiella selective media.


Surface kinetic test method for determining rate of kill by an antimicrobial solid. An antimicrobial-surface kinetic test which maximizes probability of cell-to-surface contact has been developed. The measurement of rate of kill by a nonleaching antimicrobial surface is based on the number of surviving bacterial cells at specific times of exposure to various amounts of total treated surface area of test substrate. This method gives information for direct comparison of rate of kill for a variety of antimicrobial surfaces in terms of rate of kill per square centimeter of surface area. Data obtained by this method can also give valuable dose response application information as an indication of the exponential efficiency of concentration in terms of treated surface area.


Dry-heat destruction of lipopolysaccharide: mathematical approach to process evaluation. A mathematical model was developed to estimate the number of logarithmic cycles (LDec) of lipopolysaccharide concentration destroyed by a dry-heat sterilization process. The LDec values calculated from the mathematical model agreed well with those obtained from the destruction of lipopolysaccharide by a dry-heat treatment. A discussion of how the mathematical model may be used to evaluate a dry-heat sterilization cycle is presented. This mathematical model and the dry-heat destruction curves indicated existence of a maximum LDec value at each temperature. The implications of this finding are discussed.


Lactose variability of Escherichia coli in thermally stressed reactor effluent waters. Lactose-utilizing and nalidixic acid-resistant populations of Escherichia coli, having an optimum growth temperature of 37 degrees C, were placed in modified diffusion chambers. The chambers were submerged in the epilimnion and hypolimnion of a 1,100-hectare lake (Par Pond) which receives cooling water from a nuclear production reactor. Control chambers were placed in a deep-water reservoir and a Flowing-Streams Laboratory, both of which had comparable temperatures to Par Pond. The populations of E. coli were sampled regularly for up to 3 weeks. Viability of the bacteria was determined by dilution plating to nutrient agar followed by replicate plating onto selective medium to determine lactose utilization and nalidixic acid sensitivity. Initial populations of E. coli were lactose positive but changed to lactose negative in Par Pond when the reactor was operating (i.e., cooling water from the heat exchangers was being discharged to the lake). This alteration occurred most rapidly in the chambers closest to the cooling-water discharge point. Such changes did not occur in a deep-water reservoir, in Par Pond when the reactor was not operating, or in the Flowing-Streams Laboratory. The nalidixic acid-resistant characteristic remained stable regardless of the chambers' placement or reactor operations. Although the reasons for such alterations are unclear, it appears that lactose-negative populations of E. coli are selected for in these reactor effluent waters. The loss of the lactose characteristic prevents the recognition and identification of E. coli in this cooling lake (when the reactor is operating) and may prevent the assessment of water quality based on coliform recognition.


Cystic fibrosis, atopy, and airways lability. In a survey of cystic fibrosis (CF) in the Avon area, 48 children with CF from 40 families together with 71 of their parents were studied by spirometry, exercise tests, and pinch tests. A control group of 42 young adults was similarly tested; control data for children were taken from previously published work. The prevalence of atopy (any positive prick test) in children with CF was 48%. Sensitivity to grass pollens and house dust mite was no more common in these children (29%) than in a normal population (34%). Hypersensitivity to Aspergillus fumigatus was found in 35% of children with CF and was associated with severe lung disease. The parents had a normal pattern and prevalence of atopy. Exercise-induced airways obstruction was present in only 22% of children with CF; its association with severe lung disease rendered interpretation difficult. The parents had a normal response to exercise. Both hypersensitivity to A. fumigatus and exercise-induced airways lability had the features of acquired characteristics. There was nothing in the present study to support the hypothesis that the possession of a CF gene predisposed to atopy.


The functional importance of sympathetic nerves to the liver and endocrine pancreas. Sympathetic noradrenergic nerves, with their wellknown cardiovascular effects, have recently been found to influence several metabolic and hormone-releasing processes. Morphological investigations in man have revealed a dense sympathetic innervation of the liver parenchyma as well as sympathetic fibers among the endocrine cells in the islets of Langerhans. Functional studies both in animals and man have shown that electrical or reflex activation of the hepatic and pancreatic sympathetic nerve fibers causes an increased output of glucose from the liver as well as a stimulation of glucagon and an inhibition of insulin release from the pancreas. From these results we conclude that damage to sympathetic nerves should be avoided in abdominal surgery.


Rapid test for diagnosis of syphilis by means of the surface fixation method using as antigens VDRL and Treponema pallidum (strain Nichols). An attempt to use the "surface fixation" method for the detection of antigen-antibody reactions with VDRL and Treponema pallidum has given results which corroborate conventional serological findings in patients suspected of being infected with this organism. The test is performed over strips of filter paper in which mixtures of the serum with the antigen are deposited and submitted to a special procedure of staining in order to detect antigen-antibody reactions.


Changes in the rate of synthesis of wall polysaccharides during the cell cycle of yeast. Reevaluation and comparison of seemingly contradictory literature data on the mode of synthesis of wall polysaccharides during the cell cycle of Saccharomyces cerevisiae explained the source of discrepancies and demonstrated their general consonance in the following points: 1. The rate of synthesis of glucan and mannan is not constant and does not increase continuously throughout the entire cell cycle. 2. The rate of synthesis of both polysaccharides is considerably reduced at the time of cell division and in the prebudding phase.


[Differentiation of influenza virus antigens using enzyme immunoassay]. Reported is a microprocess of enzyme immune assay in which slipformed air pockets of polyvinylchloride (PVC), as used in the pharmaceutical industry, are used as carriers of antigens or antibody. Two methods, the anti-globulin and the double-antibody methods, are based on antibody which had been coupled with alkaline phosphatase. Tests in which various sub-types of influenza virus were used have shown the double-antibody method to be a sensitive technique which can be successfully used in the differentiation of envelope antigens.


[Radial hemolysis in the diagnosis of influenza virus infections]. Some of the parameters of the radial haemolysis test were studied, and the test was used to determine antibody titres of sera obtained from patients involved in the epidemic outbreak of influenza-A/Port Chalmers, 1975. The sensitivity of the method was found to depend on the degree of erythrocyte sensitisation. An enlargement by 40 per cent of the haemolytic halo diameter should be considered and treated as antibody rise, if the reaction was to used in serological diagnosis under the conditions tested. The findings were in agreement with the complement fixation reaction in 48 per cent of all cases and with the haemagglutination inhibition test in 53.8 per cent.


A last link to Pavlov: W. Horsley Gantt reflects. The work of Dr W. Horsley Gantt, a pioneer in psychophysiology, is reflected in seven books and more than 700 publications. In an interview videotaped in 1976, Gantt commented on his work with Ivan Pavlov, his concepts of schizokinesis and autokinesis, and goals for future scientific investigation within one area of preventive psychiatry.


Meditation and psychotherapeutic effects. Self-regulation strategy and altered state of consciousness. We review the research literature dealing with the psychotherapeutic effects of meditation. The first part of the article reviews studies in which meditation is viewed as a self-regulation strategy. In the second part, studies in which meditation is viewed as a technique for inducing altered states of consciousness are reviewed. We conclude by giving guidelines and suggestions for future research.


Clinical evaluation of naltrexone treatment of opiate-dependent individuals. Report of the National Research Council Committee on Clinical Evaluation of Narcotic Antagonists. A multiclinic controlled trial of naltrexone in opiate-dependent persons led to these conclusions: (1) a narcotic antagonist is an acceptable treatment for a small number of patients undergoing treatment for opiate dependence; (2) the group most likely to be candidates for such treatment are those who are relatively opiate-free ("post-addicts") and well motivated to seek treatment; (3) although differences between patients treated with placebo and naltrexone were slight, both retention in treatment and opiate-free urine tests favored the naltrexone group; (4) adverse effects of relatively short-term treatment were slight, largely being symptoms and signs of precipitated abstinence in patients with residual dependence.


Methylphenidate vs dextroamphetamine vs caffeine in minimal brain dysfunction: controlled comparison by placebo washout design with Bayes' analysis. Double-blind crossover comparison of methylphenidate hydrochloride, dextroamphetamine sulfate, and caffeine after placebo washout in 29 children with minimal brain dysfunction (MBD) showed on six ratings that methylphenidate and dextroamphetamine were significantly (P less than .05 to P less than .001) better than placebo and caffeine, but not significantly (P less than .05) different from each other. Placebo, caffeine, and ratings before drug did not differ significantly. Of 26 drug responders, 12 responded best to dextroamphetamine, ten to methylphenidate, and one to caffeine. The latter child showed no improvement at all with either prescription stimulant. Methylphenidate and dextroamphetamine were each efficacious for six children who did not respond to the other stimulant. All three drugs showed significant (P less than .05) weight loss and cardiovascular side effects, the latter possibly spurious. Dextroamphetamine showed a significant (P less than .05) decrease from placebo in "tummyaches."


Psychophysiological correlates of the practice of Tantric Yoga meditation. Autonomic and electroencephalographic (EEG) correlates of Tantric Yoga meditation were studied in three groups of subjects as they progressed from normal consciousness into meditation. Groups differed in their level of meditation proficiency. Measures of skin resistance, heart rate, respiration, autonomic orienting responses, resting EEG, EEG alpha and theta frequencies, sleep-scored EEG, averaged evoked responses, and subjective experience were employed. Unlike most previously reported meditation studies, proficient meditators demonstrated increased autonomic activation during meditation while unexperienced meditators demonstrated autonomic relaxation. During meditation, proficient meditators demonstrated increased alpha and theta power, minimal evidence of EEG-defined sleep, and decreased autonomic orienting to external stimulation. An episode of sudden autonomic activation was observed that was characterized by the meditator as an approach to the Yogic ecstatic state of intense concentration. These findings challenge the current "relaxation" model of meditative states.


Temperature biofeedback in the treatment of migraine headaches: a controlled evaluation. After an initial four-week baseline phase, during which daily records of headache frequency and intensity and daily medication records were kept, 30 patients with frequent (at least one per month) migraine headaches were randomly assigned to three conditions: (1) temperature biofeedback, autogenic training, and regular home practice; (2) progressive relaxation with regular home practice; and (3) a waiting-list control condition. Comparisons of headache data from the four weeks of baseline and last two weeks of treatment showed that both the relaxation and biofeedback groups improved significantly on total headache activity, duration of headaches, and peak headache intensity and reduced consumption of analgesic medication, while the waiting list control group did not. All three groups showed significant decreases in headache frequency. Although the relaxation training was more effective than biofeedback training at the last week of treatment, follow-up data at one, two, and three months showed no differences between the two treated groups on any dependent measure.


Imipramine and desipramine in plasma and spinal fluid: relationship to clinical response and serotonin metabolism. In a double-blind study of depressed patients treated with imipramine hydrochloride, levels of imipramine and desipramine were measured in plasma and in CSF. Levels of both drugs in CSF were approximately 10% of plasma levels, but the levels in the two body fluids were highly correlated. The levels of both drugs were approximately equal in plasma, but desipramine predominated in CSF (imipramine/desipramine ratio of 0.8). The imipramine-induced alteration in CSF levels of the serotonin metabolite (5-hydroxy-indoleacetic acid [5HIAA]) correlated with imipramine levels but not with desipramine. For the group of patients showing a clear antidepressant response, the mean drug levels were nearly double those of the nonresponder group, a difference that did not quite reach statistical significance in this relatively small sample. The desipramine levels showed no responder-nonresponder difference, while the ratio of imipramine/desipramine was significantly higher among the responders. On the average this particular patient group had relatively low pretreatment levels of 5HIAA in CSF, an observation that may partially account for the relatively low overall response rate to imipramine.


Clinical pharmacology of phenelzine.

Clinical pharmacology of phenelzine. There is renewed interest in the clinical pharmacology of phenelzine sulfate and other monoamine oxidase (MAO) inhibitors. Newer clinical and analytic techniques recently have been applied to investigations of this class of drugs in man. The results show that drugs such as phenelzine are effective in nonendogenous depression and phobic disorders. Clinical response to phenelzine is related to platelet MAO inhibition and dosage per unit body weight. High percent MAO inhibition in platelets at two weeks is associated with greater improvement after a six-week course of treatment. Our data show that a safe, effective phenelzine dose in 1 mg/kg body weight per day. These results have delineated the pharmacologic and therapeutic effects of phenelzine and support a continuing role for MAO inhibitors in psychopharmacology.


Cell membrane ionic permeability, calcium ion, mitochondria, and carcinogenesis. The interrelations between changes in cell membrane permeability, increase of intracellular concentration of calcium ion and alterations of the bioenergetic and genetic mechanisms of the mitochondria are formalized in a hypothesis of carcinogenesis. It seems very likely that changes in the permeability of the cell membrane induced by the carcinogen are responsible for increased intracellular accumulation of Ca2+. This phenomenon produces mitochondrial damage associated with permanent modifications of the structural and functional characteristics of the cell membranes as well as of the genetic mechanisms controlling cell division.


Kidney glomerular pathology in various forms of acute and chronic hepatitis. Kidney tissue from 99 unselected necropsy cases of various forms of hepatitis and liver cirrhosis was examined by histology and direct immunofluorescence. Glomerular deposits of hepatitis B surface antigen (HBsAg), IgG, IgM, and complement were found in nine of 59 cases (15%) of acute and subacute hepatitis and in seven of 40 cases (17%) of chronic aggressive hepatitis and liver cirrhosis. Different amounts of granular hepatitis B surface antigen immune deposits were distributed along glomerular capillary walls and/or in mesangial areas. Glomerular lesions found in these cases consisted of thickening of glomerular capillary walls, a slight increase in glomerular cellularity, and an increase of mesangial matrix. These glomerular lesions are considered to result from the humoral immune elimination of circulating viral surface antigen immune complexes.


Improved technique for cutting brain slices. When two disposable serological pipettes with an external diameter of 1 cm are placed on the cutting surface on either side of the brain and the knife rides across them, it will cut even slices precisely 1 cm thick. Both coronal and horizontal slices can be cut as well as oblique slices for comparison with computerized tomographic scan roentgenograms although for the latter the initial cut will have to be made freehand. For practical purposes, brain slices obtained by this simple technique are as good as those made with a mechanical jig or electric machine and are superior to those made freehand.


[The revascularisation of fresh homologous bone grafts in the diaphysis of long bones in dogs (author's transl)]. In two series each 5 X 2 grown up mongrel dogs we studied the healing process of fresh concellous and cortical homografts in a defect made in the diaphysis of the radius bone. The experiments cover microangiographical and histological weekly control in the first 6 weeks after transplantation. The results demonstrate that the fresh concellous homografts have a good revascularisation and produce early new bone in the first week. The revascularisation of the cortical grafts is delayed. The immune reaction, which begins after two weeks, is in concellous bone graft more vigorous than in the cortical graft. The reaction leads to vascular disruption prior to the degenerative and necrotic changes of the tissue cells in the grafts including the new bone formation. After overcoming the immune reaction the 2nd or the so called inductive phase of new bone formation starts. The integration of cortical grafts in the host bone is much slower than in concellous bone graft. The vigorous immune reaction followed by the avascular interval in the concellous homografts between the second and third week must be considered as a dangerous critical phase when using homografts in the clinic. Because of the less cell concentration in the cortical homografts there is less immune reaction. Revascularisation in cortical homografts is slow and consequently there is a delayed incorporation of the grafts in the clinical use.


[Results of resection, analogous bone grafting and osteosynthesis of juvenile bone cysts (author's transl)]. Drawing the conclusions from the results we can say on the basis of the material presented that in the treatment of the solitary bone cyst the total resection of the cyst is more advisable than the excochleation. If the cysts are closely located to the epiphyseal cartilage it will, however, not always be possible to avoid relapses, even if a total resection has been carried out, since the simultaneous resection of the epiphyseal cartilage would result in defective growth. Here the final correction is, however, possible by a second operation, when the cyst has grown further away from the epiphyseal cartilage. The shortening of extremities observed by us are to be attributed to partial damages of the epiphyseal cartilage on account of the operation and may be avoided by a more careful operation procedure. On the whole, the total resection with analogous bone grafting and osteosynthesis can be recommended as a well-tested method of operation with the purpose of obtaining a complete and lasting recovery.


Liver allograft. Its use in chronic active hepatitis with macronodular cirrhosis, hepatitis B surface antigen. A patient suffering from chronic active hepatitis with macronodular cirrhosis, positive for hepatitis B surface antigen (HBsAg), was treated with an orthotopic liver allograft. The HBs antigenemia, as measured with several precipitation tests and by complement fixation, became negative after transplantation and remained so for about 2 1/2 months. During the interval, very low titers of the antigen were detectable by radioimmunoassay. At about three months after transplantation, she had an attack of acute hepatitis, at which time HBsAg became detectable by all tests. She recovered, but progressive liver disease developed during the remaining 1 1/2 years of her life. She died of disseminated nocardiosis and candidiasis with deteriorating hepatic function. The homograft at autopsy showed no evidence of rejection, but was the site of chronic active liver disease, although of a different pathologic pattern than that affecting her native liver. The differences in histology may reflect the influence of chronic immunosuppression on the features of chronic active hepatitis.


[Ultrastructural analysis of rat pancreatic islet B-cells following thyroidectomy]. Electron microscopic investigations have shown that after 5 days the pancreatic B-cells of thyroidectomized rats are characterized by marked endoplasmic reticulum dilatations, the reduction of Golgi complex, and the secretory granule extrusion into pericapillary spaces. Later (after 30 days), the insuline granule extrusion from B-cells is retarded, and an increased number of mielin figures in the cytoplasm is observed.


[Chief types of placental trophism].

[Chief types of placental trophism]. An attempt is made to represent a theory on two types of placental throphism. The first type--nutrition is mainly performed at the expense of maternal proteins, which in the placental chorion undergo proteolysis with formation of polypeptides and amino acids; embryospecific proteins are formed in the liver of the embryo. This type is characteristic for the animals with epithelio-chorionic acid and partly with desmo-chorionic placentas. The second type is characterized by resorption of amino acids from the maternal organism, from the latter embryospecific proteins are synthesized in the chorion. Thus, placental nutrition is specific for man and animals with hemochorionic and, partly, with endothelio-chorionic placentas.


[Changes in gastrulation processes during phylogenesis in the animal world]. While treating gastrulation only as the entoderm individualization and formation of a double layer germ we do not take into consideration the alterations which gastrulation process has undergone in phylogenesis of different animal types. On the other hand, if entoderm formation (in vertebrates--with discoblastula) is not included in the notion of gastrulation, it will result in a complete incompartibility of gastrulation processes in other groups of animal kingdom. In birds and mammals, gastrulation is a double phasic process: the first phase--entoderm individualization by means of delamination (in combination with immigration), double layer germ formation; the second phase--individualization of mesoderm and chorda from the epiblast composition, a triple layer germ formation, the axial complex germs formation. During phylogenesis of the animal kingdom not only means and mechanisms of gastrulation change but also the contents of the process. For example, in Chordata besides increase in number of germ layers, gastrulation also includes the formation of the axial germ complex. As a result of gastrulational rearrangements of the blastula cellular maternal, the gastrula cell complex (germ layers and germs) come into a new system of interrelationships owing to which architectonic organizational bases of each particular animal type is laid down.


[Morphologic and histochemical characteristics of mammalian embryos during the pre-implantation period of development]. Submicroscopic embryo organization during preimplantation development was analyzed and its carbohydrate metabolism at these stages was studied. In the process of investigation the following regularities were revealed: progressive rearrangement of the nucleus (from compact to reticular); alterations in cytoplasmic structures (in multivesicular bodies, in autophagal vacuoles, in mitochondria, in granular cytoplasmic network, in lamellar structures); complication of intracellular interrelations (by means of microvilli and median bodies at early stages and during subsequent formation of cellular processes, contacts after "thorn--net" pattern, dense, fissure-like contacts and desmosomes). By means of cytochemical and electron histochemical methods, glycogen distribution in embryos at different stages of development was elucidated, and tendency to its decrease with the progress of the development was noted, with its least contents being at the stage of blastocyst.


[Reciprocal homology of the preotic mesodermal segments of representatives of different classes of vertebrates]. The data of the literature and those of the author on the origin of preotic mesodermal segments are discussed. Only in Cyclostomata all preotic segments are formed from the wall of archenteron and are larval segments. In all the gnathos tomata, the primary gastral segments are substituted, to different degrees, by postlarval peristonal mesoderm. The preotic mesomeres of Cyclostomata are homologous to II--IV mesomeres of Branchiostoma lanceolata. The anterior cephalic cavity and the premandibular segment of the elasmobranchia are homologous to I and II segments of Branchiostoma lanceolata. The mandibular mesoderm of the elasmobranchia includes the gastral mesoderm (homologous to III and some subsequent segments of Brachiostoma lanceolata) and peristomal mesoderm. The mandibular mesoderm in higher vertebrates has the same composition, but their anterior larval segments disappear and are substituted by gastral part of the mandibular mesoderm.


[Ultrastructural analysis of reactive changes in the exo- and endocrine epithelium of embryonal pancreas in organ cultures]. The purpose of the work was to study reactive changes of endocrine and exocrine epithelii of the rat embryonic pancreas in organic culturation. The culturation was carried out at 34 degrees C and in the nutritional mixture of the following composition: medium 199--70%, cattle serum--20%, chicken embryo extract--10%, glucose--400 mg/100 ml, vitamin "C"--7 mg/100 ml, benzilpenicillin--50 U/ml. Three series of experiments were carried out with cultivation of the pancreatic gland of 18, 19 and 20-day-old embryos for 4--28 days. The electronograms obtained demonstrate a certain difference in reactivity, cytophysiology and differentiation of exocrine and endocrine epithelium under the conditions of organic cultivation. During the process, endocrine epithelium undergoes primary differentiation, secondary cytodifferentiation and, further, degenerative changes and necrosis develop. B-cells of the insular apparatus grow and function better than the exogenous epithelium. On the 28th day of cultivation, the embryonic pancreas of 19-day-old embryo demonstrates certain signs of synthesis and B-granule formation. In B-cells cytoplasm, granules of different stages of secrete formation are revealed.


[Sutureless anastomoses in gastrointestinal surgery with and without steady magnetic field (experimental study)]. Experimentally in 52 dogs, sutureless gastro-duodenal and ceco-jejunal side-to-side anastomoses were done by means of devices proposed by N.N. Kanshin for connecting void organs, and the features of accretion of the organ walls under the effect of both simple mechanical compression and that with the help of a steady magnetic field were studied. In both variants the process of anastomosis formation completes at 6-7 days after the operation and natural elimination of the compressing elements occurs at 7-8 days. Morphological examinations of sutureless anastomoses formed under a magnetic field or without it revealed no differences between them. The experimental results demonstrated a number of significant advantages of the sutureless methods of tissue connection over the traditional manual intestinal suture.


Bupivacaine anesthesia in retinal detachment surgery. Retinal detachment surgery and other long-duration ocular procedures can be performed safely with local anesthesia, but a long-acting anesthetic is required. A randomized and masked prospective series of 126 scleral buckling procedures was undertaken to test a mixture of bupivacaine (Marcaine), lidocaine (Xylocaine), and epinephrine against lidocaine and epinephrine. The data collected show a conclusive superiority of the bupivacaine mixture in longevity of action and overall performance. Also, there was significantly less variability in the quality of anesthesia with the mixture than with lidocaine (p = .0015).


Antibodies in the intestinal secretions of rats. Primary and secondary responses to polymeric flagellin. The antibody responses in serum and secretions obtained from the mucosal surfaces of the small intestine of rats immunized by a parenteral and intestinal route have been compared. Though no significant differences in the mean serum titres were found, the responses of animals immunized via the latter route to large doses of antigen were far less uniform. Apart from the first few days of the primary response, antibody activity was found in three major immunoglobulin classes (IgG2, IgA and IgM), irrespective of the route of immunization. Significant antibody activity appeared in the intestinal surface secretions only after two injections of antigen. In rats immunized parenterally the activity was found only in the IgG2 component. Whilst activity was found in both  IgG2 and IgA fractions of the secretions obtained from intestinally immunized rats, it was predominantly of the IgG2 class. The possible significance of this observation is discussed.


Effects of changes in Mg++ ion concentration upon bacterial inhibition by beta-2-thienylalanine in defined media. Variation in the inhibition of growth of Escherichia coli and Shigella sp. in various media containing beta-2-thienylalanine was attributed to differences in concentrations of Mg++ ions. Random blood samples 112 infants were tested for elevated phenylalanine in the phenylketonuria (PKU) screening assay. Magnesium ion levels also affected the results of this assay. At 0.05 g/1 MgSO4, the concentration present in commerical PKU test agar, four false positives were detected, while no readings could be made due to overgrowth of the Bacillus subtilis test strain when the concentration was increased to 0.1 g/1.


Effects of anti-rheumatic drugs on immunological parameters. A short review is presented of the immune and inflammatory sites of action of the more common agents in use by rheumatologists--in particular, corticosteroids, the non-steroidal anti-inflammatory and immunosuppressive drugs.


Scleroderma: pathogenic factors and current management. The aetiology of scleroderma remains unknown. Pathogenetic mechanisms may originate from vascular, collagen or immune abnormalities. These are reviewed and the current management although in the main unsatisfactory may alleviate a number of the distressing symptoms.


The role of calcium ions in the regulation of rat thymocyte pyruvate oxidation by mitogens. 1. Calcium concentrations in the nanomolar range cause a specific stimulation of the oxidation of pyruvate by isolated mitochondria from rat thymus that is sufficient to account precisely for the stimulation of pyruvate oxidation observed when rat thymocytes are incubated with the mitogens concanavalin A or ionophore A23187. 2. Higher concentrations of Ca2+ (more than 50 nM) inhibit the oxidation of NAD+-linked substrates by rat thymus mitochondria without affecting the oxidation of succinate or ascorbate+ NNN'N'-tetramethyl-p-phenylendiamine. 3. The addition of Ni2+ or Co2+ (2mM) to rat thymocytes prevents the response to concanavalin A at the level of pyruvate oxidation without affecting the stimulation of glycolysis induced by this mitogen. In contrast, the complete metabolic response to the ionophore A23187 is abolished by these ions. Ni2+ and Co2+ interfere with the ability of the ionophore to transport Ca2+ across the plasma membrane. 4. Concanavalin A, but not ionophore A23187, increases the respiratory inhibition induced by Ni2+ and Co2+. 5. These results support the view that mitogens stimulate lymphocyte pyruvate oxidation through an increase in cellular Ca2+ uptake.


The location of purine phosphoribosyltransferase activities in Escherichia coli. During the preparation of spheroplasts, adenine phosphoribosyltransferase (EC 2.4.2.7) and hypoxanthine phosphoribosyltransferase (EC 2.4.2.8) were released in parallel with cytidine deaminase (EC 3.5.4.5) and uridine phosphorylase (EC 2.4.2.3), which, on other evidence, are considered to be located intracellularly. The two phosphoribosyltransferases and uridine phosphorylase were not significantly associated with purified membrane fractions as was purine nucleoside phosphorylase (EC 2.4.2.1). The effects of the poorly permeable enzyme-inactivating reagents, 4-diazoniumbenzenesulphonate, 7-diazonium-1,3-naphthalene-disulphonate and 2,4,6-trinitrobenzenesulphonate, on Escherichia coli indicate that all the above-mentioned enzymes and also the xanthine-guanine phosphoribosyltransferase [Miller, Ramsey, Krenitsky & Elion (1972) Biochemistry 11, 4723--4731] are located intracellularly.


Protection of the pancreatic beta-cell glucoreceptor mechanism for insulin secretion during culture in chemically defined medium. High concentrations of glucose have a protective effect on the glucoreceptor mechanism for insulin secretion during culture of pancreatic islets in chemically defined media. To study at what level glucose exerts this effect, insulin secretion from beta-cell-rich mouse pancreatic islets was measured before and after culture for 1 week in the presence of different substances. Before culture, glucose and inosine were potent stimulators, mannose and fructose were less potent and xylitol had no effect on secretion. Culture in 3mm-glucose resulted in a 10-fold decrease in the insulin response to glucose stimulation. A less marked decrease was noted after culture in 20mm- or 30mm-glucose. Inosine-stimulated secretion was much decreased after culture in high concentrations of glucose, whereas the responses to mannose or fructose were unchanged. After culture in 30mm-mannose, glucose-stimulated secretion was similar to that observed after culture in high concentrations of glucose, whereas the response to mannose had much decreased. There were no secretory responses to glucose or fructose after culture in 30mm-fructose, or to glucose or xylitol after culture in 30mm-xylitol. Culture in 10mm-inosine did not preserve any significant response to glucose or inosine. The insulin contents of islets and culture media were higher after culture in high concentrations of glucose, mannose or inosine than after culture in fructose, xylitol or low concentrations of glucose. It is suggested that glucose, and to some extent mannose, preserves the glucoreceptor mechanism for insulin secretion by influencing an early stage in glucose metabolism, presumably glucokinase activity.


The stimulus-secretion coupling of glucose-induced insulin release. Effect of exogenous pyruvate on islet function. 1. In isolated pancreatic islets, pyruvate causes a shift to the left of the sigmoidal curve relating the rate of insulin release to the ambient glucose concentration. The magnitude of this effect is related to the concentration of pyruvate (5--90 mM) and, at a 30 mM concentration, is equivalent to that evoked by 2 mM-glucose. Pyruvate also enhances insulin release in the presence of fructose, leucine and 4-methyl-2-oxopentanoate. 2. In the presence of glucose 8 mM), the secretory response to pyruvate is an immediate process, displaying a biphasic pattern. 3. The insulinotropic action of pyruvate coincides with an inhibition of 45Ca efflux and a stimulation of 45Ca net uptake. The relationship between 45Ca uptake and insulin release displays its usual pattern in the presence of pyruvate. 4. Exogenous pyruvate rapidly accumulates in the islets in amounts close to those derived from the metabolism of glucose. The oxidation of [2-14C]pyruvate represents 64% of the rate of [1-14C]pyruvate decarboxylation and, at a 30 mM concentration, is comparable with that of 8 mM-[U-14C]glucose. 5. When corrected for the conversion of pyruvate into lactate, the oxidation of 30 mM-pyruvate corresponds to a net generation of about 314 pmol of reducing equivalents/120 min per islet. 6. Pyruvate does not affect the rate of glycolysis, but inhibits the oxidation of glucose. Glucose does not affect pyruvate oxidation. 7. Pyruvate (30 mM) does not affect the concentration of ATP, ADP and AMP in the islet cells. 8. Pyruvate (30 mM) increases the concentration of reduced nicotinamide nucleotides in the presence but not in the absence of glucose. A close correlation is seen between the concentration of reduced nicotinamide nucleotides and the net uptake of 45Ca. Menadione inhibits the effect of pyruvate on insulin release, without altering its rate of oxidation. 9. Pyruvate, like glucose, modestly stimulates lipogenesis. 10. Pyruvate, in contrast with glucose, markedly inhibits the oxidation of endogenous nutrients. The latter effect accounts for the apparent discrepancy between the rate of pyruvate oxidation and the magnitude of its insulinotropic action. 11. Dichloroacetate fails to affect glucose oxidation and glucose-stimulated insulin release. 12. It is concluded that the effect of pyruvate to stimulate insulin release depends on its ability to increase the concentration of reduced nicotinamide nucleotides in the islet cells.


Inhibition of isoleucyl-transfer ribonucleic acid synthetase in Escherichia coli by pseudomonic acid. The mode of action of the antibiotic pseudomonic acid has been studied in Escherichia coli. Pseudomonic acid strongly inhibits protein and RNA synthesis in vivo. The antibiotic had no effect on highly purified DNA-dependent RNA polymerase and showed only a weak inhibitory effect on a poly(U)-directed polyphenylalanine-forming ribosomal preparation. Chloramphenicol reversed inhibition of RNA synthesis in vivo. Pseudomonic acid had little effect on RNA synthesis in a regulatory mutant, E. coli B AS19 RC(rel), whereas protein synthesis was strongly inhibited. In pseudomonic acid-treated cells, increased concentrations of ppGpp, pppGpp and ATP were observed, but the GTP pool size decreased, suggesting that inhibition of RNA synthesis is a consequence of the stringent control mechanism imposed by pseudomonic acid-induced deprivation of an amino acid. Of the 20 common amino acids, only isoleucine reversed the inhibitory effect in vivo. The antibiotic was found to be a powerful inhibitor of isoleucyl-tRNA synthetase both in vivo and in vitro. Of seven other tRNA synthetases assayed, only a weak inhibitory effect on phenylalanyl-tRNA synthetase was observed; this presumably accounted for the weak effect on polyphenylalanine formation in a ribosomal preparation. Pseudomonic acid also significantly de-repressed threonine deaminase and transaminase B activity, but not dihydroxyacid dehydratase (isoleucine-biosynthetic enzymes) by decreasing the supply of aminoacylated tRNA(Ile). Pseudomonic acid is the second naturally occurring inhibitor of bacterial isoleucyl-tRNA synthetase to be discovered, furanomycin being the first.


Stimulation of proinsulin biosynthesis and insulin release by pyruvate and lactate. Increasing concentrations of pyruvate failed to stimulate proinsulin biosynthesis and insulin release in freshly isolated islets. Glycolytic flux (3H2O from [5-3H]glucose) decreased by 80-85%, but decarboxylation of [1(-14)C]pyruvate was unaffected in islets tested immediately after alloxan exposure. This strongly suggested that in freshly isolated islets, beta-cells, in relation to other islet cells, hardly contribute to the decarboxylation of pyruvate. Non-alloxan-treated cultured islets decarboxylated 2-2.5 times as much pyruvate as did alloxan-treated islets cultured for 15-18h. Thus the contribution of beta-cells to the metabolism of pyruvate after culturing markedly increased. Concomitantly beta-cells became responsive to pyruvate. At 20mM-pyruvate, release of prelabelled proinsulin and insulin and incorporation of [3H]leucine into proinsulin reached values approximately half of those obtained with 20mM-glucose. Lactate was as effective as pyruvate in inducing responses in cultured islets. The experiments indicate that a critical degree of substrate utilization is necessary for the generation of signals for insulin release and proinsulin biosynthesis.


Tgamma cells in systemic lupus erythematosus. Variation with disease activity. Circulating T cells bearing receptors for the Fc portion of IgG (T gamma) were identified by sensitive immunofluorescent techniques with rabbit IgG b4 allotype/anti-b4 complexes. A twofold decrease in both proportion and absolute number of T gamma cells was found in patients with active systemic lupus erythematosus (SLE) relative to values obtained during disease remission. The reduction in T gamma cells was most evident in patients with severe hypocomplementemia. A deficit of T gamma cells in active patients was not demonstrated. The percentage of total T cells rosetting with sheep erythrocytes was reduced in peripheral blood of most patients regardless of disease activity status, but particularly during SLE exacerbation. Cells lacking intrinsic surface immunoglobulin, IgG Fc receptors, and receptors for sheep erythrocytes were increased. These cells, operationally termed null, exhibited an inverse linear relationship with T cells that was not apparent in regression analyses performed against other lymphocyte subpopulations. Such differences were not found for B cells and IgG receptor-bearing non-B/non-T cells which were present in normal proportions in virtually all patients. The origin and functional significance of these unusual lymphocyte subpopulation abnormalities are discussed.


Histologic assessment of lymphokine-mediated suppression of chondrocyte glycosaminoglycan synthesis. An experimental model has been developed to histologically assess the effect of T cell mitogen-induced lymphokines derived from rabbit splenocytes on proteoglycan matrix depleted auricular cartilage explant glycosaminoglycan synthesis. Explant exposure to lymphokine was shown by light and electron microscopy to significantly suppress chondrocyte glycosaminoglycan regenerative capacity. This inhibitory effect was reversible in that synthetic activity could be restored by placement of explants in control media after as long as 12 days of lymphokine exposure.


Lymphocytes from synovial tissue of a boy with X-linked hypogammaglobulinemia and chronic polyarthritis. Lymphocytes were eluted from synovial tissue of a boy with X-linked hypogammaglobulinemia and chronic polyarthritis. The cell suspension contained 53% lymphocytes and 28% peroxidase-positive, macrophagelike cells, No B lymphocytes, 83% T lymphocytes, and 10% Fc-receptor-bearing lymphocytes were detected. Lymphocyte transformation was induced by polyclonal mitogens (phytohemagglutinin and pokeweed mitogen) whereas no response to antigens (purified protein derivative and Candida albicans antigen) was obtained. The eluted cells displayed antibody-dependent cytotoxicity.


Photodynamic effect of 3,4-benzpyrene on thermo-sensitive mutants of Escherichia coli B. Results obtained with thermo-sensitive mutants of Escherichia coli B have shown that the presence of a protein with impaired structure may be responsible for enhanced sensitivity to the lethal photodynamic effect of 3,4-benzpyrene. Thus, the evidence has been obtained of the in vivo action of excited 3,4-benzpyrene on proteins.


[Treatment with antilymphocyte globulin (ALG) and evolution of renal transplant: observations of 42 cases]. 42 necrokidney transplants, performed in Renal Unit of "Niguarda - Ca' Granda" Hospital in Milan, since 1972, have been examined. Hystocompatibility score and previous transfusions and/or pregnancies apparently did not correlate with three months transplants survival. Our patients have been separated into two groups according to treatment with or without ALG: the group treated with ALG showed a better percentage survival of the kidney at three months a lower incidence of rejection episodes during the same period. The usefulness of ALG treatment is reaffirmed; we consider that a better prognosis at three months probably means a more favorable clinical course.


An immunofluorescence blocking test to detect antibodies against the hepatitis B delta and core (HBcAg) antigens. An immunofluorescence (IFL) blocking test has been developed to detect antibodies against the hepatitis B delta and core (HBcAg) antigens. The test proved useful to overcome the difficulties inherent in the detection of anti-delta by standard direct and indirect IFL procedures and provided a simple alternative to detect anti-HBc whenever serological techniques or indirect IFL, requiring purification of Dane particle cores or rare and selected HBcAg positive substrates, cannot be accomplished. The blocking test proved reliable and specific; though less sensitive than standard IFL techniques, it is simple and valuable in routine serological screening for anti-delta and anti-HBc.


Antilymphocyte antibodies in rheumatoid arthritis. The presence of cold and non-cold reacting antilymphocyte antibodies of IgG class, active against allogeneic T lymphocytes deprived of Fcgamma receptor bearing cells, was investigated by indirect immunofluorescence (IF) and by microlymphocytotoxicity in 50 patients with Rheumatoid Arthritis (RA). 6/50 rheumatoid sera have shown the presence of anti-T-lymphocyte antibodies against 8/50 positivities found when the whole lymphocyte population was employed as the target in IF test. The positive sera were also examined by microlymphocytotoxicity test and the correlation with the number of lymphoid cells in peripheral blood was studied. In only one case (RA + Sjögren's syndrome) a positive IF test, in vitro cytotoxicity and in vivo lymphopenia were observed. In the other IF positive cases neither lymphopenia in vivo nor lymphocytotoxicity of the sera were observed; these results can be due to either the presence of cold or not complement fixing antilymphocyte antibodies.


Salicylates and homoeopathy in rheumatoid arthritis: preliminary observations. This paper reports the results of a pilot study in which 41 patients with rheumatoid arthritis were treated with high doses of salicylate, 3.9 g per day, and the results compared with a further 54 similar patients treated with homoeopathy. Both groups were compared with 100 patients who received placebo. 2 The patients who received homoeopathy did better than those who received salicylate. The design of the trial was such, however, that it was not possible to distinguish between the effects due to the physicians and the effects due to the drugs and a further trial is planned to elucidate this point. 3 Patients on homoeopathic treatment did not experience toxic effects.


The electrocardiogram in the assessment of the effect of drugs on cardiac arrhythmias. The search for the ideal antiarrhythmic drug continues since none of the available agents offers optimum antiarrhythmic therapy. The continuing search coupled with the interest in the mechanisms of cardiac arrhythmias has led to the development of new techniques for the study of arrhythmias and antiarrhythmic drugs. In this article it is proposed to discuss the electrocardiographic methods used in the assessment of antiarrhythmic drugs. Firstly, to discuss the electrocardiogram in the assessment of the clinical electrophysiological properties of a drug and secondly, the electrocardiogram in the assessment of the value of the drug in the management of cardiac arrhythmias in man.


Plasma protein binding interaction between phenytoin and valproic acid in vitro. 1 Valproic acid or phenytoin were added to fresh human serum in varying concentrations and their binding characteristics determined by the method of Scatchard (1949). 2 Changes in serum albumin binding were investigated for phenytoin in the presence of 280, 560, 1050 and 2100 mumol l-1 valproic acid, and for valproic acid in the presence of 40, 120, 280 and 480 mumol l-1 phenytoin. 3 Phenytoin appeared to bind to a single site on the albumin molecule and could be competitively displaced from this site by concentrations of valproic acid above 280 mumol l-1. 4 At high concentrations of valproic acid, the affinity of phenytoin for albumin was greatly decreased but the number of available binding sites was increased from one to four. 5 Valproic acid was bound to two high affinity and five low affinity binding sites but the latter were not detectable at valproic acid concentrations below 2100 mumol l-1. 6 Phenytoin displaced valproic acid from its high affinity binding sites, although this was statistically significant only at a concentration of 480 mumol l-1 phenytoin.


Mechanism of inhibition of tumour growth by aspirin and indomethacin. The growth of a 3-methylcholanthrene-induced fibrosarcoma of C3H mice was inhibited by aspirin and indomethacin. While the tumour contained relatively high concentrations of PGE2-like material, that were markedly diminished by indomethacin treatment, our results did not confirm the recently proposed hypothesis that the anti-tumour effect arises from a restoration of depressed immune function. For example, mice that had completely eliminated their tumours under indomethacin administration were not immune to rechallenge. The tumour-bearing animals were not non-specifically immunodepressed, as their splenic PFC responses against SRBC were enhanced. However, while indomethacin augmented the PFC response in normal mice, this adjuvant effect was depressed in tumour-bearing animals. The spleen-cell PHA responses of tumour bearers were severely depressed, and such cells suppressed the PHA response of normal cells. Only after prolonged indomethacin treatment did animals (with comparable tumour burdens) show weak PHA responses and somewhat diminished suppressive activity. Possible alternative mechanisms, such as direct cytotoxicity, or inhibition of inflammation, phosphodiesterase activity, blood coagulation or calcium availability were not implicated (nor definitively excluded) in the anti-tumour effect.


Chemotherapy of acute myeloid leukaemia in adults: Medical Research Council. Two hundred and fifty patients with acute myeloid leukaemia (AML) were randomized between 2 regimens of chemotherapy: TRAP and BARTS III. Overall, patients randomized to TRAP, which was the more intensive of the 2 regimens, fared slightly better (P = 0.06) than those on BARTS III. However, the improvement in survival associated with more intensive chemotherapy was substantial only for patients who had favourable prognostic features at presentation, such as a normal total leucocyte count, or absence of palpable liver, or, especially, age under 40. Indeed, for patients under 40, those allocated to the more intensive regimen (TRAP) lived considerably longer than those allocated to BARTS III (P less than 0.002) while for patients over 40 there was no material difference in survival between patients on the 2 protocols. It thus appears that intensive chemotherapy is likely to be more effective when favourable prognostic features are recorded.


Bromhexine in severe asthma.

Bromhexine in severe asthma. Fourteen patients with acute severe asthma necessitating hospital admission were all treated with a standard therapeutic regimen, and in addition received either bromhexine or placebo (initially intravenously and subsequently orally) double-blind. We were unable to show any significant improvement in the rate of recovery of the bromhexine-treated group, in terms of either arterial blood gases or change in peak expiratory flow rates.


The effects of oral propranolol and metoprolol on lung function and exercise performance in chronic airways obstruction. Fifteen men with chronic airways obstruction received a test dose of propranol 20 mg orally. Six developed increased breathlessness. Nine who tolerated the test dose received metoprolol (100 mg) and propranolol (80 mg) on different days in a randomized double-blind fashion. Changes in resting and exercise heart rate, spirometry and exercise tolerance were measured 1 and 6 hours later. The drugs had similar effects on heart rate. Propranolol, but not metoprolol, caused significant reduction in forced expiratory volume in one second (FEV1) and peak expiratory flow rate. Neither drug produced significant changes in forced vital capacity (FVC) or exercise performances in the group as a whole, although the range of changes was wide. Despite considerable reduction in FEV1 and FVC in some individuals, most reported no increase in symptoms. Changes in exercise tolerance at 1 hour correlated significantly with changes in FVC but not with those in FEV1. It is proposed that changes in FEV1, though of pharmacological interest, may be less relevant clinically than changes in FVC.


Observation of echinocytosis in eight patients: a phase contrast and SEM study. We report eight cases of echinocytosis discovered after screening of stained smears. The presence of echinocytes was exceptional in adults and children but was more frequent in neonates. In all cases we confirmed the presence of abnormal red cells by careful examination of the blood in wet preparations observed in phase contrast and after glutaraldehyde fixation and processing for SEM. No discernible common denominator was found to explain the presence of echinocytes in the blood of our patients. No echinocytogenic factor could be demonstrated in the fresh plasma. Echinocytes appeared quickly in patients who received exchange transfusion or transfusion of normal red cells. By contrast, in vitro incubation in the presence of substrates allowing constant ATP level never resulted in the formation of echinocytes when normal red cells were suspended in patient's plasma.


Sedimentation cytology in central nervous system leukaemia with a new simple apparatus. The clinical usefulness of a newly devised, simple apparatus, the Nishimura fluid sedimentation chamber, is described. The latter consists of an open-ended plastic tube, an absorbent paper with a central hole, and a glass slide which are stuck to each other with double-sided plastic adhesive tape with a central hole of equal size. The chamber is set to allow 0.5 ml of cerebrospinal fluid (CSF) to be absorbed in 15--20 min. The principle of the sedimentation relies on the absorption of the fluid portion into the absorbent paper with the cellular elements sedimented onto the glass slide. Thin stationery paper is used as the absorbent material which controls sedimentation speed and minimizes cellular loss. 190 CSF specimens obtained from 28 patients with acute leukaemia were processed by this method. The results obtained showed that sedimentation using this simple chamber is quite reliable for the recognition of small number of abnormal cells in the CSF producing little or no noticeable cellular damage. This technique may be applied to other clinical situations in which fluid cytology is useful in establishing a diagnosis or in evaluating clinical progress.


Characterization of serum fibrinogen and fibrin fragments produced during disseminated intravascular coagulation. The fibrinogen and fibrin degradation products (FDP) in serum samples taken from nine patients with suspected disseminated intravascular coagulation have been characterized using a method of immunoprecipitation followed by sodium dodecyl sulphate polyacrylamide gel electrophoresis. Aall of the serum samples contained a fragment with the same electrophoretic mobility as fibrinogen fragment X, while the majority also had evidence of fragments with similar mobility to fibrinogen fragments Y and D. In eight of the nine serum samples there was strong evidence of the D-dimer fragment that is released by plasmin lysis of crosslinked fibrin. Also present in all but one of the samples were fragments of higher molecular weight than fibrinogen which were probably soluble, non-clottable, factor XIIIa induced crosslinked derivatives of fibrinogen. These results suggest that during disseminated intravascular coagulation thrombin and activated factor XIII act upon fibrin(ogen) to form complexes that are subsequently lysed by plasmin to produce soluble crosslinked derivatives of fibrin.