Tumors of the bladder in renal transplant patients: report of a case of adenocarcinoma and review of known cases. A case is presented of adenocarcinoma of the bladder in a 36-year-old man who had undergone renal transplantation 4 years previously. Treatment was cystectomy and ileal loop diversion. A review of the known cases of bladder tumors obtained from the literature and from the Human Renal Transplant Registry is discussed. The 8 cases presented include 4 transitional cell carcinomas, 1 squamous cell carcinoma, 1 nephrogenic adenoma and 2 adenocarcinomas. The unusual occurrence of adenocarcinoma in young male subjects is noted.


Urethral pressure profile during the spinal shock stage in man: a preliminary report. The functional state of the proximal urethra in the spinal shock stage in man is not fully understood. We studied patients with spinal cord injuries during spinal shock and found that the urethral pressure profile had a normal configuration, the peak profile pressure increased with bladder filling and phentolamine (10 mg. intravenously) reduced the peak pressure, with empty and full bladders.


Methadyl acetate and methadone. An open comparison. Heroin addicts were recruited for a 14-week open clinical comparison of methadone hydrochloride and methadyl acetate. Patients were randomly assigned to a methadyl acetate clinic in which methadyl acetate was dispensed to patients three times per week or to a methadone clinic in which methadone was dispensed six days per week. No statistically significant differences were observed between groups in retention rates, illicit drug use, employment rates, or arrest rates. The group treated with methadyl acetate had more dropouts in the first seven weeks than the second seven weeks: this pattern was reversed for the methadone-treated group. The differences were significant (P = .01). Spontaneously reported symptoms suggest that induction with methadyl acetate may be a more clinically variable phenomenon than induction with methadone. The reduction of number of clinic visits in the group treated with methadyl acetate was not a source of variance in treatment effectiveness.


Radiotherapy after definitive surgery for breast cancer. (1) Radiotherapy after definitive surgery for breast cancer has not been proved to have a deleterious effect on patient survival. (2) The beneficial effect of radiation therapy is to decrease significantly local recurrences (P less than .001), which are very difficult to control once they develop. (3) In the hands of experienced radiotherapists, the incidence of complications is quite low. (4) Adjuvant chemotherapy effects on the prevention of local recurrence are most encouraging but still experimental and should at this stage be used mainly in study situations. (5) Until more detailed information is obtained, radiation therapy remains the most effective, least toxic method for the control of local disease.


Therapeutic effect of vitamin C. A co-twin control study. Three different dosages of vitamin C, dependent on body weight, were administered to 44 school-aged monozygotic twins for five months using a double-blind, co-twin control study design. The mothers recorded daily observations of cold symptoms, and multiple biochemical, anthropometric, and psychological measurements were made at the beginning and end of the study. Paired comparisons showed no significant overall treatment effect on cold symptoms, but the response was not uniform in all sub-groups. Treated girls in the youngest two groups had significantly shorter and less severe illness episodes, and an effect on severity was also observed in the youngest group of boys. The seven treated twins in the latter group also grew an average of 1.3 cm more than their untreated co-twins during the five-minth period of the study.


The emergency physician and organ donation. The introduction of public funding for treatment of patients with endstage renal disease has greatly increased the number of patients who can benefit from kidney transplantation. The emergency physician should be alert for the type of trauma victim suitable for organ donation. Moreover, it is important that the physician understand the concept of brain death so that the removal of organs can take place as soon as possible. Certain aspects of kidney maintenance can begin before death has been declared but the total care of the patient must remain foremost. Management of the precadaveric organ donor is identical to that of any patient in a life-threatening situation. In the cadaver stage, the main difference is an increase in fluid input. The emergency physician should be aware of state laws regarding brain death and permission from the next of kin to harvest an organ.


Ultrastructural study of human synovial membrane with immunoperoxidase. An ultrastructural immunoperoxidase study of human synovial membrane biopsies performed in 16 patients with rheumatoid synovitis and in 14 control patients showed that: (1) plasma immunoglobulins have an intercellular distribution and seem to diffuse mainly by an intercellular rather than by a transcellular pathway; and (2) there is a difference in the distribution of plasma IgG and IgM. IgG was found in intravascular and extravascular spaces in all biopsies. IgM was found only in intravascular spaces in control biopsies, but in rheumatoid synovitis it was present in both intravascular and extravascular spaces. This difference in distribution may be due to increased vascular permeability in inflammatory synovitis.


Current practice of coronary artery bypass surgery. Results of a national survey. A survey of techniques used in coronary artery bypass graft (CABG) surgery by 400 experienced cardiac surgeons is presented. These surgeons performed 41,000 CABG operations in 1975. A seventy-question survey form was answered by each surgeon on their techniques for cardiopulmonary bypass and myocardial preservation, choice of bypass conduit, and grafting techniques. We found that extracorporeal circulation is almost always used in CABG surgery. A wide divergence of practice exists in the use of left ventricular vents and in methods of myocardial protection during coronary artery grafting. A spectrum of graft suture techniques is employed, the most common being a running double-ended suture anastomosis with the end of the vein initially fixed only at its heel to the coronary artery. Only 23 surgeons (6 per cent) prefer the internal mammary artery (IMA) rather than saphenous vein, when feasible, as the bypass conduit of choice for CABG surgery.


Rhinoscleroma of the lower respiratory tract. Rhinoscleroma is a chronic granulomatous disease of the respiratory tract endemic to Eastern Europe and Central America which is being recognized with increasing frequency in other countries, including the United States. It was initially described as a lesion of the nose and upper respiratory tract, but is now known to involve the larynx, trachea and bronchi as well to cause slowly progressive asphyxia. Eleven cases of rhinoscleroma with varying degrees of involvement of the lower respiratory tract (larynx, trachea and bronchi) are presented. Present day treatment is both medical, consisting primarily of streptomycin and tetracycline, and endoscopic dilatation. Prolonged medication with careful dose control is necessary. Lower respiratory tract involvement should be considered in patients with chronic destructive granulomatous nasal pathology. This should be especially emphasized if they have an Eastern European or Central American background, or have travelled in these areas in which rhinoscleroma is endemic.


The lateral conchal resection otoplasty. A procedure for surgical correction of protruding ears has been utilized in 118 cases. The technique incorporates steps to correct the most common deformities found on preoperative evaluation. The lateral conchal resection com bined with mattress sutures is not complex and thus readily learned by residents. It has yielded consistently excellent cosmetic results combined with an exceedingly low complication rate. The procedure is adaptable to well over 90 percent of patients seeking an otoplasty procedure.


Long-term effect of hbs antigenemia on patient survival after renal transplantation. We studied 121 renal-graft recipients to delineate the effects of HBs antigenemia on patient and graft survival. Grafts had functioned for at least six months; follow-up periods averaged 37 months. Mortality was significantly higher (P less than 0.05) in the HBs Ag-positive (17 deaths among 61 patients) than in the HBs Ag-negative group (eight of 60 patients). Patient and graft survivals, from six months onwards, were significantly lower at four years in the positive (64 and 60 per cent respectively) than in the negative group (87 and 80 per cent respectively). These differences resulted solely from a fivefold increase in mortality from liver disease in the positive group and were unrelated to graft rejection. HBs antigenemia did not improve graft tolerance during the first 24 months in 129 patients in whom repeated HBs Ag determinations had been obtained before operation. We conclude that HBs antigenemia has an unfavorable effect on transplant and patient survival.


Association of graft survival with host response to hepatitis B infection in patients with kidney transplants. We studied the relation of host response to hepatitis B infection before transplantation with survival of kidney grafts in 79 patients receiving 87 transplants. Antibody to hepatitis B surface antigen (anti-HBs) signaled early graft rejection (median survival congruent to two months), whereas hepatitis B surface antigen (HBsAg) signaled delayed rejection (greater than 22 months). Patients with neither HBsAg nor anti-HBs had graft survival times (median congruent to 16 months) similar to the HBsAg carriers but significantly longer than the anti-HBs-positive patients (p less than 0.01). Similar results were observed when patients who received HLA-identical kidneys or had anti-HLA antibodies before transplantation were excluded. The highest probability of graft rejection was in patients with anti-HBs who received kidneys from male donors. The probability that such grafts would survive for four months was less than 20 per cent. HLA-nonidentical kidneys transplanted into patients with anti-HBs have a poor prognosis, whereas such grafts in HBsAg carriers have as good a prognosis as grafts in uninfected recipients.


Watching the monitors: "PAID" prescriptions, fiscal intermediaries and drug-utilization review. Prescription monitoring evolved from the need of drug firms to obtain marketing information. Today, extensive monitoring is also done by fiscal intermediaries who administer prepaid drug benefit plans, both private and governmental, particularly Medicaid. The most important such agent is PAID Prescriptions. Under various contracts, PAID monitors physician, pharmacy, and patient behavior related to prescriptions and uses review processes that evaluate certain kinds of behavior for appropriateness. The criteria of appropriateness are essentially those that save money. PAID negotiates a program fee with the insurer (public or private) and applies constraints so that prescription and administrative costs do not overrun that fee. PAID and other monitors have contemplated expansion into the realm of defining and encouraging appropriate prescribing under the concept of "drugutilization review." The actual practices of PAID, particularly the background of fiscal enforcement, may impede the development of an actual drug-utilization review process.


Follow-up study of male and female offspring of DES-exposed mothers. This follow-up study presents the effects of DES on the genital tract of male and female offspring of mothers who were part of a double-blind, placebo-controlled investigation during 1951 and 1952 aimed at determining the effect of DES on pregnancy. Epididymal cysts, hypotrophic testes, and capsular induration were the more common genital lesions found in 25% of 163 DES-exposed males as compared to 6% in 168 control males. Semen analysis data on 39 subjects of the DES-exposed group and 25 subjects of the control group showed that 26% of the DES-exposed group produced an ejaculate volume under 1.5 ml; no such cases were observed in the control group. The average values for sperm density ant total motile spermatozoa per ejaculate, although in the normal range, were more than two times lower in the DES-exposed group as compared to the controls. A quality score of greater than 10 ("severely pathologic semen") was found in 28% of the DES-exposed group as compared to 0 in the control group. An association of pathologic semen quality with physical abnormalities was found only in the DES-exposed group. Two cases of azoospermia, one without genital abnormalities on physical examination and one with bilateral hypotrophic testes were observed so far in the DES-exposed group. Eighteen percent of 229 DES-exposed female patients had irregular menstrual cycles (oligomenorrhea) as compared to 10% of 136 controls. The history of pregnancy revealed a lower incidence of pregnancy in the DES-exposed group (18%) than in the control group (33%). Circumferential ridges of the vagina and cervix were seen in 40% of 229 DES-exposed females but in none of 136 controls. Colposcopic findings in the vagina revealed adenosis in 66.8% of the DES-exposed females and in 3.6% of the control group. Dysplastic lesions were more prevalent in the vagina and cervix of the DES-exposed subjects. No cases of cancer were observed in either the male or female offspring.


Sex preselection.

Sex preselection. There have been attempts to select the sex of a child prior to conception in both animals and humans. Centrifugation, microelectrophoresis and density gradient sedimentation have been used to separate X and Y sperm in animals. Only the latter technic has produced a change in sex ratio. In the human, timing of coitus or artificial insemination in relation to ovulation has been the popular method for influencing the sex of a child. This review suggests caution in accepting the claims of success for coital timing. Sperm bearing the Y chromosome can now be identified by quinacrine staining. Using this marker, Ericsson showed that when sperm are allowed to swin into columns of liquid albumin a high percentage of Y-bearing sperm are found in the most distal portion of the column. At this time it has not been shown whether the fraction enriched with Y sperm can produce a preponderance of males.


In utero diagnosis of agnathia, microstomia, and synotia. A rare case of the in utero observation of agnathia, microstomia, and synotia associated with hydramnios is presented. The correct diagnosis is made by observing an absent mandible in a patient with hydraminios.


Repair of postextraction sockets: influence of homogeneous bone implants preserved by formaldehyde. An experimental study in dogs. Small bone sticks from a dog, fixed in formaldehyde from 1 to 4 weeks, were used as homoimplants in the left postextraction sockets of dogs, and the right sockets were allowed to heal as ungrafted controls. The animals were killed 5, 11, 22, and 60 days after implantation. No obvious differences were discovered, either clinically or radiographically, between the repair of the control sockets and that of the experimental sockets. However, appreciable histologic differences could be noted. The presence of the implant disturbed and retarded both the organization of the granulation tissue and the process of intra-alveolar ossification. The attempt to use homogeneous bone implants that had been preserved in formaldehyde in order to stimulate osteogenesis in the host produced unsatisfactory results, since it retarded the process of postextraction alveolar repair.


The prophylactic use of propylic ester of p-hydrobenzoic acid on alveolitis sicca dolorosa. A preliminary report. A double-blind experiment was performed to test the possible prophylactic effect of the antifibrinolytically active propylic ester of p-hydroxybenzoic acid (PEPH) on alveolitis sicca dolorosa (dry socket). Tablets containing PEPH or placebo were inserted at random selection into the alveoli of forty-five consecutive patients, each of whom had had an impacted mandibular third molar removed. The prophylactic effect of PEPH in this study was found to be highly significant as compared to that of placebo, and no patients in the experimental group developed alveolitis sicca dolorosa.


Insulin, obesity, and triglyceride interrelationships in sixteen children with familial hypertriglyceridemia. Sixteen children with familial hypertriglyceridemia were studied to determine whether there were any distinctive insulintriglycerid-obesity relationships in pediatric familial hypertriglyceridemia. Eleven of 16 children had calculated fat mass greater than the 97th percentile for age, height, and sex. When compared with 16 normal control subjects matched for degree of obesity immunoreactive insulin and glucose response during oral glucose tolerance was similar for normal and hypertriglyceridemic children. By either simple correlation or multiple regression analysis, plasma, triglycerides did not correlate significantly with measurements of insulin or obesity in hypertriglyceridemic or normal children. Within the limits of a small sample size, and in the presence of obesity, insulin does not appear to play a predominant role in the genesis of hypertriglyceridemia in children with familial hypertriglyceridemia. With a small mean weight loss of 1.8 kg and adherence to a diet with 20% of calories as protein, 40% each as fat and carbohydrate, polyunsaturate to saturate ratio of 1.5:1, mean plasma triglycerides were reduced from 238 to 140 mg/100 ml in the 11 obese children with familial hypertriglyceridemia (P less than 0.02). Speculation In spite of the complicating role of obesity, adolescence, and the small sample size, it is interesting to note that the correlation coefficients between triglyceride and insulin/glucose area (0.36), and insulin area (0.30), although not significant (P less than 0.1), were considerably higher in hypertriglyceridemic children than in normal subjects in whom comparable correlation coefficients were 0.08 and 0.08. This infers that the potential role of insulin in triglyceride metabolism in children with familial hypertriglyceridemia might be discerned with longitudinal follow-up into adulthood.


Management of the burned hand.

Management of the burned hand. Current concepts in the management of acute and chronic injury to hands due to thermal burns are presented. A review of relevant functional anatomy and its alteration by the burn process is outlined. The maintenance of wrist extension, metacarpophalangeal flexion, and an open thumb web is critical in the acute phase. The physical therapist, using splints and regular exercise, is the key person in maintaining this position. The use of antibacterial agents, surgical debridement, and skin grafting is discussed. Surgical methods of reconstruction in chronic burns, the long-term role of the physical therapist, and the use of compression garments to minimize scar are stressed.


Reconstruction of the breast after mastectomy. We have described our techniques for reconstruction of the breast after a simple mastectomy, a modified radical mastectomy, and a radical mastectomy. Inadequate skin cover must be relieved, preferably by transposition of a thoracoepigastric flap. Not only must a mound be created, but also a nipple-areola complex. The areola can be constructed by nipple-sharing techniques from the opposite breast or by the use of the labia minora and/or the labia majora. However, we advise preservation and banking of the nipple-areola (or areola) by the ablative surgeon, when possible. The remaining breast usually requires some modification to match the reconstructed one.


Use of the united suture in microvascular anastomoses. A technique for microvascular anastomoses is described. It leaves one suture united until the last, a maneuver which helps to avoid picking up the posterior wall with the anterior wall.


Experimental study of tissue response to ruptured gel-filled mammary prostheses. Miniature "soft gel" filled breast prostheses were implanted into rats, and half of these were purposefully ruptured upon insertion. At sacrifice of the animals later, the position of the exuded gel, the variability of the capsule thickness, and the extent of the capsule formation were evaluated. The capsule thickness was significantly increased around the ruptured prostheses, in response to the exuded gel. Also, the gel migrated through the fibrous capsule and into the surrounding tissue, eliciting an inflammatory response there to produce capsule thickening.


The closure of defects by using adjacent triangular flaps with subcutaneous pedicles. Triangular flaps with subcutaneous pedicles have been consistently reliable for closing many defects in our 12-year experience. Before, we used mainly the lateral subcutaneous pedicles, but now we tend to use central pedicles. One can also leave partial skin bridges in the pedicles to prevent circular scar patterns, where the latter are undesirable.


Two-point discrimination distances in the normal hand and forearm: application to various methods of fingertip reconstruction. Two-point discrimination in the hand and forearm is best during the third decade of life. In the fingertips, the ulnar digits are more discriminating than the radial digits. Males and females have equal two-point discrimination during each age decade. Fingertips are twice as discriminating as the thenar and hypothenar areas, and the thenar and hypothenar areas are twice as discriminating as the volar side of the wrist; the wrist is twice as discriminating as the forearm. The Kleinert and Kutler flaps demonstrated the best two-point discrimination among the repaired fingertips.


Lymphedema of the penis.

Lymphedema of the penis. Lymphangiectomy with primary closure or skin grafting appears to be the treatment of choice for lymphedema of the penis. The method offers good cosmetic and functional results.


Closure of skin defects near the proximal interphalangeal joint--with special reference to the patterns of finger circulation. In dealing with skin losses of the proximal segments of the finger, one must be mindful of the vessel arrangements. Preservation of the axial vessels removes the usual restrictions of length to breadth ratios which apply to flaps planned on a random pattern arrangement.


Studies on the pigmentation of skin grafts: the ultrastructure of epidermal melanoxytes. We carried out ultrastructural studies on the epidermal melanocytes in human skin autografts, before and after transplantation. On comparing the results with those described in our previous paper, the present findings are in accord with those light microscope findings. As we suggested earlier, the degree of pigmentation in a skin graft is probably due not only to quantitative changes in the transfer and formation of melanosomes, but also to the distribution, the degradation pattern, and the size of the melanosomes within the keratinocytes. Rupture of lysosomes, as a consequence of transplantation, may also contribute to the pigmentation of the skin graft.


Tris(2,3-dibromopropyl) phosphate: mutagenicity of a widely used flame retardant. Tris(2,3-dibromopropyl) phosphate, a widely used flame-retardant additive for textiles, is mutagenic to histidine-requiring strains of Salmonella typhimurium. Extracts of fabrics treated with this compound are also capable of inducing mutations in these bacterial strains.


Nucleotide sequences from the rabbit beta globin gene inserted into Escherichia coli plasmids. A 169-nucleotide region from the rabbit beta globin gene has been sequenced by analysis of complementary DNA's cloned in bacterial plasmids. Comparison of these sequences with those established for this gene by other techniques provides evidence of a high degree of fidelity and allows the unambiguous establishment that these plasmids do not contain harmful sequences.


Novel screening procedure for recombinant plasmids. Lysed bacterial colonies containing potential recombinant plasmids were mixed with molten agar and sealed into slots of an agarose gel. After electrophoresis overnight, the gel was stained with ethidium bromide, which clearly reveals recombinant plasmids. Xenopus laevis ribosomal DNA and histone DNA of Psammechinus miliaris were ligated into pCRI plasmids and screened by this method.


Plasmid detection and sizing in single colony lysates. A simple and contained procedure for the rapid assay of the presence and size of plasmids similar to Col El is described. Bacteria are picked from an agar plate with a toothpick, lysed with dodecyl sulfate and heat, and placed directly on an agarose gel for electrophoresis.


Septic pulmonary embolization.

Septic pulmonary embolization. Septic pulmonary embolization occurs when an infected thrombus lodges in the pulmonary arterial tree. Pulmonary abscess, empyema, bronchopleural fistula, shock and death may follow. During the preantibiotic era, septic pulmonary embolization was a dread complication of septic thrombophlebitis occurring in the pelvis and after infections of the head and neck. More recently, the multiplicity of long term indwelling catheters has changed the epidemiologic aspect of this disease, pointing toward iatrogenic causes in many instances. The drug addict, however, remains the person at greatest risk of having septic pulmonary embolization develop. A clinical evaluation seeking drug abuse and related stigmata is extremely helpful in suggesting the proper cause, establishing the presence of right-sided endocarditis and directing appropriate therapy. Staphylococcus aureus is the most common offending organism in all patient populations except for the patient with thermal injury in which gram-negative organisms predominate. Early diagnosis and proper therapy, which includes high doses of parenteral antibiotics and control of the inciting septic focus in all instances, are prerequisites for a favorable outcome.


Body water distribution after operation. The effect of a major surgical procedure on the distribution of body water was investigated in two groups of patients. The first group of four patients did not receive any salt during the first 24 hours following operation, while the second group of five patients received a moderate amount of isotoric saline solution during this period. For seven days prior to operation, the patients were maintained by bed rest and a daily intake of 100 milliequivalents of sodium and 100 milliequivalents of potassium. A multiple isotope dilution technique was used, before and after operation, to measure red cell mass, plasma volume, extracellular water, total body water and total exchangeable sodium. In addition, the aldosterone secretion rate was measured, both before and after operation, to assess the physiologic control of the extracellular water volume. In the patients who did not receive any salt, the mean extracellular water volume decreased following operation from 39.7 to 37.5 per cent of the total body water; a mean decrease of 0.9 liter while the aldosterone secretion rate increased significantly, p less than 0.02, by 101 per cent from 206 to 414 micrograms per day. In the second group of patients who received an average of 1.3 liters of isotonic saline solution during the first 24 postoperative hours, the extracellular water increased from 37.9 to 42.8 per cent of total body water; a mean increase of 1.1 liters p less than 0.02. The mean aldosterone secretion rate in this group of patients increased by only 13 per cent from 167 to 188 micrograms per day. The blood volume did not change in either group as a result of operation. These data support the hypothesis that, following operation, sequestration of extracellular water occurs within the injured tissues, necessitating the postoperative infusion of a moderate amount of a balanced salt solution.


Effects of intravenous bolus dosages of methylprednisolone and local radiation on renal allograft rejection and patient mortality. One hundred and thirty of 179 rejection episodes encountered in 205 transplants were reversed by treatment with a bolus preparation of methylprednisolone. Ninety-six of these episodes also required an increase in oral prednisone dosage. No beneficial effect on over-all graft survival was noted, but a significant rise in the mortality, secondary to sepsis, was noted in those who received more than 5 grams of methylprednisolone. Local radiation to the graft did not contribute to better graft survival or mortality.


Lower urinary tract pharmacology. I. Anatomic considerations. With this issue Dr. Bissada, Dr. Finkbeiner, and Dr. Welch introduce a series on uropharmacology, starting with the lower urinary tract. Since an understanding of the anatomy, neurophysiology, and basic pharmacology is necessary, Part I is a description of the functional anatomy of the lower urinary tract and the mechanisms of continence and voiding. Part II is a review of the differences between somatic and autonomic reflexes; the afferent and efferent innervation of lower urinary tract; the organization of pelvic ganglionic cells and the spinal and supraspinal control of lower urinary tract function. Subsequent articles will be on basic pharmacology of lower urinary tract and individual drug classes.


Renal rupture after transplantation.

Renal rupture after transplantation. Nine instances of spontaneous allograft rupture have been identified in a series of 325 renal transplantations. Repair of the graft was accomplished in 4 cases. One graft functioned for five and one-half years, one kidney was removed immediately because of uncontrolled hemorrhage, and two grafts were subsequently removed because of rejection. Immediate nephrectomy was performed in 5 cases of irreversible rejection. The duration of ischemia and method of preservation appeared to have no etiologic importance. Evidence of severe acute rejection was present in all 9 cases. The recent increase in graft rupture parallels the increasing frequency of severe early acute rejection reactions.


The effect of epinephrine and isoproterenol on insulin secretion and glucose utilization in isolated islets of Langerhans from mice. The effect of epinephrine and isoproterenol in different concentrations and adrenergic blocking agents on glucose induced insulin secretion and glucose utilization was studied in isolated islets of Langerhans from mice. Epinephrine in physiological concentrations significantly inhibited the glucose induced insulin secretion. This effect was not mediated by a change in glucose utilization but involved alpha-adrenergic stimulation. Isoproterenol significantly stimulated the glucose induced insulin secretion but had no effect on glucose utilization. Beta-adrenergic stimulation by isoproterenol at low glucose concentration was not sufficient to stimulate insulin secretion. The results are discussed in relation to current therories on the mechanism of glucose induced insulin secretion.


Cell-mediated immunity and its role in resistance to infection. The recently acquired knowledge of the importance of cell-mediated immunity in many illnesses and the discovery of a variety of substances that can restore certain cell-mediated immune functions has served to focus the attention of physicians on this area of immunity. It is important for practicing physicians to have a clear understanding of current knowledge of the role of cell-mediated immunity in resistance to infection and how this arm of the immune system relates to the diagnosis and therapy of infectious diseases.


Seasonal incidence of some congenital malformations in the central nervous system in Sweden, 1965-1972. Seasonal trends of some congenital CNS malformations in infants born in Sweden during the years 1965 to 1972 were investigated. The study is based on reports to the Swedish Register of Congenital Malformations, statistics from the National Board of Health, and records from Malmö General Hospital and the Hospital of Lund. The malformations analysed in this study are anencephaly, spina bifida aperta (with or without hydrocephalus) and isolated hydrocephalus. Variations in incidence of months of birth and last menstrual period (LMP) were tested statistically in three different ways: standard X2-test for heterogeneity between recorded numbers of infants each calender month, Edwards' method, and a squared sinus function, all with or without correction for variations in general monthly birth rates. Statistical significant seasonal variations were found for anencephaly with an LMP maximum in March and for spina bifida aperta with a maximum in July. Factors which can explain such seasonality are briefly discussed.


Streptococcal infection and the chronic carrier state. Group A beta-hemolytic streptococcal pharyngitis is an extremely common problem for the family physician. Clinical signs are not reliable in making the diagnosis. Infections with few or no symptoms are common. Throat culture is the best aid to diagnosis. One-quarter or more of family contacts harbor the organism. Good mamagement includes accurate bacteriologic diagnosis, adequate use of the appropriate penicillin preparation, repeat cultures, treatment of family members, if indicated, and recognition of the chronic carrier state.


Cardiac pathology of transvenous pacemakers in dogs. Transvenous right ventricular pacemaker catheters were implanted in 18 mongrel dogs for periods of 2 to 18 months (average 4.9 months). Heart block was produced in 15 of these dogs by injection of 37 per cent formaldehyde into the interatrial septum. In the other three dogs which served as controls, no heart block was produced and no electrical stimulation was applied to the implanted catheters. After the animals had been put to death, gross and microscopic examination of the hearts revealed four categories of morphological changes: (1) connective tissue sheath formation around the catheters, (2) endocardial papillary thickening, (3) interatrial septal changes, and (4) myocardial damage. Changes 1, 2, and 4 occurred in one or more intracardiac locations in all 18 dogs. Change 3 occurred only in the 15 dogs in which heart block was produced. The most striking histologic findings were areas of cartilagenous metaplasia in endocardium an underlying myocardium and areas of marked cellular proliferation of the endocardial cells both in the endothelium and underlying stroma. Chronic implantation of transvenous intracardiac pacemaker catheters in dogs consistently produces morphologic changes which may interfere with cardiac and pacemaker function and may hinder attempts to remove nonfunctional or unneeded catheter electrodes. The changes observed appear to be related to the presence of foreign material per se and not external electrical stimulation of the heart.


Hemodynamic assessment of oral peripheral vasodilator therapy in chronic congestive heart failure: prolonged effectiveness of isosorbide dinitrate. To evaluate the effectiveness of oral vasodilator therapy in chronic congestive heart failure, 20 mg of isosorbide dinitrate or placebo was administered orally in double-blind fashion to 25 patients with congestive heart failure. In 15 patients receiving isosorbide dinitrate, pulmonary arterial wedge pressure decreased 5 minutes to 5 hours after drug administration; the peak reduction was observed at 1 hour (from 23 to 14 mm Hg; P less than 0.001). Wedge pressure decreased to normal (12 mm Hg or less) in 8 of the 15 patients (Group I) but remained greater than 12 mm Hg in 7 (Group II). Reductions in mean systemic arterial pressure, systemic vascular resistance and pressure-time per minute also occurred. Indexes of pump output were unchanged in the 15 who received isosorbide dinitrate but tended to decrease slightly in Group I. Stroke index (from 23 to 26 cc/m2) and stroke work index (from 21.4 to 24.1 g-m/m2) increased slightly but significantly (P less than 0.05) in Group II. Thus the prinicpal hemodynamic action of isorbide dinitrate is marked and sustained reduction in left ventricular filling pressure without pronounced effect on cardiac output. This agent should be used in congestive heart failure primarily for relief of congestive symptoms.


Orally administered isosorbide dinitrate in patients with and without left ventricular failure due to acute myocardial infarction. The oral effectiveness of 10 mg followed by 20 mg of isosorbide dinitrate in 21 patients with acute mycardial infarction was studied over a period of 13 hours. The patients were grouped according to initial left ventricular filling pressure: group I, pressure less than 20 mm Hg, and group II, pressure more than 20 mm Hg. Patients in group II had left ventricular failure. In both groups isosorbide dinitrate resulted in a significant decrease in pulmonary arterial pressure. The left ventricular filling pressure decreased in group I from 13.6 +/- 4.0 to 7.1 +/- 2.6 mm Hg (mean +/- 1 standard deviation) and in group II from 26.9 +/- 4.6 to 19.0 +/- 3.6 mm Hg (P less than 0.001). Cardiac output decreased in group I from 5.1 +/- 1.0 to 4.5 +/- 0.9 liters/min, whereas in group II it increased significantly from 3.5 +/- 0.8 to 4.1 to 0.9 liters/min (P less than 0.001). In both groups, peripheral arterial blood pressure decreased (P less than 0.60). Heart rate remained constant. Whether cardiac output increased or decreased was found to be dependent on the initial left ventricular filling pressure. In patients with an initially high value (above 20 mm Hg), the increase in cardiac output is probably due to the reduction of afterload. An additional factor may be the decrease in left ventricular filling pressure, which leads to an improved blood supply in the affected mural segments as a result of the decrease in the extravascular component of the coronary resistance. Significant changes in cardiac output and left ventricular filling pressure were achieved 3 to 5 hours after oral administration of isosorbide dinitrate. Clinical signs of failure were less pronounced. Isosorbide dinitrate is, therefore, a therapeutic agent in the treatment of left ventricular failure due to acute myocardial infarction.


Quality control of small-volume sterile products. A method for bacterial surveillance of small-volume sterile products in hospitals was developed and tested. The criteria for the method of quality control were to: (1) assure detection of contamination associated with touch, which could occur during the filling process; (2) be economically feasible; (3) be simple and easy to implement; and (4) be versatile in adapting to small-volume sterile packages with and without needles. Ten percent of each lot of prepackaged unit dose syringes is tested by filtration through a sterile micropore filter. The filter unit is incubated after fluid thioglycollate medium has been added. If turbidity or color change is found, further testing with blood agar and gram staining is performed to identify the organism. The effectiveness of the method was tested by adding E. coli to one lot within each of several lots tested of six products. The inoculated samples were stored under refrigeration for three days before testing. With one exception, the E. coli was detected in the samples. Growth did not occur in any of the noninoculated units. The apparent false negative result was believed to be caused by the bacteriostatic agent killing the organism during the three-day storage period.


Antimicrobial spectrum, pharmacology and therapeutic use of antibiotics. Part 1: tetracyclines. The mode of action, bacterial resistance, in vitro activity, pharmacology, dosage, adverse reactions, interactions and indications for tetracyclines are reviewed. Suggestions for the selection of a particular tetracycline are provided. It is concluded that there is only one pertinent difference among the tetracyclines, namely, that doxycycline, and probably minocycline, can be given in full dosage and with minimal risk to patients with renal impairment.


Antimicrobial spectrum, pharmacology and therapeutic use of antibiotics. Part 2: penicillins. The mechanism of action, resistance, antibacterial spectrum, clinical pharmacology, adverse effects, and therapeutic and prophylactic use of penicillins are reviewed. The choice of a penicillin is discussed. The only indication for the penicillinase-resistant penicillins is the suspected or demonstrated presence of Staphylococcus aureus. There are no important differences in therapeutic effect among oxacillin, cloxacillin, dicloxacillin or flucloxacillin by the oral route, or among oxacillin, dicloxacillin, nafcillin or methicillin parenterally. Ampicillin is especially useful for infections due to Haemophilus influenzae and Escherchia coli and for serious disease due to enterococcus and Listeria monocytogenes. Carbenicillin and ticarcillin exhibit unique activity against gram-negative bacilli (except Klebsiella).


Basal and LRH-stimulated secretion of FSH during early pregnancy. The gonadotropin response to 25 mug of LH/FSH releasing hormone (LRH) intravenously was investigated during the very first weeks of pregnancy. It was found progressively to decrease, and no response in FSH was found for more than 5 weeks. The basal levels of FSH showed the same decreasing tendency, and a few weeks after conception they were often close to the sensitivity limit of the assay. With this report we have continued our description of the changing pituitary responsiveness to LRH from conception to the puerperium. During later stages of pregnancy the plasma levels of FSH were markedly reduced, and the response was inhibited even after 500 mug of LRH intervenously. The return of the response during the puerperium showed a specific pattern with a dissociation of the response in FSH and LH. No such dissociation was found during the period of progressive inhibition during the very first weeks of pregnancy.


Fetal carbohydrate metabolism: its clinical importance. A basic understanding of fetal nutrition and metabolism is essential in the clinical management of the obstetric patient. The fetus depends upon a constant infusion of glucose for energy production and growth. Maternal glucose is the prime source of this nutrient. Alterations in maternal carbohydrate homeostasis will lead to changes in fetal metabolism. In diabetes mellitus, hyperglycemia may produce hyperinsulinemia and macrosomia. The growth-retarded fetus may have a decreased supply of maternal glucose and reduced amounts of hepatic glycogen and adipose tissue. The fetus must depend upon these stores for survival during periods of intrauterine hypoxia. In the newborn period, hypothermia and hypoxia may rapidly deplete energy reserves. With this information, the clinician may more knowledgeably manage dietary demands in the antepartum patient, fetal distress during labor, and the immediate newborn period.


Reactivity of anti-human brain serum with human lymphocytes. Specific anti-human T-cell serum was prepared in rabbits by multiple subcutaneous injections of human brain homogenates in incomplete Freund's adjuvant. The serum was exhaustively absorbed with human RBCs, lyophilized human liver, lyophilized normal human serum, and peripheral blood lymphocytes from patients with chronic lymphocytic leukemia (CLL). Specificity of the antiserum for human T lymphocytes was tested by indirect immunofluorescence. It stained 70 to 80% of lymphocytes in circulation, 95% of thymus, 27 to 35% of spleen, 5 to 10% of tonsil lymphocytes, and over 90% of phytohemagglutinin-stimulated lymphocytes in vitro. Only T-dependent areas of cryostat-sectioned human lymph nodes stained with the antiserum. It did not stain circulating lymphocytes which formed HEAC rosettes, plasma cells in marrows of multiple myeloma patients or macrophages. After removal of HEAC rosettes by centrifugation in Ficoll-Hypaque, 75% of interface cells formed E rosettes and 65 to 75% stained with the antiserum. The antiserum was used in studies of lymphocytes in chronic and acute lymphocytic leukemias, lymphomas, and other lymphoproliferative diseases. Numbers and distribution in the circulation, spleen and nodes of lymphocytes bearing the T marker were significantly altered in patients with these disorders.


Process and outcome of therapy with depressed women. The relationship between the process of psychotherapy and patient outcome, as measured by completion or relapse, was examined in an eight-month trial of therapy with outpatient depressed women. Of four therapy components analyzed, discussion of mental symptoms and overt expression of anxiety were significantly associated with relapse.


Provider expectations and consumer perceptions of the importance and value of dental care. Seventy-eight inner city mothers of third and fourth grade children in three racial groups--white, black, and American Indian--known to need dental treatment for disease on permanent teeth, were interviewed at home by a trained community resident interviewer. Sixty-two per cent of the mothers were on public assistance. Information relating to the mothers' perceptions of the importance and value of dental care both for herself and for her children were collected. Utilization data were obtained via two dental examinations conducted one year apart. Data were also collected from a sample of provider dentists via mail questionnaire. A yield of 315 usable questionnaires was obtained, a return rate of 53 per cent. Provider-dentists felt that low socioeconomic consumers do not value dental services, as compared to other types of consumer goods and services, and that they do not believe dental care is important. Low income mothers in the same city reported that they did value dental care and believed it important. Expectations of and orientations toward the importance of dental care were found discongruent between the two groups of respondents. These discongruities on the dentist-patient relationship are discussed as a barrier to utilization. Although financial resources were available to many of the study families, only 49 per cent of these children received the needed care. It is suggested that the psychological cost to a patient of seeking care in inhospitable settings may act as a barrier to utilization.


Histamine and sympathetic blockade in septic shock. The relative roles of endogenously released histamine and the sympathetic nervous system in septic shock were indirectly studied by blocking each one separately. Antihistamines in doses of 3-10 mg/kg prevented severe blood pressure drops and improved urinary output in groups treated before and after shock. Release of histamine seems to be important at least in the pathogenesis of early septic shock, although analysis of blood pressure pattern and survival implicates additional factors in late shock. Epidural block in combination with E. coli injection was detrimental, producing severe hypotension and even immediate death. Neural sympathetic tone is essential to survival in shock.


Factors involved in disruption of intestinal anastomoses. Bowel anastomoses, as performed on 181 dogs, were studied: (1) by interposing segments of colon into small bowel and vice versa, (2) by comparing clean anastomoses to those contaminated by feces before and after suturing, (3) with and without parenteral preoperative antibiotic, and (4) with and without coaptation of an inverted serosa. All animals with a timed sacrifice as well as an unexplained death had careful autopsy. Results demonstrated no difference in the healing capacity of large (91%) versus small (92%) intestine under identical circumstances. Intraluminal bacteria were of importance only if spillage caused contamination during operation and thereby subsequent infection of the peritoneal surface of the suture line. Peritonitis preceded all 28 leaks, yet the converse never occurred. Likelihood of a complicating peritonitis (67%) and thus an anastomotic leak (24%) was significantly reduced through the preoperative administration of prophylactic cefazolin (19 and 4%, respectively). A "serosal seal" also appeared important in obviating suture line disruption. Our data emphasize the value of an inverted and serosal lined anastomosis, bowel preparatory measures, prophylactic antibiotic, and the disruptive action of local bacterial peritonitis.


Chronic bullous dermatosis of childhood. The clinical features, laboratory studies, and therapeutic responses of two boys with chronic bullous dermatosis of childhood are described. Direct immunofluorescent preparations of sections from a lesion, skin adjacent to a lesion, and uninvolved skin demonstrated linear deposition of IgA at the dermoepidermal junction in all three biopsy specimens from one patient. Similar preparations from the second child were negative for staining. No circulating antibodies to skin components were detected in either child by means of multiple substrates. Neither child had clinical manifestations nor laboratory findings suggestive of an associated gastrointestinal lesion; therefore, small bowel biopsies were not performed. Immunologic studies failed to demonstrate any of the abnormalities frequently described in dermatitis herpetiformis. Both boys responded dramatically to sulfapyridine therapy.


Nevus anemicus. Donor-dominant defect.

Nevus anemicus. Donor-dominant defect. Histologic, pharmacologic, and exchange transplant studies were performed on a patient with nevus anemicus. Histologic examination disclosed no abnormalities. The only pharmacologic stimulus that produced erythema within the nevus was the alpha-blocking agent, phentolamine mesylate. Results of the transplant studies demonstrated donor dominance. This suggests that the defect in the nevus anemicus is attributable to increased sensitivity of the blood vessels to catecholamines rather than to increased alpha-adrenergic stimulation.


Clinical effect of allopurinol on preserved kidneys: a randomized double-blind study. We investigated the clinical posttransplant effect of allopurinol on preserved kidneys. Thirty-four paired kidneys from brain-dead cadavers were preserved by hypothermic pulsatile perfusion with silica gel fraction in separate cassettes. Allopurinol was added to one perfusate and omitted from the other in a randomized, double-blind, prospective plan. There was no difference in the short-term or long-term function of either group of kidneys. Allopurinol does not appear to have as consistent a beneficial effect on non-ischemically damaged human kidneys as that observed experimentally on ischemically damaged canine organs.


Toothpick perforation of the intestines. Toothpicks have been used since antiquity as instruments for mouth cleansing and as eating utensils. Toothpick injury to the gastrointestinal tract is often suspected only at the time of operation because patients rarely relate a history of swallowing toothpicks and most toothpicks are not radiopaque. The spectrum of toothpick injury to the gastrointestinal tract is illustrated by 5 patients who developed toothpick perforation of the gastrointestinal tract. Two patients died as a result of complications of toothpick injury, one of these presenting with recurrent gram negative sepsis with multiple organisms due to a duodenal-inferior vena caval toothpick fistula. In two instances the toothpicks were removed at operation and one that was penetrating the duodenum was removed with a fiberoptic duodenoscope.


Association of a circulating immunosuppressive polypeptide with operative and accidental trauma. The serum from 109 traumatized patients was examined for immunosuppressive activity which might explain diminished host immune responsiveness following operative or accidental injury. Twenty-eight fo 31 (90%) severely tralmatized patients, 25 of 60 (42%) moderately traumatized patients, and 0 of 18 minimally traumatized patients developed serum which suppressed the response of normal human lymphocytes to phytohemagglutinin. The degree and duration of serum immunosuppressive activity paralleled the severity of the clinical course but did not correlate with serum cortisol or barbiturate levels. Suppressive sera were not cytotoxic. The immunosuppressive factor(s) was contained in a low molecular weight (less than 10,000 daltons) peptide fraction and was present in 5--10 times the amount recoverable from normal serum. By size and activity the trauma serum factor resembled immunoregulatory alpha globulin, a naturally-occurring serum inhibitor of T-lymphocyte reactions. Thus, depressed immunoreactivity following trauma may be due in part to high concentrations of an endogenous immunosuppressive polypeptide.


Repair of atrial septal defect with partial anomalous pulmonary venous return from the left upper lobe. A patient with partial anomalous venous return from the left upper lobe in the presence of a large atrial septal defect is presented. The diagnosis was confirmed by selective angiographic studies. Two technical points are emphasized: first, that the exposure through a midsternal incision is excellent, and second, that the anomalous vein must be detached from its connection to the innominate or subclavian artery as high into the left chest as it is technically possible to reach. Postoperative cardiac catheterization and angiograms confirm the completeness of the repair.


Clindamycin and gentamicin for  aerobic and anaerobic sepsis. Thirty-eight adult patients with serious pleuropulmonary, soft-tissue, bone, and intra-abdominal infections caused by combinations of aerobic, facultative, and anaerobic bacteria were treated with parenterally given clindamycin phosphate and gentamicin sulfate and surgery when appropriate. Nine had associated bacteremia. In 29, infections failed to respond to other therapeutic regimens, which included penicillins, cephalosporins, aminoglycosides, and chloramphenicol. Results with clindamycin and gentamicin were excellent and were attributed primarily to the activity of clindamycin against anaerobes, particularly Bacteroides fragilis. Serum concentrations of clindamycin surpassed by manyfold the minimal inhibitory concentrations (MICs) for anaerobes. Serum concentrations of gentamicin did not consistently surpass the MICs for Enterobacteriaceae and Pseudomonas aeruginosa, although those organisms were consistently gentamicinsusceptible by disk diffusion susceptibility tests. Persistent colonization with Enterobacteriaceae, P aeruginosa, enterococci, or Candida were common, and occasionally they were significant in prolonging the clinical courses of patients with extensive infections.


Randomized study of nandrolone therapy for anemias due to bone marrow failure. A prospective, randomized, double-blind study was designed to determine the effectiveness and toxicity of nandrolone phenpropionate in the treatment of anemias due to bone marrow failure. Twenty-four patients were initially entered; 21 now may be evaluated: seven with aplastic anemia, six with myelofibrosis, and eight with refractory anemia. Six patients improved, but only three were taking nandrolone, the other three placebo. Response did not correlate with type of anemia. No serious drug toxicity was noted. One patient with myelofibrosis improved dramatically with placebo therapy alone, no longer requiring frequent transfusions because of a hemoglobin level increase from 5.4 to 15.8 gm/100 ml. We conclude that no substantial improvement of anemia due to marrow failure can be ascribed to nandrolone as given, and that clinical trials in these conditions should be controlled to exclude spontaneous remissions as a cause of apparent improvement.


Scanning electron microscopic observations on bone. The maceration technique employed in the preparation of specimens of bone for museum purposes has also been found to be of use in the preparation of fresh specimens for study with the scanning electron microscope. The technique requires less technical supervision, permits a greater underprocessing to overprocessing margin, and allows comparability of recent biopsy material with previously macerated bone specimens with no less detail than that found by other authors using other techniques on biopsy material.


Intrahepatic vascular division in the pig: basis for partial hepatectomies. Transplantation of resected hepatic fragments, with the attendant vascular and biliary tract reconstruction, presents difficulties. We have studied the intraparenchymal vascular division in the pig with a view to performing partial hepatectomies with the greastest possible anatomical support. Forty-six molds of the various vascular territories were obtained from the 31 porcine livers. Each segment of the median lobe is dependent on the adjacent lateral lobe. Its intersegmental fissure is the obligatory site for parenchymal section to be continued through horizontal portion of portal vein, hepatic artery, and left hepatic duct. A right hemihepatectomy unfailingly results in the devitalization of the left side of the liver. If the goal of a hepatectomy is the transplantation of the resected fragment, it is recommended that the right side of the liver be utilized, as its more convenient extrahepatic vascular and biliary calibre will permit pedicular conservation and anastomosis.


Temporary liver transplantation in acute liver failure. The ability of a heterotopic graft to prolong life in animals dying in hepatic coma due to liver necrosis has never been definitely established. Acute hepatic failure was produced in 15 dogs by an hour of total interruption of the hepatic blood supply. Nine dogs received an intrathoracic hepatic homograft concurrently. Nontransplanted dogs died within 21 hours in hepatic coma, while transplanted dogs survived significantly longer (P less than .001). In all transplanted dogs, biological signs of hepatic failure were corrected in 24 hours. In four animals, the graft was removed on the fifth postoperative day. Two of those survived for 10 and 15 days respectively with normal hepatic function. These results demonstrate that a temporary heterotopic liver transplant is able to support life during the acute, normally lethal phase in dogs with massive liver necrosis.


Bridge method of skin-flap delay.

Bridge method of skin-flap delay. Necrosis, a catastrophic complication of skin-falp use, is due to inadequate capillary blood flow. Delay procedures, which are based on newer information regarding skin vasculature and delay dynamics, can augment surviving-flap length. A delay procedure that used multiple skin bridges was studied in 121 flaps in 21 pigs. The result was a considerably greater amount of length augmentation than has previously been reported. This enhanced effect is related to a combination of nearly maximal sympathectomy in a highly ischemic, surgically defined experimental flap.


Surgical emergencies in the newborn.

Surgical emergencies in the newborn. Paediatric surgery is a young specialty whose rapid growth in the United Kingdom has largely been as a result of the development of neonatal surgery in the past 20 years. A decreasing birth rate, and pre-natal diagnosis of some major congenital anormalies with the possibility of termination of pregnancy, are likely to prevent further increases to neonatal surgical units. Expansion of case material is likely to come from earlier attacks on congenital heart disease, and improvement in results is more likely to come from improved respiratory management than from the development of new surgical techniques.


Comparative anaesthetic properties of various local anaesthetic agents in extradural block for labour. Various concentrations of lignocaine, etidocaine and bupivacaine in 10-ml doses of plain solutions were studied in a double-blind manner as agents for extradural analgesia to relieve the pain of labour. In 67 patients in established labour the onset time and duration of analgesia were assessed by the abolition and recurrence of the pain of uterine contractions, motor block on a 0-2 scale, dermatomal spread by pinprick testing, and arterial pressure by standard sphygmomanometry. Increasing the drug concentration reduced the onset times and increased both the duration of analgesia and the degree of motor block, but had little effect on dermatomal spread or on the frequency of hypotension. Based on the results the agents have been classified with regard to onset and duration of analgesia and degree of motor blockade.


Cell-mediated immunity in sarcoidosis: effect of corticosteroids. The paradoxical skin response in sarcoidosis is a delayed hypersensitivity skin response to an antigen such as PPD which can be elicited only when corticosteroid is present and not when it is absent. Approximately half the tuberculin-negative patients with sarcoidosis are paradoxical responders. In vitro culture of lymphocytes of 10 paradoxical responders with sarcoidosis demonstrated that a response to purified protein derivative of tuberculin (PPD) could be elicited in every patient on at least one occasion both by thymidine uptake and by macrophage migration inhibition factor (MIF) production. The response, when present, was generally at a lower level that that of normal control lymphocytes. No factor was found in the serum which could explain the low activity of the sarcoid lymphocytes in cross-over experiments with normal cells and serum. Hydrocortisone added to the in vitro lymphocyte cultures abolished lymphocyte transformation with respect to both thymidine uptake and MIF production. Varying the conditions of lymphocyte exposure to hydrocortisone, dose, duration of culture and conditions of exposure to hydrocortisone (before and after antigen) failed to enhance lymphocyte stimulation at each and every attempt. Cultures of lymphocytes obtained after oral administration of prednisone were inhibited just as if hydrocortisone had been added in vitro. However, at this time the skin responses of six out of seven patients showed delayed hypersensitivity to previously injected PPD. It is suggested that in addition to the lymphocyte defect paradoxical responders have a defect in their ability to express delayed hypersensitivity. The effect of corticosteroids is to aggravate the lymphocyte defect but in many patients the skin defect is overcome or corrected.


Isolation of ribonucleic acid polymerases I, II, and III from Saccharomyces cerevisiae. A procedure for the simultaneous purification of RNA polymerases I, II, and III from Saccharomyces cerevisiae is described. High yields of each enzyme activity are obtained, allowing the preparation of approximately 10 mg of polymerase I, 25 mg of polymerase II, and 12 mg of polymerase III from 1.2 kg of cells (wet weight). Polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate indicates RNA polymerase I contains polypeptides with molecular weights 185 000, 137 000, 41 000, 35 000, 28 000, 24 000, 20 000, 16 000, 14 500, and 12 300; RNA polymerase II contains subunits with molecular weights 170 000, 145 000, 41 000, 33 500, 28 000, 24 000, 18 000, 14 500, and 12 500; and RNA polymerase III contains polypeptides with molecular weights 160 000, 128 000, 82 000, 53 000, 41 000, 37 000, 34 000, 28 000, 24 000, 20 000, 14 500, and 10 700.


Transcription of yeast DNA by homologous RNA polymerases I and II: selective transcription of ribosomal genes by RNA polymerase I. Purified yeast DNA was transcribed by homologous RNA polymerases I and II and Escherichia coli RNA polymerase. Transcripts synthesized in vitro were analyzed by molecular hybridization with complementary DNA (cDNA) synthesized from yeast poly(A)-containing mRNA with viral reverse transcriptase and ribosomal DNA labeled in vitro by nick translation with E. coli DNA polymerase I. RNA synthesized by polymerase I and II in the presence of Mn2+ contained sequences complementary to cDNA and rDNA at a frequency consistent with random transcription of the template. Similarly, E. coli RNA polymerase synthesized an apparently random transcript in the presence of either Mn2+ or Mg2+. In contrast to these results, RNA polymerase I but not polymerase II transcripts were markedly enriched in sequences complementary to rDNA when transcription was carried out in the presence of Mg2+. The observed enrichment was 15-30-fold higher than observed for polymerase II or E. coli polymerase transcripts and is consistent with the transcript being comprised of 6-10% ribosomal sequences. These data strongly suggest that RNA polymerase I plays a critical role in selective transcription of ribosomal cistrons.


Influence of cationic triphenylmethane dyes upon DNA polymerization and product hydrolysis by Escherichia coli polymerase I. The cationic triphenylmethane dyes crystal violet, methyl green, and malachite green inhibited DNA synthesis catalyzed by Escherichia coli B polymerase I (polymerase I). Lower concentrations of the dyes inhibited DNA replication as a direct function of the proportion of AT to GC in the DNA of Clostridium perfringens, Escherichia coli, and Micrococcus lysodeikticus. When the intercalant proflavin was employed, the GC-rich micrococcal DNA was most severely inhibited. In addition, both the triphenylmethanes and proflavin inhibited product hydrolysis catalyzed by polymerase I.


Characterization of purified poly(adenylic acid)-containing messenger ribonucleic acid from Saccharomyces cerevisiae. Yeast poly(adenylic acid)-containing messenger RNA was isolated from total cellular RNA by affinity chromatography on poly(uridylic acid)-cellulose. The relative complexity of the isolated yeast mRNA was assessed by hybridization analysis with complementary DNA synthesized from the isolated messenger RNA (mRNA) with viral reverse transcriptase. Approximately 25% of the mRNA hybridized at an apparent Crt1/2 of 5 X 10(-3) mol sl.(-1), while the remainder hybridized at an average Crt1/2 of 10(-1) mol sl.-1. Poly(adenylic acid)-containing yeast mRNA was translated in vitro in a wheat germ cell-free extract, and the major polypeptides synthesized have the same molecular weight as the major proteins present in the cell. Four of these proteins were identified by coelectrophoresis and immune precipitation to be pyruvate kinase, enolase, aldolase, and glyceraldehyde-3-phosphate dehydrogenase. These data demonstrate in agreement with the hybridization results that yeast contains major mRNA species and that some of the glycolytic enzyme mRNAs make up part of the major fraction. A procedure is outlined for the preparation of yeast mRNA which is essentially free of ribosomal RNA contamination and is further enriched in the major mRNAs present in the cell.


Evidence for involvement of the electron transport system at a late step of anaerobic microbial heme synthesis. The penultimate step in heme biosynthesis, the oxidation of protoporphyrinogen to protoporphyrin, can be anaerobically coupled to the reduction of fumarate in extracts of anaerobically-grown Escherichia coli. This coupling is approximately 90% inhibied by 2-heptyl-4-hydroxy quinoline-N-oxide (HQNO), a known inhibitor of the electron transport chain. This observation suggests that the mechanism of the anaerobic oxidation of protoporphyrinogen in E. coli involves a coupling into the anaerobic electron transport system. In contrast, the aerobic oxidation of protoporphyrinogen, which occurs in mammalian and yeast mitochondria, is known to be linked directly to oxygen without the mediation of an electron transport system.


Slow fluorescence quenching of type A chloroplasts. Resolution into two components. The divalent-cation-specific ionophore A23187 is used to define two components of the slow fluorescence quenching of type a spinach chloroplasts: ionophore-reversible and ionophore-resistant quenching. Ionophore-reversible quenching predominates at relatively low light intensities and approaches saturation as light levels are increased. It is sensitive to uncouplers and to 3-(3,4-dichlorophenyl)-1,1-dimethylurea (DCMU) and is dark reversible. At high light intensities the bulk (greater than 80%) of slow fluorescence quenching is ionophore-resistant. Ionophore-resistant quenching is stimulated by carbonyl cyanide m-chlorophenyl hydrazone (CCCP) at pH 7.6 and by both CCCP and methylamine at pH 9.0. It is insensitive to DCMU and is not reversed in subsequent darkness. Taken together, the two components account for all quenching observed in Type A chloroplasts. Ionophore-reversible quenching is identified with the Mg2+-mediated fluorescence quenching described by Krause (Biochim. Biophys. Acta (1974) 333, 301-313) and by Barber and Telfer (in Membrane Transport in Plants (Dainty, J., AND Zimmermann, U., eds.), pp. 281-288, Springer-Verlag, Berlin, 1974). Ionophore-resistant quenching, a first-order process requiring high light, resembles the quenching reported by Jennings et al. (Biochim. Biophys. Acta (1976) 423, 264-274). The resolution of the fluorescence quenching phenomenon into two distinct components reconciles the apparently contradictory observations of these earlier investigations.


The effects of N-ethylmaleimide on active amino acid transport in Escherichia coli. N-Ethylmaleimide (MalNEt) binds covalently and without specificity to accessible sulfhydryl residues in proteins. In some cases specificity has been imposed on this reaction by manipulating reaction conditions, yielding information concerning both enzyme mechanism and the identity of specific proteins (for example C.F. Fox and E.P. Kennedy (1965) Proc. Natl. Acad. Sci. u.s. 54, 891-899) and R.E. McCarty and J. Fagan (1973) Biochemistry 12, 1503-1507). We have examined the effects of MalNEt on the active accumulation of nine amino acids by Escherichia coli strains ML 308-225 and DL 54. Whole cells have been used in order that transport systems both dependent on and independent of periplasmic binding proteins could be studied under various conditions of energy supply for transport. Our results suggest that the systems transporting ornithine, phenylalanine and proline are those most likely to undergo inactivation by direct reaction of MalNEt with the transport apparatus, rather than merely via side effects such as interruption of their energy supply. The inhibition of proline transport is specifically enhanced by the presence of proline, competitive inhibitors of proline transport, or carbonylcyanide p-trifluoromethyoxyphenylhydrazone during MalNEt treatment. The other eight systems tested showed no analogous effects.


Induction of lesions in deoxyribonucleic acid by low molecular weight substances from normal and colicin E2-treated cells of Escherichia coli. A fraction containing a variety of low molecular weight substances was extracted into 80% aqueous acetone from both a colicin E2-treated cell culture of Escherichia coli and an untreated one. The extract was divided into five fractions by Sephadex G15 chromatography. One of them, Fraction B, was separated into three subfractions by Sephadex G10 chromatography. Two subfractions, Fraction BI and Fraction BII, were further fractionated by several chromatographic systems. DNA was incubated with an aliquot from each of these fractions and was then analyzed by sedimentation in an alkaline sucrose density gradient. The activity which caused a decrease in the sedimentation coefficient of the DNA was found in some of these fractions. The activity from colicin E2-treated cells was compared with that from untreated ones. It was revealed that colicin E2 induces some increases in the activity toward DNA in one of the subfractions, Fraction BI, and also causes the appearance of a new species in another fraction, Fraction BII, which potentiates the activity in Fraction BI. These colicin E2-induced changes appeared at 5 min after the addition of colicin E2. The possible significance of such reactions for the action of colicin E2 are discussed.


The restriction endonuclease cleavage map of rat liver mitochondrial DNA. Mitochondrial DNA from rat liver contains six sites for cleavage by the restriction endonucleases Hind III and EcoRI. A large stretch of DNA, comprising about 40% of the mitochondrial genome is not cleaved by either of the enzymes; eight cleavage sites are located on a DNA stretch of 35% of the genome length suggestive of an unequal distribution of the A - T baspairs over the molecule. The number of Hind III and Eco R I fragments is much higher than reported for other mammalian mitochondrial DNAs up to now.


Synthesis of guanosine 5'-diphosphate, 3'-diphosphate in spot mutants of Escherichia coli. The synthesis of ppGpp in spoT- mutants of Escherichia coli has been invesitgated. In these mutants the first-order rate constant for ppGpp breakdown is low, and pppGpp is barely detectable. It is shown that the rate of pppGpp, and hence ppGpp, synthesis is strongly reduced compared with that observed in spot+ strains. The low rate of magic spot synthesis satisfactorily explains the low levels of pppGpp in spoT- mutants. The pentaphosphate very probably is the precursor of ppGpp as it is in wild-type, i.e. spoT+, strains.


The specificity of the chemical modification of N6-delta 2-(isopentenyl)adenosine in purified yeast tRNA Ser. The specific modification of N6-delta 2-(isopentenyl)adenosine in purified tRNA Ser yeast by mild treatment with KMnO4 and I2 was studied. N6-delta 2-(isopentenyl)adenosine in tRNA SER is specifically modified by iodination, providing us with a suitable method for the quantitative determination of N6-delta 2-(isopentenyl)adenosine in tRNA was found to contain 114 +/- 8 pmol/A260nm unit of N6-delta 2-(isopentenyl)adenosine and gave three labelled fractions on an RPC-5 column. The product obtained after KMnO4 treatment of tRNA Ser was not homogeneous. The enzymatic "reisopentenylation" of KMnO4-treated tRNA Ser resulted in the regeneration of only traces of the original molecule(s). Most of them had been damaged either by the KMnO4 treatment or in the incubation mixture used for "reisopentenylation".


Aminoacylation of rat liver transfer RNA with L-penicillamine. On the specificity of the aminoacylation reaction. L-]14C]Penicillamine is bound to RNA from rat liver in an in vitro reaction catalyzed by rat liver aminoacyl-tRNA synthetases. Addition of certain naturally occuring amino acids results in a significant decrease of L-penicillamine binding. The most potent inhibitor of this binding is L-valine, followed by L-isoleucine and L-threonine. Amino acids without structural relationship to L-penicillamine in the non-functional part of the molecule, such as L-phenylalanine, are ineffective. Studies on the competition of L-penicillamine and L-isoleucine, respectively, with L-valine demonstrate the high specificity of the aminoacylation reaction. They show that the change of L-penicillamine binding to tRNA Val is considerably lower than that of L-valine.


Toyocamycin inhibition of ribosomal ribonucleic acid processing in an osmotic-sensitive adenosine-utilizing Saccharomyces cerevisiae mutant. An adenosine-utilizing mutant of Saccharomyces cerevisiae (SY 15 ado) is isolated after remutagenesis of an osmotic-sensitive strain, auxotrophic for adenine, with ethyl methanesulfonate. It is shown that the SY15ado mutant can be used to achieve experimental conditions under which cell growth and RNA Synthesis are directly dependent on exogenous adenosine. After starvation for adenosine, toyocamycin is incorporated into pre-rRNA chains of SY15ado cells replacing adenosine residues. The extent of this replacement depends on the concentration of added toyocamycin. Lower doses slow down processing of pre-rRNA into mature rRNA with an accumulation of 27 S and 20 S pre-rRNA. At higher concentrations toyocamycin blocks the last steps of pre-rRNA processing i.e. the conversions 27 S pre-rRNA  leads to 25 S rRNA and 20 S pre-rRNA leads to 18 S rRNA. It appears that the main site of toyocamycin action is at the last steps of ribosome formation, while transcription and the early stages of pre-RNA processing are less affected.


The mechanism of inhibition of bacteriophage T7 RNA synthesis by acridines, diacridines and actinomycin D. A homologous series of diacridines, as well as 9-amino acridine, were assayed for their ability to interfere with the synthesis of RNA (bands U-VI) by bacteriophage T7 DNA-dependent RNA polymerase transcribing T7 DNA in vitro; their action was compared to that of actinomycin D. It was found that, in contrast to actinomycin D which inhibits chain elongation, the acridines tested inhibited chain initiation only; no evidence for inhibition of chain elongation was noted. No clear-cut differentiation between single and double intercalators on the mechanism of inhibition of RNA synthesis could be determined, except that the latter are more potent inhibitors. However, it appears that diacridines connected with a diethyldiamine and a butyldiamine chain are less inhibitory to the synthesis of the RNA of Bands III and IV. The results furthermore indicate that the estimation of the number average molecular weight alone, without identification of the product RNA, is a potentially misleading method of determining the mode of action of these drugs.


Triton X-100 activates nucleoside triphosphate-dependent, recBC-dependent DNA synthesis in toluene-treated Escherichia coli. Escherichia coli cells whose chromosome replication has been terminated in vivo, either by growth into stationary phase or by incubation of a mutant carrying a temperature-sensitive initiation mutation under restrictive conditions, are inactive in in vitro DNA synthesis as measured in toluene-treated cells. Addition of the non-ionic detergent Triton X-100 to such inactive systems results in a marked stimulation of ATP-dependent in vitro DNA synthesis. This Triton-stimulated DNA synthesis appears to proceed by a semi-conservative mechanism, in that DNA synthesized in vitro in the presence of a density labeled precursor bands in CsCl equilibrium centrifugation at a hybrid density. Neutral sucrose gradient centrifugation demonstrates that most of this hybrid material exhibits a molecular weight in excess of 1 X 10(7). Triton-stimulated synthesis requires the presence of DNA polymerase III, as does normal in vivo replication. We show here, however, several anomalous properties of the DNA synthesis in the Triton/toluene system. In particular, Triton-stimulated synthesis is absent in cells harboring a recB mutation which lack the ATP-dependent exonuclease V, an enzyme implicated in recombinational repair synthesis in vivo. Furthermore, the ATP requirement for Triton-stimulated synthesis is relatively non-sepcific, and a variety of nucleoside triphosphates can effectively substitute for ATP. Finally, despite their high molecular weight in neutral sucrose gradient centrifugation, Triton-stimulated DNA synthesis generates DNA molecules of low molecular weight (less than 500 000) as determined by alkaline sucrose gradient centrifugation. In contrast, DNA synthesis in the normal toluene-treated cell system is not dependent on recB activity, shows a nearly absolute requirement for ATP which cannot be replaced by other nucleoside triphosphates, and produces molecules of far greater molecular weight as measured on alkaline sucrose gradients. Taken altogether the data strongly suggest that Triton activates an unusual form of DNA synthesis in toluene-treated cells which shows both repair and replicative aspects. These results caution against the use of Triton-activated toluene-treated cells system, for studying simple replicative DNA synthesis.


The 30 S subunit of the Escherichia coli ribosome. Topographical model of its component proteins. This topographical model of the proteins of the 30 S subunit of the Escherichia coli ribosome was built to be consistent with the 37 published spectroscopic and chemical experiments that indicate proximity and with the two neutron diffraction experiments that indicate S3 and S7 as well as S2 and S5 to be separated by 110 A. The model is quite consistent with the protein arrangement suggested by assembly pathways, the various RNA binding sites, and the streptomycin-associated proteins, This consistency is encouraging since none of these data were considered during the construction of the model. The model differs significantly from those proposed by Traut et at. ((1974) Ribosomes 271-308) and by Tischendorf et al. ((1975) Proc. Natl. Acad. Sei. U.S. 72, 4820-4824).


Spectral studies of the interactions of Escherichia coli alkaline phosphatase with 4-(4-aminophenylazo)-phenylarsonic acid. Escherichia coli alkaline phosphatase (EC 3.1.3.1) is reversibly inhibited by a variety of phenylarsonic acids, including some N-haloacetylated derivatives. The inhibition is of the competitive type, and Ki values are reported. The action on the enzyme of one of the arsonate inhibitors, the azo dye, 4-(4-aminophenylazo)-phenylarsonic acid was studied in detail, using spectrophotometric and kinetic methods. The azo dye binds more strongly to E. coli alkaline phosphatase than do the other arsonates. Spectrophotometric titration indicates the presence of a single, strong dye-binding site on the enzyme dimer molecule in the concentration range covered. In 0.1 M Tris - HCl buffer pH 8.0, 25 degrees C K diss for the dye - enzyme complex is 1.50 - 10(-5) M as determined by spectrophotometric titration. This value is in good agreement with the Ki = 1.30 - 10(-5) M obtained from kinetic measurements. The dye can be displaced from alkaline phosphatase by phosphate and competitive inhibitor 2-aminoethyl phosphonate. These results indicate that the dye binds with its arsonic acid group to the anion binding site of the active site of the enzyme. The binding of the dye to the native enzyme is associated with a red shift in the visible spectrum of the dye. It seems that the aromatic portion of the dye interacts with a hydrophobic region close to the anion binding site. The spectrum of the dye is not changed in the presence of the apoenzyme. When zinc is added to an apoenzyme-dye solution, the spectral changes of the dye depend on both the ratio of zinc per apoenzyme and the pH. The presence of Mg2+ had no effect on the observed phenomenon.


Effect of propranolol on platelet function. Excessive reactivity of blood platelets may contribute to atherosclerotic vascular disease. Hence drugs which alter platelet function may be protective. Prompted by findings that propranolol therapy normalized hyperactive platelet aggregation in patients with coronary artery disease, we studied propranolol in vitro to assess its action on platelets. At concentrations similar to those achieved in vivo (0.1-1 muM), propranolol raised the thresholds for aggregation of some normal paltelets by adenosine diphosphate (ADP). At higher concentrations (10-50 muM), propranolol abolished the second wave of platelet aggregation induced by ADP and epinephrine, and inhibited aggregation induced by collagen, thrombin, and the ionophore A23187. Propanolol blocked the release of 14C-serotonin from platelets, inhibited platelet adhesion to collagen, and interfered with clot retraction. Propranolol blocked ionophore-induced uptake of 45Ca by platelets. Inhibition appeared unrelated to beta-adrenergic blockage, as d(+) propranolol (which lacks beta-blocking activity) was equipotent with 1(-) propranolol. Moreover, practolol, a beta-blockading drug which is nonlipophilic, did not inhibit platelet function. These studies suggested that propranolol, like local anesthetics, decreased platelet responsiveness by a direct action on the platelet membrane, possibly by interfering with calcium availability. Modulation of platelet function by propranolol may occur at concentrations achieved at usual clinical doses of the drug.


Hematopoietic stem cells: effect of preirradiation, bleeding, and erythropoietin on thrombopoietic differentiation. A method of measuring differentiation of stem cells towards platelets is described using syngeneic bone marrow injected into lethally irradiated mice. Fourteen days after such injection, the platelet counts are found to be proportional to the number of bone marrow cells injected and can be used as a measure of platelet progenitors. Perturbation of the milieu in which the transplanted marrow is placed by host preirradiation, bleeding, or erythropoietin administration leads to enhanced thrombopoiesis. It has been shown previously that similar perturbation favors erythropoiesis at the expense of granulopoiesis. The data from these and other experiments appear to be consistent, with a model of the stem cell compartment as a continuum with proliferative activity increasing as commitment is restricted. These functions vary inversely with the capacity for self-renewal. The various stem cell assays measure different ranges of stem cells, but overlap within this continuum.


IgE myeloma with osteoblastic lesions.

IgE myeloma with osteoblastic lesions. A 69-yr-old man with persistent anemia had multiple myeloma with an IgE-type kappa M component and Bence Jones proteinuria. Bone x-rays revealed occasional lytic lesions associated with a diffuse sclerotic reaction throughout the skeleton. Special bone histologic studies utilizing tetracycline labeling, undercalcified sections, and microradiography confirmed active osteoblastic activity. This case was compared with the four previously reported cases of IgE myeloma, one of which also had osteosclerosis.


Prognosis in acquired aplastic anemia. An approach in the selection of patients for allogeneic bone marrow transplantation. In a retrospective study, factors influencing the eventual course and outcome of patients suffering from aplastic anaemia were analysed. Of the 62 patients with pancytopenia concomitant with an aplastic or hypoplastic bone marrow, 36 have died during the first 24 months following diagnosis, 27 of these 36 cases within the first six months. 26 patients survived more than two years after presentation, but a further six of these cases succumbed during the following months. Of the 62 cases, 46 had neutrophil counts under 1 X 10(9)/l and platelet counts under 20 X 10(9)/l. These cases were subdivided according to their reticulocyte levels. In the age group of patients between 10 and 35 years, all those patients having more than 10,000/mul reticulocytes survived more than two years with only one exception, whereas only one of the 11 patients having reticulocyte counts below 10,000/mul has survived. In our series, the initial neutrophil and platelet counts were not of predictive value in identifying poor prognosis patients. The initial reticulocyte counts, however, appear to be a valid parameter for selecting patients in two groups, one with a favorable, and the other with an extremely unfavorable prognosis on conservative treatment. Young individuals with a poor predicted prognosis could thus be defined as possible candidates for bone marrow transplantation.


The clouded crystal ball and the library profession. Growing awareness of the transition from an industrial age to a communication- and knowledge-based economy appears reflected in some changing directions in libraries. Major trends include (1) a change in management practices, (2) a realignment of operational goals away from technical processing activities to client-oriented outreach services, and (3) the identification of educational functions as a primary professional role. The twin concepts of knowledge utilization and information brokering are beginning to have an impact on the definition of the librarian's role.


Dimer X in hysterosalpingography.

Dimer X in hysterosalpingography. The incidence of abdominal pain during hysterosalpingography was assessed from replies to postal questionnaires completed by 42 patients receiving Diaginol Viscous and 23 patients receiving Dimer X: the questionnaires were analysed using a double-blind technique. In the Diaginol Viscous group, 58.5% of patients experienced moderate or severe pain during the injection as compared with an incidence of only 19% in the group receiving Dimer X. In three of tha patients receiving Diaginol Viscous, there was brief loss of consciousness. Radiographic quality was satisfactory with both contrast media. After effects of hysterosalpingography were relatively common and included: lower abdominal pain; vaginal bleeding; temporary difficulty in walking; menstrual disturbances in subsequent periods. No correlation could be demonstrated between the type of medium used and the incidence of these after effects.


Coagulation changes in sensitized canine renal allografts. Coagulation changes within kidney homotransplants to sensitized canine recipients have been studied by assessing the arteriovenous gradients of formed blood elements and coagulation factors across the organ. It is confirmed that hyperacute rejection is accompanied by evidence of intravascular coagulation within the graft, which is maximal during the first 20 minutes after revascularization. Attempts were made to prolong the survival of the grafts by the use of cytotosine arabinoside, methylprednisolone, heparin and azathioprine. In some instances, the severity of the intravascular coagulation was reduced but it did not prove possible to extend the survival of the kidneys beyond 24 hours.


Increased sensitivity to nitrazepam in old age. The effects of a single 10 mg oral dose of nitrazepam were compared with those of a placebo in healthy young and old people. Both the young and the elderly slept better on three successive nights after nitrazepam but they felt less awake at 12 and 36 hours (P less than 0-01). Elderly people made significantly more mistakes in a psychomotor test than did the young, despite similar plasma concentrations of nitrazepam and half lives in the two groups. This difference in response to psychomotor testing is probably explained by an increased sensitivity of the ageing brain to the action of nitrazepam.


Acupuncture analgesia: an experimental investigation. A study was designed to establish whether acupuncture has any analgesic properties beyond those of suggestion. In three one-hour experimental sessions the increases in detection thresholds and tolerances for thermal pain at six body locations on 12 subjects were compared. A control session (without needles) was followed by one session in which electrically stimulated needles were inserted in accord with Chinese practice, and another in which the needles were inserted to avoid all recognised acupuncture "points." Acupuncture was significantly more effective than suggestion in raising overall body pain thresholds but just below significance for tolerances. A significant disproportionate effect on the epigastrium, predicted by the choice of acupuncture points, was found for tolerances but not thresholds.


Dreaming, fenfluramine, and vitamin C.

Dreaming, fenfluramine, and vitamin C. The effect of increasing doses of fenfluramine on dream patterns was studied in 20 patients receiving a reducing diet with or without a controlled dietary intake of vitamin C daily. The dream pattern was unchanged in six patients and dreams disappeared in another who normally dreamed often. In 13 patients dreams increased in frequency and intensity, and in five the dreams assumed frightening proportions. There was a significant straight-line relation between response and the size of the dose. When placebo tablets were given to four patients their dreams disappeared or assumed their pretreatment normal pattern. Absence of vitamin C from the diet did not significantly affect the dream pattern. That fenfluramine has dose-related cerebral effects should be remembered in patients with a history of mental illness.


Identification of catecholamine and luteinizing hormone-releasing hormone (LHRH)-containing neurons in primary cultures of dispersed cells of the basal hypothalamus. Primary cultures of dispersed cells were prepared from 3-5 mg pieces of basal hypothalami of 10-12-day-old rats. The tissue included median eminence, arcuate nucleus and variable amounts of adjacent hypothalamus and preoptic area. The dispersion procedure consisted basically of tissue trypsinization and mechanical dissociation of cells. They were cultured in a modified L-15 medium in an air atmosphere. Neurons survived approximately 3 months. On the basis of morphological characteristics, two basic cell types could be distinguished. One was a larger (50 mum diameter) multipolar cell; microspectrofluorometric analysis revealed that a small percentage of these neurons contained a catecholamine. A second type was smaller, fusiform or ovoid and generally bipolar; a significant number of these were immunoreactive for the releasing hormone LHRH.


Acute epiglottitis in children: management of 27 consecutive cases with nasotracheal intubation, with special emphasis on anaesthetic considerations. Twenty-seven consecutive cases of acute epiglottitis in children were treated by nasotracheal intubation during a 25-month period. The duration of intubation averaged 44.2 hours. No mortality or morbidity occurred. Mean hospitalization was 4.5 days. Anaesthetic techniques are discussed. Ketamine is a somewhat controversial choice for these patients as it can enhance excitement, restlessness, and accidental extubation. This study reconfirms the ease of maintaining an assured airway by nasotracheal intubation in cases of acute epiglottitis.


Clinical trial of etomidate. Preliminary observations on a new non-barbiturate induction agent. This is a preliminary report of our clinical experience with etomidate, a new intravenous non-barbiturate anaesthetic agent. Thirty-two patients undergoing minor surgical procedures were anaesthetized, induction being with etomidate 0.3 mg/kg body weight. Induction was fast and smooth. Twenty-eight per cent of the patients complained of pain at site of injection but the pain disappeared on flushing with water for injection. Following etomidate injection, 37.5 per cent of patients developed myoclonic movements which were usually mild and self-limiting. We were impressed by the relative stability of the cardiovascular and respiratory systems. Etomidate looks promising and further work is in progress on other aspects of this drug.


Chinese acupuncture.

Chinese acupuncture. Acupuncture has been described as it is practiced in the People's Republic of China. To understand fully the preoccupation of the Chinese with this mode of treatment one must be familiar with its economic, historical and cultural background. Since conditions in Western countries are totally different from those in China it is obvious that acupuncture cannot be transplanted in toto from country to country, but that it requires reassessment of its usefulness as a treatment modality. Although further basic and clinical studies must be carried out, it would appear at the moment that acupuncture may have a useful place as yet and additional means of treating pain, especially in areas in which present treatment is less than satisfactory. At the moment no clear indication is obvious for acupuncture anaesthesia in countries in which this specialty is well developed and where adequate numbers of trained anaesthetists are available.


Comparison of analgesia by intravenous butorphanol and meperidine in patients with post-operative pain. Intravenous doses of butorphanol tartrate (0.5 mg, 1.0 mg and 2.0 mg) and meperidine hydrochloride (20 mg and 40 mg) were compared under controlled conditions employing a double blind study design. Informed consent was obtained from all post-operative patients suffering from moderate to severe pain who participated in this study. Approximately 25 patients were included in each group. The data from 125 patients were subjected to statistical analysis. The results indicated that butorphanol is approximately 40 to 50 times more potent than meperidine. In addition, at most of the time intervals, there were no statistically significant differences between the responses to butorphanol 0.5 mg and 1 mg and meperidine 20 mg and 40 mg; but the response to butorphanol 2 mg was significantly (p less than 0.05) better than the low dose of each agent. The low doses of butorphanol (0.5 mg) and meperidine (20 mg) appear to have an effective duration of action of less than two hours. The larger doses (butorphanol 1.0 mg and 2.0 mg and meperidine 40 mg) appeared to produce a two- to four-hour duration of action. The largest butorphanol dose (2.0 mg) appeared to produce the longest duration of action. A comparison of the test groups with respect to the incidence and type of side effects showed that butorphanol 2.0 mg produced a greater incidence of drowsiness (39 per cent). The overall incidence of drowsiness for patients receiving either the 0.5 mg or 1.0 mg dose of butorphanol was 12 per cent, as compared with an 8 per cent overall incidence in the meperidine group. The incidence of other side effects was relatively low in all test groups. No significant differences were noted among the groups with regard to the onset (usually less than or equal to 30 minutes post-therapy) or the duration (usually less than or equal to 2 hours) of side effects. Butorphanol appears to be a safe and effective analgesic for the relief of moderate to severe post-operative pain.


Antimicrobial susceptibility of Salmonella isolates from the broiler chicken industry in Ontario. Antibacterial drug resistance among 219 salmonella isolates recovered during 1974 from poultry and poultry environments at the various production stages of broiler chickens in three integrated Ontario companies are recorded. All isolates were susceptible to ampicillin, trimethroprim-sulfamethoxazole complex, furazolidone, cephaloridine and amoxicillin. A relative increase in resistance to tetracycline and streptomycin with an accompanying decrease in resistance to triple sulfa compound was recorded when compared to a previous investigation of avian salmonella isolates in Ontario. The percentage and patterns of antimicrobial resistance were comparable at the various stages of production. Resistance to tetracycline and streptomycin was the most common pattern found among both Salmonella typhimurium and other serotypes. A notably high prevalence of resistance was found among Salmonella enteritidis isolates including some isolates with R factors for chloramphenicol resistance. This latter finding is of particular concern because of the high prevalence of this serotype in poultry and in human salmonellosis.