Atrio-ventricular canal malformations. Recent surgical techniques.

Twenty patients with atrio-ventricular canal malformations (5 complete and 15 partial forms) were operated upon during the last two years, using new surgical techniques. The repair of the complete form based on a three-leaflet three-commissure mitral valve concept, was accomplished by: a) Two separate partitioning patches (one ventricular, one atrial), b) mitral and tricuspid valve attachment in between, c) no cleft sutures, d) correction of subvalvular apparatus abnormalities, e) commissuroplasty. The repair of the partial form was obtained by: a) Valvular and subvalvular repair of the lesions when present, b) patch closure of the ostium primum defect suturing on the tricuspid side. All patients survived operation and exhibited normal sinus rhythm. Residual mitral incompetence proved to be less frequent as compared to previous techniques.


Transposition of the great arteries. Successful Senning's operation in 35 consecutive patients.

Mustard's operation for TGA (transposition of the great arteries) has been obstructive complications. In order to try to avoid these complications, we used Senning's operation for TGA. Our experience in 35 consecutive cases is reported. There were no operative or late deaths. Four patients had a PDA; three had a significant VSD with subpulmonary stenosis in two. Previous atrial septectomy and persistent LSVC did not represent contraindications to this procedure. The postoperative course has been smooth and uneventful in all patients. Follow-up periods of one to twenty months demonstrated sinus rhythm in all patients and there were no significant gradients between the venae cavae and the new systemic atrium in 12 reinvestigated patients. On the basis of these results, Senning's operation is recommended as a valid alternative to Mustard's operation.


Surgical treatment of tracheal stenosis.

During the last 3 1/2 years 8 patients underwent segmental resection of the trachea and one patient underwent resection of the carina at the Department of Surgery, University Hospital, Köln. Follow-up investigation in 6 month intervals showed good results in 6 patients. The complicated course of 1 of our patients with tumor infiltration of the trachea is discussed. In this case a large esophagotracheal fistula was covered with a vascularized esophageal segment. Suggestions for surgical indications in segmental resection of benign esophageal stenosis are outlined.


Uptake and metabolism of female sex steroids by isolated small neurons and other cell fractions from the rat medial basal hypothalamus.

Rat medial basal hypothalami (MBH) and sections of cerebral cortex (CC) were dissociated with trypsin to prepare single cells and subcellular fractions. They were then separated into four fractions on a discontinuous sucrose gradient. The small neurons in Fraction D were highly purified. Fraction A had synaptosomes, myelin and other cell particulates. Fraction B had glial cells, neurons and a few synaptosomes. Fraction C had large neurons and red blood cells. All four fractions contained LHRH, but most (62.5%) of this hormone was present in Fraction A. Dissociated cell suspensions were incubated with [3H]-steroids, with and without a 100-fold excess of unlabeled steroids, then separated on sucrose gradients. In most fractions the total uptake and specific uptake of [3H]-progesterone, [3H]-5 alpha-pregnane-3,20-dione (5 alpha-dihydroprogesterone) and [3H]-17 beta-estradiol were greater for the dissociated cells from the MBH than the CC. The dissociated cells and cell particulates in all four fractions from the MBH and CC metabolized progesterone, 5 alpha-dihydroprogesterone and 17 beta-estradiol. These results indicate that hypothalamic neurons contain small amounts of LHRH and retain the ability to take up and metabolize progesterone, 5 alpha-dihydroprogesterone and 17 beta-estradiol.


[Late recurrence of ameloblastoma].

Two cases of late recurrence (31 and 33 years after radical surgery) of an ameloblastoma induced us to explain our operative approach on the basis of experience with 37 patients operated on for ameloblastoma at our clinic. With special consideration of the biology, clinic and histopathology of this tumour, we have tried to establish operative guidelines with regard to radical surgery. We arrived at the conclusion that ameloblastomas regarded as malignant should be treated by radical surgery; and those considered to be benign, by conservative surgery, individual decisions being imperative. Our clinical observations and analyses are compared with the results of other authors.


[Use of the intra-alveolar GR (gelatin-resorcinol) dressing after tooth extraction in patients with hemorrhagic diathesis].

The suitability of an intra-alveolar gelatin-resorcinol dressing for controlling bleeding was tested in 118 tooth extractions on a total of 87 patients. Plain advantages of the dressing are: prompt haemostasis (which in most cases avoids hospitalization and substitution therapy), low cost, and easy application. The dressing is not always reliable in controlling bleeding after milk tooth extraction.


[Microwave therapy in outpatient oral surgery].

The biological action of microwave therapy is due to the conversion of high-frequency electromagnetic waves to heat that is produced directly in the tissue at the radiation area. It is a deep heating procedure of limited range with low-level exposure to the subcutaneous fatty tissue; it may be used in subacute and chronic infectious inflammatory conditions, after surgical interventions, in affections of the salivary glands and of the maxillary sinuses, and also in temporo-mandibular joint disorders and facial neuralgias. As a rule, irradiation by microwaves is only a supporting treatment. Its advantages are above all: easy application; great economy; versatility; uniform, locally limited distribution of heat with low-level exposure to the fatty tissue; virtual safety.


[Antibacterial effect of Ankerplast Spray].

The diffusion test yielded no satisfactory results. In the tube test, both the spray and the solvent (in a dilution of 1:4 and 1:8, respectively) proved to be bacteriostatically active against enterococci, Staphylococcus aureus, Escheria coli, Proteus, and Pseudomonas aeruginosa. These germs were killed within 30 minutes in the test for bactericidal activity, whereas the reference substance (1% phenol) required 1--2 hours, except against the last-named germ. Even the copolymer exerted a bactericidal effect, it is true, but only within 8 or 24 hours. The following results were obtained from the spray test with agar plate cultures: Streptococcus viridans species, streptococci, Diplococcus pneumoniae, Escheria coli, and Proteus were killed, whereas others survived under the plastic film for up to 9 days. Klebsiella and Pseudomonas aeruginosa had grown through the film within 7 days. In vivo experiments demonstrated a very potent antibacterial activity on the skin under the spray film.


Development of donor-specific B lymphocyte antibodies after renal transplantation. No correlation with graft outcome.

Serum samples from 66 recipients of first cadaver donor renal transplants were screened for cytotoxic antibodies to normal T and B lymphocytes and B lymphocytes from chronic lymphocytic leukaemia patients. In addition, the sera of 44 patients were tested with the B lymphocytes of their respective donors. Donor-specific antibodies were found in 10 of 16 (63%) recipients who had lost their transplant within 2 months, and in 17 of 28 (61%) patients with functioning transplants at 2 months. No correlation was found between the development of B lymphocyte antibodies (either against the panel or the donor) and the onset of an acute rejection episode. In the 17 patients with a successful transplant and donor-specific antibodies, six (35%) had not experienced a rejection episode and another seven patients developed their antibodies after the appearance of the first rejection episode. Thus, our results show that the appearance of donor-specific B lymphocyte antibodies after transplantation is not indicative of graft failure or predictive of acute rejection episodes. However, the common occurrence of such antibodies raises questions concerning the nature of the antigenic stimulus, the specificity of the antibodies, and their role (if any) in transplantation.


A quantitative comparison of whole antibody and F(ab')2 in kidney allograft enhancement.

Whole antiserum, IgG, and a greater than 99% pure F(ab')2 preparation were compared for their ability to enhance Lewis renal allografts in DA recipients. Despite having unimpaired antigen-binding capacity, the DA anti-Lewis F(ab')2 was virtually ineffective at the highest dose tested, and was calculated to be a minimum of 100 times less effective than whole antibody. The administration of a 10-fold excess of F(ab')2 before an effective dose of IgG did not block the enhancing effect of the latter.


Beneficial effect of blood transfusion. Role of the time interval between the last transfusion and transplantation.

We analyzed the effect of blood transfusion (BT) on kidney allograft survival in 163 recipients. Transfused recipients (121) had better graft outcome than those never transfused (42), the difference being statistically significant at 3, 6, 12, and 24 months; however, the transfused group had a longer period of hemodialysis (P = 0.01). HLA antigen distribution does not bias the data. The group who had received the last BT within 3 months before grafting had a significantly better graft outcome than the nontransfused group (P less than 0.05 at 3, 6, and 24 months). They also did better (but not significantly) than the group who had been transfused more than 6 months before grafting. The group receiving two to five BTs had the highest rate of graft survival (P less than 0.05, 0.001, and 0.05 at 6, 12, and 24 months) as compared to the nontransfused. Practical suggestions for systematic BTs during hemodialysis are made.


Technique of organ removal and fate of kidney grafts from liver donors.

The fate of 42 kidney grafts taken from heart-beating, ventilated donors at the same time as removal of the liver for allografting is reported, and is compared with 50 kidney grafts taken from heart-beating, ventilated donors whose ventilators were electively switched off either during or immediately before kidney removal. The fate of 32 kidney grafts taken from donors classified as "dead on arrival" at the admitting hospital is also reported. Onset of life-supporting graft function was significantly earlier among kidneys from the "liver donor" group. Consequently, immediate postoperative dialysis requirements were significantly less in recipients of this group of kidneys. Early graft survival, the incidence of graft primary nonfunction, failure of first and second kidney grafts, and recipient survival were not significantly different when comparing liver donor and "ventilator switch off" kidneys. No constant relationship was apparent in any donor group between graft fate and the anoxic and ischaemic times the graft was exposed to during organ removal and reimplantation.


Orthotopic liver transplantation in the rat. Technique using cuff for portal vein anastomosis and biliary drainage.

In orthotopic liver transplantation in the rat, cuff techniques have been developed for anastomoses of the portal vein and bile duct. These techniques have shortened the clamping time of the portal vein and have resulted in fewer biliary complications improving survival of the liver graft. Eighty-three per cent of the grafted animals have survived for 1 week and several animals have survived for more than 6 months. We believe that use of the cuff method technically simplifies microvascular anastomoses. It may be particularly useful for anastomosis of the portal vein after machine preservation of the donor rat liver.


The behavior of H-Y-incompatible neonatal skin grafts in rats.

It has been well documented that virgin female rats previously systemically sensitized against H-Y antigen almost invariably reject male skin isografts of adult origin. However, when the donor is a neonatal animal, these H-Y-incompatible grafts are often permanently accepted. Furthermore, such neonatal male skin grafts are frequently able to induce a state of unresponsiveness to subsequent grafts of adult male skin. This ability to induce tolerance is evidently dependent upon the persistence of the neonatal skin graft as it does not occur if the neonatal graft is rejected. Thus, the behavior of H-Y-incompatible neonatal skin grafts in rats parallels their behavior in mice.


Past, present, and future aspects of histocompatibility.

We have stressed problems attendant on studies of the MHC, ignoring non-HLA factors and their role in allograft immunity. Many other topics could have been chosen for discussion is any such overview; our selection reflects our own interests. We felt assured, however, that excellent coverage by our many colleagues of the diverse and varied aspects of histocompatibility not approached in this summary has allowed us this freedom.


Pretransplant dialysis and blood transfusion--correlation with cadaveric kidney graft survival.

Renal graft survival was better for the patients receiving blood transfusions or treated with dialysis before transplantation. Graft survival was more strongly correlated with pretransplant dialysis than with blood transfusion.


Effect of blood transfusions on renal allograft survival.

One and two-year allograft survival rates of 117 first and 20 second consecutive cadaveric renal allografts are analyzed. The following observations were made: (1) Pretransplant blood transfusions may not improve rate of allograft survival per se. (2) Pretransplant blood transfusions may, however, reduce the number and the severity of rejection episodes in the early posttransplantation period. Thus, the allograft survival, especially in the nontransfused patients, may perhaps be influenced more by the effective manipulation of immunosuppressive therapy during rejection episodes. (3) The presence of lymphocytotoxins per se may not have any deleterious effect on the survival of second allografts.


Bone marrow transplantation--present status.

In the short space of the last 10 years, marrow transplantation has become a reasonable treatment option for persons with severe aplastic anemia. It has not as yet convincingly established itself in the treatment of leukemia and other malignancies but shows promise with new approaches. Many of the immunologic problems generic to bone marrow transplantation have been identified, and solutions are actively being pursued in the clinic and at the laboratory bench. As solutions to some of the present-day obstacles to the full therapeutic potential of bone marrow transplantation are met, we should see, in the next 10 years, a wider application of this therapy to various hematologic and malignant disorders.


Successful bone marrow transplantation in sensitized recipients.

Fourteen patients with aplastic anemia and one with the Wiskott-Aldrich syndrome who were specifically sensitized against their donors were successfully engrafted with bone marrow from those donors. Sensitivity was detected in antibody-independent and antibody-dependent cell-mediated lysis assays. In order to erase this immunity to non-MHR familial transplantation antigens, multiagent immunosuppression with cyclophosphamide, procarbazine, and whole rabbit antithymocyte serum (ATS) was used. The data suggest that ATS was largely responsible for abrogation of this sensitivity and indicate that immunity does not represent a barrier to successful transplantation.


Cryopreserved autologous bone marrow transplantation in the treatment of selected pediatric malignancies: a preliminary report.

We have shown that it is possible to collect and viably store sufficient numbers of stem cells to hematologically reconstitute patients following marrow-lethal doses of chemoradiotherapy. While no current procedure can be guaranteed to eliminate clonogenic tumor from the bone marrow, the fact that hematopoietic stem cells capable of reconstituting the host can be obtained after intensive chemotherapy makes it possible to clear microscopic foci of tumor from the marrow prior to storage. Such patients are now included in our protocol. The initial treatment results indicate that, in selected circumstances, tumor in otherwise refractory patients can be eliminated or partially controlled by a single intensive pulse of chemoradiotherapy with severe but acceptable extramedullary toxicity. The fact that patients can be rescued from otherwise lethal myelotoxicity by the reinfusion of cryopreserved autologous bone marrow permits wider exploration of new, more intensive cytoreductive regimens in a variety of cancers.


The quality of life after liver transplantation.

The quality of life after liver transplantation ranges from poor to superior. The social and vocational outcome is dependent on the quality of homograft function and on the steroid doses necessary to maintain function. A good long-term prognosis is usually evident by 1 year postoperatively. The complete rehabilitation of so many patients has encouraged us to continue our efforts in this difficult field.


Gastrointestinal complications of hepatic transplantation.

In this series of 150 orthotopic hepatic transplants, clinically significant gastrointestinal hemorrhage occurred in 34 patients (23%). Five patients (15%) survived this complication. Enteric perforations occurred in 20 patients following 198 biliary-enteric procedures. Only one patient survived. Enteric perforations unrelated to biliary procedures fared only slightly better with one survivor among eight perforations. These results clearly do not warrant complacency. Modifications advocated are an aggressive diagnostic approach and early reoperation with establishment of extensive peritoneal drainage where necessary.


Diagnosis and treatment of acute cardiac allograft rejection.

Integration of data derived from immunologic monitoring techniques and endomyocardial biopsy currently permits more precise administration of immunosuppressive medications for the treatment of acute cardiac allograft rejection than was formerly possible, resulting in a substantially improved outlook for long-term survival. Indeed, the probability of survival for 5 years postoperatively of 50% exceeds that for several categories of cardiac patients currently undergoing other more common forms of heart surgery. The continuing demonstration of the potential for cardiac transplantation clearly warrants further application of this procedure for the treatment of appropriate patients with end-stage cardiac disease.


Heterotopic versus orthotopic heart transplantation.

Since November 1974, heterotopic cardiac transplants have been performed at this unit in preference to orthotopic transplants. A number of reasons have led us to prefer this technique, namely donor malfunction in the immediate postoperative period and during rejection; right ventricular failure of the donor heart in the orthotopic position in patients with pulmonary hypertension; the ease of patient management; and the use of the donor heart as a temporary method of cardiac support. Disadvantages are the later recognition of rejection and the difficulty in performing transvenous endomyocardial biopsies. The results are satisfactory giving a 1, 2, and 3-year survival rate of 62%, 58%, and 50%, respectively.


Mitigation of hyperacute rejection by antilymphocyte globulin (ALG).

In HR, primarily humoral immunologic factors trigger a sequence of events that finally destroys the transplanted organ. Unspecific trapping of WBC diminishes the RBF, especially in the first compartment--the cortex. Pretreatment with ALG is able to suppress this cellular participation partially, thus postponing the stop of RBF without preventing the influence of humoral factors on the graft. As shown by pathologic and functional criteria recorded for 8 hr, an exclusive measurement of total RBF does not reflect an inhibition of the course of HR.


Monitoring of rejection.

Rejection in non-identical pairs is both antibody- and cell-mediated. Measurements of CDC and LMC specific for the donor can be useful clinical tools in confirming rejection, detecting periods of likely rejection, and helping to predict responses to therapy. In particular, the LMC assay appears to have excellent temporal correlations with graft status. Rejection in the HLA-identical sibling transplant is directed against a non-MHC antigen, is cell-mediated, and can be typed for using CTL.


Antibodies to donor B lymphocytes and autoantibodies in renal transplantation.

A positive CDC B-lymphocyte XM is not deleterious to long-term graft outcome. A positive unfractionated CDC XM is not a contraindication to transplantation if the positive crossmatch is due entirely to anti-B-lymphocyte antibody. B-lymphocyte autoantibodies are common in hemodialysis patients, but may account for only a minority of positive B-lymphocyte XMs.


Delayed renal function and long-term cadaver renal allograft survival.

This study indicates that (1) ATN adversely affects long-term allograft survival but not patient survival, (2) in patients with delayed function the duration of ATN does not influence allograft survival, (3) ATN kidneys with good recovery (SCR less than 3.0) do as well as immediate-function kidneys, (4) poor recovery from ATN (SCR greater than 3.0) is associated with poor long-term allograft survival and may be the result of allograft rejection during ATN, since analysis of multiple characteristics at the time of transplantation failed to discern any difference between the good- and poor-recovery groups, and (5) there are no reliable pretransplant indicators of those kidneys that will never function or be in the poorly recovered group.


Bone marrow transplantation for correction of enzyme deficiency disease.

Mutant acatalasemic mice provide a prototype of congenital enzyme deficiency disease. Normal blood catalase levels were achieved permanently in congenitally acatalasemic mice by transplantation of bone marrow cells from congeneic normal catalasemic mice using relatively small numbers of cells following whole body irradiation. The increase in blood catalase activity was physiologically effective as demonstrated by the protection of the previously acatalasemic mice against the otherwise lethal effects of hydrogen peroxide injections. Bone marrow transplantation has the potential to provide a continuous source of some enzymes and may be applicable as treatment for certain congenital enzyme deficiency diseases.


Renal transplantation in patients with diabetes mellitus--revisited.

Sixty-one patients with end-stage renal failure due to diabetic nephropathy received 68 renal allografts from June 1970 to February 1978. Patient and graft survival results equaled those for nondiabetic patients, as reported by the Human Renal Transplant Registry (HRTR). Renal allografts from siblings or pretreated cadaver donors had a significantly longer survival time than did allografts from nonpretreated cadaver donors. It is concluded that renal transplantation with living related and pretreated cadaver donor kidneys continues to be the treatment of choice and is superior to other forms of treatment in the insulin-dependent diabetic patient with end-stage renal disease.


Renal transplantation in insulin-treated diabetics.

In our view, renal transplantation in the uremic diabetic patient is justified. Recipients should be selected with caution. Patients with both loss of vision and heart disease will only rarely benefit from renal transplantation. Living related donor should be preferred if possible.


Comparison of the immunologic reactions of arterial transplants in the arterial system and of venous transplants in the venous system using inbred strains of rats.

(1) Arterial transplants used as arterial replacements induce sensitization of the recipient in the weakly as well as in the strongly allogeneic systems (afferent limb). (2) Venous transplants used as venous replacements induce sensitization of the recipient (afferent limb). (3) Arterial transplants show increasingly severe rejection reactions paralleling the degree of immunogenetic difference (efferent limb). (4) Veins transplanted as venous replacements are tolerated even in the strongly allogeneic systems (efferent limb).


Gonadal function after renal allotransplantation.

Our data suggest that impaired testicular function was corrected, but not completely, by renal allotransplantation. One patient with impaired renal function showed azoospermia and six patients with normal renal function oligospermia. It was observed that conception might occur when the sperm count was below 10 million/ml. The elevated FSH among patients with azoospermia or oligospermia indicates a responsive pituitary. The positive clomiphene test suggests that the function of the hypothalamo-hypophysial axis is normal.


Influence of HLA-A, B, C, and D matching and pretransplant blood transfusions on kidney graft survival.

A significant influence of matching both for the HLA-A and B and the D/DR antigens on graft survival in patients transplanted with kidneys from living related or cadaveric donors is demonstrated. A generally reduced survival of cadaveric grafts during the last few years may at least in part be explained by the use of more three and four antigen-mismatched donors. The beneficial effect of pretransplant blood transfusions on graft survival in our material is almost nulled when uremic patients, dying while waiting for a transplant, are also considered. In addition, significantly more high-risk patients are included in the nontransfused patient group.


Effectiveness of a new drug, bredinin, on canine kidney allotransplant survival.

BR has remarkable effectiveness on canine kidney allograft survival. Its effectiveness in suppression of the immune responses is dependent on the dosage. Atrophy of the spleen and the mesenteric lymph nodes is prominent in treated dogs. Septic complications are slight, with no reduction in the number of peripheral white blood cells. Erosive changes of the mucosa in the entire bowel are the major side effects of the drug treatment. Liver functional abnormality has not been observed.


Prolonged kidney allograft survival with promethazine.

The effects of promethazine hydrochloride have been investigated in a rabbit kidney allograft model. The drug was ineffective on its own, but if added to a protocol that induced partial suppression of rejection in 50% of recipients, its effect was dramatic. Allograft survival was prolonged from a control mean of 10.3 days to a mean of 26.3 days. One animal survived 2 1/2 months, and no other drug than promethazine was given after day 6. Promethazine and 6-methylprednisolone alone also prolonged allograft survival, but the results were significantly better if the recipient had been exposed to donor blood before grafting. The results suggest that promethazine is a useful adjuvant immunosuppressive drug. It could be beneficial in man.


Dilutions and specificity analysis of pretransplant sera.

Six serial dilutions of 51 sera from pretransplant patients were reacted against T and B lymphocytes at 5 degrees C and 37 degrees C. By the use of defined panels of T and B lymphocytes it could be shown that 10% of the 51 positive sera contained T-warm antibodies against HLA-A, -B, and -C specificities. There were 28% of the sera that had antibodies against non-HLA antigens reactive to B lymphocytes in the cold. Other sera contained mixtures of HLA and non-HLA antibodies. By dilution analysis of the sera, the mixtures could be detected and the HLA specificities identified. This ability to distinguish between HLA and non-HLA antibodies should be important in classifying pretransplant patients into high- and low-risk patients. Prior evidence that we have presented suggests that the non-HLA antibodies may be enhancing antibodies.


Posttransplant hypersplenism.

Posttransplant hypersplenism, manifested by leukopenia and azathioprine intolerance, can be diagnosed with a high degree of accuracy and promptly reversed by emergency splenectomy. Functioning cadaver kidney homograft survival rates in patients undergoing posttransplant splenectomy are equal to that of patients undergoing pretransplant splenectomy and are statistically superior (p less than 0.01) to recipients who have never had their spleens removed. However, mortality (21%) for posttransplant splenectomy is excessively high when compared to our mortality (1.3%) for pretransplant splenectomy.


[Temperature-dependent structural rearrangements in the cytoplasmic membranes of Escherichia coli cells].

By the freeze-etching method, in has been shown that E. coli plasma membranes undergo a structural transition in the range of temperatures within 0 and 20 degrees C which could be observed as redistribution of intramembrane particles with free-zone formation. The onset of temperature interval of this transition (20 degrees) well correlate with the break in the Arrhenius curves characterizing the cell membrane permeability for free nucleotides and for respiration intensity.


[Intercellular information transfer in the process of immunogenesis. VI. The induction of antiphage antibody synthesis in the cells of rat transplantable lymphosarcoma under the influence of splenic RNA from rats and mice immunized with phage T2].

It has been proved that nuclear and cytoplasmic RNAs, isolated from spleens of T2 phage immunized rats and mice, can induce T2 phage antibodies in cells of the transplantable rat lymphosarcoma. With the nuclear RNA from rat spleens, the effect is persisting in a number of subsequent cell generations. The data presented are principally in accord with results of the authors' previous studies in which lymphosarcoma cells were treated with RNA extracted from spleens of rat immunized with sheep red cells. These results well compare with the authors' earlier advanced hypothesis suggesting a possible involvement of RNA in deblockation of genes responsible for the synthesis of the antibodies in question.


Double blind controlled comparison of aspirin, allopurinol and placebo in the management of arthralgia during pyrazinamide administration.

Chinese patients with arthralgia during treatment with an antituberculosis regimen containing pyrazinamide were allocated at random to 3 anti-arthralgia treatment series in a controlled double-blind study. One series (18 patients) received soluble aspirin 2.4 g daily, the second (23 patients) allopurinol 200 mg daily, and the third (19 patients) placebo only, for 8 weeks. The response was assessed both by independent assessors and by the patients themselves using a diary card. The serum uric acid concentration was measured before and during anti-arthralgia treatment. The joints most commonly affected were the shoulders, the knees and the fingers, and symptoms and signs were in general neither severe nor protracted. For most of the patients in all 3 series the joint symptoms and signs improved during the 8 weeks, but a higher proportion of patients in the aspirin and placebo series than in the allopurinol series experienced improvement, this being most rapid in the aspirin series. Only in the aspirin series was the mean serum uric acid concentration lower during treatment than before it, and this effect was related to the dose in mg per kg. It is concluded that the arthralgia was often self-limiting, that aspirin had a small beneficial effect, that allopurinol, in the dosage studied, may have had a slightly deleterious effect, but that it would be worth studying larger dosages of allopurinol because the dosage studied did not affect the serum uric acid concentration.


Importance of cystourethrography in neonates with imperforate anus.

Infants born with imperforate anus have a high incidence of genitourinary anomalies. Vesicoureteral reflux was the most common abnormality in this series. Since these patients often have bacteriuria, this is an important finding. An intravenous pyelogram and voiding cystourethrogram should be part of the evaluation of each neonate with imperforate anus. Persistent cloaca, a frequent finding in the female patients, may require special diagnostic attention.


[Replacement of postoperative total defects of the mouth floor, chin and lower lip with Filatov's pedicle flaps].

The plasty with Filatov's pedicle grafts was applied in 3 patients with postoperative defects of the oral cavity fundus, chin, lower lip, tongue and mandible. The author recommends to apply this method in the complex treatment of neglected forms of cancer of the oral mucous membrane.


[Tumors of the small intestine].

Peculiarities of the clinical picture, diagnosis and surgical treatment of the small intestine tumors are considered in the paper, as well as immediate and late results of the treatment. The results of the treatment of 14 cases of the small intestine tumors are summed up (6 benign neoplasms and 8 malignant ones). The authors have come to the conclusion that in the most of cases tumors of the small intestine remain symptom-free for a long time; not infrequently they are complicated with intestinal ileus, perforation of the tumor and  peritonitis. Resection of the portion of the intestine with tumors and of a segment of the mesentery with the removal of the enlarged regional lymph nodes provides an only radical method of the treatment. An original scheme of the small intestine tumors localization is set forth in the paper.


[Surgical treatment of varicose veins of the lower limbs].

146 patients with varicosis of the lower limbs were operated upon in a method unified by the author. Consideration was given to the late results found in 132 patients followed up within the period from 1 to 9 years. 5 patients (3.8%) developed recurrence of the disease.


[Theoretical grounds for free osteoplasty in suppurative infection].

From the materials of extensive experimental studies and clinical observations the theoretical grounds for the free bone plasty under the conditions of purulent infection were devised. The methods of investigation of the microcirculatory vascular bed, luminescent microscopy with a tetracycline mark, photometry, planimetry and other specific tests were applied. Findings obtained in earlier experiments on 2000 animals (rabbits and dogs) and data of supplementary special studies on 185 rabbits were used. It was found, that from the point of view of the condition of the microcirculatory bed and osteogenetic potentiatlities of the mother bone, the free bone plasty is quite grounded theoretically. The authors' theoretical postulates are supported by successful treatment of 47 patients with hematogenic spine osteomyelities, subjected to bone plasty of the defects formed after the removal of purulent inflammatory foci.


[Sutureless ultrasonic hermetic sealing of the bronchial stump after experimental and clinical lung resection].

The authors have shown the possibility of the hermetization of the bronchial stump after resection of the lung through the use of osteocyanacrlic mass treated with ultrasound. A small number of clinical reservations, however does not allow to recommend the method for a broad use in the clinical practice. Nevertheless the authors believe the idea of ultrasound sutureless closure of the bronchial stump to be a promising one and needing further studies.


[Treatment of acute pancreatitis].

The results of the treatment of 274 patients with acute pancreatitis are analysed. 221 patients were subjected to conservative treatment (mortality--5.4%) and 53 patients were operated upon (mortality--30%). The best results were obtained in conservative treatment with the use of fluorofur and fluorouracil (62 patients), which had no fatal outcomes.


[Contralateral donor kidney study for predicting the fate of transplants in the recipient body].

An analysis of clinico--laboratory findings concerning functional condition of cadaver donor kidneys in the recipient's organism and morphological changes in 12 contralateral donor kidneys is set forth in the article. It has been found that in a cadaver donor kidney an impairment or an arrest of the graft function may be due to various pathological processes present in the donor intravitally.


[Principles of the surgical treatment of combined lesions of the brachiocephalic and renal arteries in nonspecific aorto-arteritis].

The presented work is founded on the analysis of the results of the surgical treatment of 43 patients with combined injuries to the brachycephalic and renal arteries, manifested clinically as syndromes of cerebral ischemia and vasorenal hypertension. 50 operations were carried out upon 43 patients. 45 of these 50 operations were reconstructive ones. 6 patients were subjected to several-stages operations both upon the brachycephalic and renal arteries. 80% of the patients showed good long-term results. An active surgical tactics allowed to diminish dramatically the percentage of nephrectomy in non-specific aorto-arteritis.


The fertility of bulls born twin to freemartins: a review.

Evidence for the existence of XX germ cells in the testes of bulls born twin to females is reviewed. It is concluded that there is probably no shift in the sex ratio of the offspring in favour of females. Reports on the fertility of such bulls are reviewed. It is suggested that, provided the semen is normal, there is no reason why such a bull should not be used for breeding purposes.


A three-month study of environmental mastitis in a dairy herd.

During the autumn/winter of 1976, a study was made of a severe mastitis outbreak which occurred in a herd of 96 cows. Forty-four cows and 61 quarters were clinically infected with new infections between September and mid-December. Escherichia coli was isolated in 84 per cent of clinical samples submitted for bacteriological examination.


[Role of peroxidase in the pathogenesis of parodontosis].

In order to study the role of peroxidase in pathogenesis of periodontosis clinical observations were carried out in 132 patients with inflammatory-dystrophic form of periodontal disease and eight species of laboratory and domestic animals were used in experiments. In the patients studied a distinct increase in peroxidase activity was observed in mixed saliva and in gum tissues, which correlated with the severity of the periodontal disease. Inflammatory-dystrophic impairment of cat periodontium was accompanied by an increase in the peroxidase activity only in gum and alveolar process tissues; cats are characterized by the highest amounts of exogenous peroxidase in oral tissues as compared with other laboratory animals. High amounts of exogenous peroxidase did not affect the periododontal tissues of rats during long-term experiments. The main protective effects of the enzyme were as follows: bacteriostatic influence on streptococci in oral cavity and inhibition of leukocyte emifration. Estimation of the peroxidase activity in saliva may be considered as a diagnostic test for periodontosis and may be used to monitore the course of treatment.


[Express method of detecting mutant forms of human serum cholinesterase].

An express method is developed for detection of patients carrying dibucaine-resistant and "silent" variants of cholinesterase in blood serum. 200 donors as well as 25 patients with various with various pathological syndroms were examined; 5 patients carrying dibucaine-resistant cholinesterase were detected, which constituted 2.22% in the group. The method might be used in anesthesiology, blood transfusion and in experimental studies of the problems of medical genetics.


[Treatment of cholecystopathies by Fumaria nebulisate].

In 85 patients with cholecystopathies the therapeutic effect of the Fumaria-preparation Oddibil was tested. The therapy was successful alltogether in 70%, in dyskinesias of biliary tract in more than 80%. The optimal therapeutic result was obtained after 10 days on an average. The difference between the Fumaria nebulisate and a placebo with regard to the efficacy was statistically significant. The amphocholeretic effect of the praparation is especially to be emphasized. Side-effects didn't occur.


An early look at the therapeutic uses of some new vasopressin analogs in gastroenterology.

Natural vasopressins have been used, with varying success, in attempts to stop bleeding from esophageal varices for over two decades. Reasons for lack of success include (a) failure to induce a sufficiently prolonged and constant vasoconstrictor effect at the bleeding site, (b) dangerous side-effects, and (c) release of plasminogen activator induced by the peptides which can lyse any clot as it forms.IN THE LAST DECADE ANALOGS OF VASOPRESSIN HAVE BEEN DEVELOPED WITH A PROLONGED ACTION, USING TWO SEPARATE PRINCIPLES OF CHEMICAL MODIFICATION: (1) hormonogens, and (2) blockage of sites of inactivating enzymatic cleavage (in particular "carba" analogs without a disulfide bridge). These two categories of analog are compared here: the carba analogs have the advantages of high potency (higher than the parent hormone) with prolongation, but are also very active on the plasminogen activator release system. The hormonogens combine prolongation with low potency, but have lost not only a releasing action on plasminogen activator, but also, by virtue of altered release kinetics, have effectively lost cardiovascular toxicity.Mechanisms of analog action and receptor interaction are presented, along with initial clinical experiences.


Renovascular hypertension: pathophysiology, diagnosis, and treatment.

Renovascular hypertension can result from renal artery lesions involving the main renal artery, or its branches. It is generally felt that the elevation of blood pressure results from excessive systemic vasoconstriction secondary to enhanced renin secretion by one or part of one kidney. Renin secretion is enhanced because of constriction of the renal artery and resultant intrarenal ischemia. Clinically patients cannot be distinguished from those with essential hypertension and diagnosis must be made with arteriography although urography and isotope renography may suggest the diagnosis. Surgical cure can be predicted if differential renal vein renin ratios lateralize but a non-lateralizing study does not necessarily mean that surgery will fail. In properly selected patients, surgical results are excellent.


Studies on cholesterol ester formation and hydrolysis in liver disease: a selective review.

Plasma cholesterol esters are formed within the circulation by lecithin-cholesterol acyltransferase (LCAT), an enzyme produced by the liver. Patients with hepatocellular disease have low plasma LCAT activity. This largely accounts for the decreased levels of cholesterol esters observed in such patients and appears due to impaired hepatic production of the enzyme. In contrast, activity of the LCAT reaction in patients with cholestasis seems variable and is the subject of controversy, largely because the influence of abnormal cholestatic lipoproteins on the reaction requires further clarification.Human liver contains a lysosomal cholesterol ester hydrolase (CEH) which may play an important role in hepatic cholesterol homeostasis. In patients with liver damage there is no concrete evidence of circulating CEH activity, but recent studies show elevated activity of hydrolase within the liver itself in acute hepatitis. Hepatic activity of another lysosomal enzyme, acid phosphatase, is not increased, suggesting that high CEH in hepatitic liver does not simply reflect a general increase in lysosomal enzymes. The pathogenesis and significance of altered CEH activity in liver disease require further study.


The role of the liver in the adrenergic regulation of blood flow from the splanchnic to the central circulation.

Cardiac output is determined, in large part, by the venous return of blood to the heart. Various adrenergic and pharmacologic influences affect venous return. In the dog it appears that the liver may play an important role in the control of blood flow from the splanchnic to the central circulation and, hence, in the control of venous return.


The contribution of gut-derived endotoxins to liver injury.

The liver serves as the key organ for the removal and detoxification of bacterial endotoxins that are continously absorbed in small amounts from the gastrointestinal tract. This paper postulates that liver injury impairs this detoxification process leading to further liver damage and systemic effects as well. Evidence is reviewed to support the contention that endotoxin may be a major common pathway for liver injury by a variety of agents, and methods of reducing endotoxicity of gut origin are proposed. Finally, a new solid phase radioimmunometric assay for E. coli 026 is described and its usefulness as a gut marker suggested.


The etiology of chronic active hepatitis in Korea.

In a study of apparently normal, healthy Korean Army recruits performed in 1962, we found that 42 of 1,906 screened subjects had elevations of their serum glutamic pyruvate transaminase. Liver biopsies were obtained from 32 of these subjects and 9 of these had a "novel" antigen present, which reacted specifically with a convalescent serum from a case of serum hepatitis. We have recently tested frozen serum obtained from 8/9 of these cases and found that all 8 had HBsAg in their serum which, in some cases, persisted for at least three months. We reviewed the histological specimens from the original 32 cases using newly defined criteria: 18 were diagnosed as chronic active hepatitis and the 8 HbsAg positive cases with the "novel" antigen were in this group. In four of these cases the lesion appeared to progress to cirrhosis during a 3--4 month follow-up period. Since none of the cases had a prior history of hepatitis and no symptoms developed during the follow-up period, our findings emphasize the significance of chronic hepatitis B virus carrier state in the etiology of cryptogenic cirrhosis.


Apprentices in trouble: some problems in the training of surgeons and apothecaries in seventeenth century London.

Mayor's Court interrogatories and depositions in six disputes between apprentices and their surgeon and apothecary masters in London in 1654-1684 are reviewed. Evidence is presented to illustrate aspects of the operation of the apprentice system.


Glucose-6-phosphate dehydrogenase deficiency and infection: a study of hospitalized patients in Iran.

The Mediterranean variant of glucose-6-phosphate dehydrogenase (G6PD) is functionally deficient and found in a variety of cell types of affected individuals, including both erythocytes and neutrophils. To determine if the presence of this sex-linked gene is associated to any degree with the occurrence of severe bacterial infection, a study of hospitalized male patients in Iran was undertaken. As determined by erythrocyte assay, allele prevalence in male patients with infection was 22% vs. 12% in a patient group matched for the absence of other risk factors for infection and 6% in a second group who had additional risk factors for infection. When the control and patient groups were considered together the difference between the frequency of G6PD deficiency (10.2%) was significantly different from that found in the infected patients (p less than .05). Furthermore, the mean age of infected patients with G6PD deficiency was significantly less than that of infected patients without G6PD deficiency or non-infected control groups. These data suggest that host defenses may be altered in G6PD deficiency so that bacterial infections are more severe. Alternatively, G6PD deficiency and infection might represent concomittant risk factors which lead to hospitalization during bacterial infection. Potential mechanisms by which host defenses might be altered in G6PD deficiency are discussed.


[Experimental reconstructive surgery of the common bile duct (author's transl)].

In reconstructive surgery of the common bile duct the exact everting adaptation--by microsurgical suture technique--was studied in 4 male bastard dogs. This operative procedure is followed by minimal amounts of granulation tissue in region of the anastomosis. In contrast to the synthetic Teflon material the bovine heterograft (Solcograft) did not satisfy as choledochal substitute. In spite of precise suture technique the inner surface of the graft was not covered with epithelium of the biliary tract one year later.


[Peripartal and puerperal infections as reflected in articles in the Zentralblatt für Gynäkologie from 1878 to 1978].

Historical review about puerperal infections in the last 100 years on the background of publications in the Zentralblatt für Gynäkologie. The time was divided in three parts: The time after Semmelweis (1878 to 1920), the first time of chemotherapy (1920 to 1940) and the antibiotic epoche (after 1940).


[Purification and physico-chemical analysis of the fimbrial antigen in two different genera of Enterobacteriacea: Salmonella enteritidis and Yersinia enterocolitica (author's transl)].

Chemical, physical and immunological properties of the fimbrial antigen of two different genera of Enterobacteriaceae, namely Salmonella (S. enteritidis) and Yersinia (Y. enterocolitica) were analysed. Only a few strains of these two bacterial genera possess a fimbrial antigen which proved to be identical in all tests. Purified fimbriae are unstable in buffer solutions. They tend to form aggregates, patterns of which are between 240000 and 270000. Submitted to solubility testing by various methods these aggregates easily dissociate into particles of different molecular size. Treatment with 1% sodium dodecyl sulphate (SDS) in 1% mercaptoaethanol at 37 degrees C for 60 minutes gave constant reproducible results. The fimbrial protein prepared by this method proved to be an antigenically active unit with a molecular weight of 23450 for S. enteritidis and 23350 for Y. enterocolitica. The electron microscope revealed that purified fimbriae of these two genera consist of extremely thin filaments (1.5 to 2.7 nm), covering the bacterial cell as an envelope. They are supposed to be composed of no more than 2 to 3 peptid chains. The presence of the amino acids tyrosine, phenylalanine and tryptophane may be responsible of the particular behaviour of the fimbriae which according to different external conditions react with different states of dissociation. Probably the filaments are not stable in a solution as single filaments but tend to form oligomer, secondary and tertiary structures. Experiments of isoelectric focusing revealed that both antigens consist of a pure protein component (composed of 17 amino acids) which appears at pH 3.9.


[Enteritis due to Escherichia coli O142 K86 H34 in a ward of premature infants. With a discussion on the problem of pathogenicity of "enteropathogenic serogroups of E. coli" (author's transl)].

E. coli O142 K86 H34 has been isolated from stool specimens of five babies in a ward of premature infants. Diarrheal stools were observed in two of them; one infant temporarily failed to gain weight, and the other developed a temporary loss of weight. Smooth stools observed in the third baby as well as asymptomatic infections in two others did not affect their normal development. The outbreak lasted 15 days; the source of infection and the mode of transmission remained unknown. The pathogenesis and importance of human diarrheal disease caused by E. coli is reviewed. Enteritis of adults and children due to enteroinvasive (EIEC) and enterotoxigenic (ETEC) strains is described. The etiological role of so-called "enteropathogenic E. coli" (EPEC), rejected increasingly during the past decade, has been demonstrated again in recent studies. Routine search for EPEC is suggested in cases of infantile enteritis in hospitals and other institutions.


[A fi- tetracyclin resistance plasmid with specific restriction of phages on salmonella typhi, S. paratyphi B and S. typhi-murium (author's transl)].

Among 262 strains of Salmonella typhi from an epidemic outbreak of typhoid fever in Baden-Württemberg in 1974 2 strains were isolated which were tetracyclin resistant and showed no reactions with the Vi testphages T, D6 and VII whilst all other strains belonged to lysotype A, subtype Tananarive. It turned out that the Tc resistance in both strains was caused by a fi- R plasmid which could be transfered to other S. typhi strains, to E. coli K12, S. paratyphi B, S. java and S. typhi-murium as well as from Tc resistant E. coli K12 back to S. typhi. The Tc R plasmid introduced in S. typhi, lysotype A, caused specific restrictions of typing phages T, D6 and VII. Also, the transfer of the plasmids to strains of S. paratyphi B and S. typhi-murium resulted in restrictions of a number of typing phages. Both plasmids had identical patterns of restriction. In this pattern the Tc R plasmid differed from those described in the literature.


The antibody response to enterobacteriaceae and pseudomonas of patients with malignancies complicated by bacteremia.

The antibody response to the O antigens of the patients' own gram-negative bacteria causing bloodstream infection in patients with malignancies was investigated using the hemagglutination test. Of the 87 patients, 42 (48%) produced specific antibodies in significant titers. Differences were noted between the various microorganisms. Of 44 patients with E. coli bacteremia 26 (59%) had an antibody response, whereas only 5 (33%) out of 15 subjects with Pseudomonas aeruginosa infection did. The antibody response of patients with solid tumors (61%) was significantly better than that of subjects with RES malignancies (30%). Documentation of the humoral immune response of patients to isolates from blood cultures excludes laboratory contamination and supports the relevance of the isolated microorganisms. Thus, for diagnostic purposes documentation of the immunoglobulin response supplements bacteriologic findings.


[Microcalorimetric testing of the antibacterial activity of doxycycline, gentamicin and their combination (author's transl)].

The antibacterial activity of doxycycline and gentamicin was tested by microcalorimetric methods and by finding out the MIC of these substances, the test organisms being Staph. aur. haem. (13.665) and E. coli (3.579). The investigations were carried out with the above mentioned substances both alone and in combination. A synergistic effect was found with both methods applied, but microcalorimetry showed that the combination influences the cell metabolism in another way than the individual substances. Another remarkable finding is that doxycycline inhibits the microcalorimetric activity of our bacterial strains in doses 10 to 100 times lower than found with the standard MIC finding methods.


[Antilymphocyte immunoglobulin with an associated antibacterial directed effect. II. The use of the preparation in the overall therapy of chronic lympholeukemia].

Use in the composition of complex therapy of patients suffering from chronic lympholeukemia of antilymphocytic immunoglobulin with an associated antibacterial activity aided normalization of the leukocytic differential count and prevented development of inflammatory and septic complications in these patients.


[Patterns determining the dynamics of the epidemic process in Sonne dysentery and its relation to the type of causative agent].

The results of studying the dynamics of the epidemic process of dysentery, based on the data from 3 districts of Moscow, are presented. The study revealed the periodicity of 3 years in the course of the epidemic process of dysentery, occurring against the background of a considerable predominance of Sh. sonnei, biochemical type 2. The use of the cohort method for analyzing the age structure of dysentery cases showed the possibility of using this method to find out to what extent the epidemic process repeatedly affected the same groups of population.


[Comparative characteristics of conglutination and immunoconglutination reactions and their participating constituents].

The difference between the hemolytic and conglutinating properties of equine complement was shown by the method of conglutinin and immunoconglutinin titration in the author's modification. Different localization of conglutinating antibodies (in the supernatant fraction) and conglutinins (in the sediment) in bovine serum was revealed by the method of serum fractionation in the stream of carbon dioxide. The differences in the localization of conglutinins and immunoglutinins (in the sediment and the supernantant fraction respectively), as well as the differences in the localization of hemagglutinins and conglutinins in the sera (in different fractions) were determined.


[Analysis of merodiploid strains of Sh. flexneri that have lost virulence].

Episome F'13 introduced into the genome of a virulent Sh. flexneri strain brought about changes in a number of properties of the recipient strain. The expression of these properties was not connected with the chromosome area allelic to the plasmid genome. These changes seem to be induced by the mobilization of the chromosome genes of E. coli. The loss of virulence in Sh. flexneri strains carrying episome F'13 seemed to be the consequence of two reasons: the overlapping of kcpA gene by its dominant avirulent allele and abnormal synthesis of cell wall lipopolysaccharide due to the transfer of the mobilized genes from the donor strain F'13. When the preliminary mapping of genes on the chromomome was made with the use of plasmids, it was found necessary to use F-episomes which had no influence on the changes occurring in the phenotypic characteristics of the recipient.


[Search for host specificity systems in Shigella using DD-series phages].

A total of 712 Shigella strains were studied with the use of dysentery diagnostic phages DD II, DD VI and DD VII in order to reveal the systems of host DNA specificity. The study comprised 4 tests: mass screening by the intensity of phagolytic reaction of phages in various strains; and the determination of the parameters of adsorption. As a result, an effective modification and restriction systems were revealed in Sh. sonnei 311 with the use of phage DD II. Bacteriophage DD VII was effectively restricted in E. coli CK, BB and BB/T4. Cross titration showed that the modification and restriction systems of E. coli BB and BB/T4 differed from the specificity system of E. coli CK. Phage DD VI had an exceptionally broad spectrum of activity and was not sensitive to any known restriction system.


[Significance of the ability of E. coli to alter capillary permeability for the reproduction of pyelonephritis in mice].

Experiments in a number of biological models showed that the cultures of E. coli isolated from the urine of children with pyelonephritis had a varied spectrum of pathogenic properties. Histologically confirmed pyelonephritis induced by intravenous infection in CBA mice, treated with 5% glucose by the method of Montgomerie et al., correlated with the bacterial adhesiveness to the epithelium and the interference with capillary permeability, registered in experiments on the pulmonary model with Evans blue used for control. The criterion for the development of pyelonephritis in mice, which was based, in the opinion of Mintogemerie et al., on the positive results, indicating the presence of the infecting agent in the culture obtained by inoculation with the samples of urine and kidney tissue, was found to be insufficient, as only 28 out of 45 cultures of E. coli isolated from the kidneys coincided with histologically confirmed cases of pyelonephritis.


The regulatory cysK mutant of S. typhimurium.

A triazole-resistant mutant, cysK1358, showing novel properties was isolated. Biochemical analysis of this strain suggests a regulatory character of the cysK1358 mutation. The cysK1358 mutation has a pleiotropic effect: the expression of the other gene, cysA, is also altered.


Evaluation of the gonadotrophic responsiveness of the pituitary to acute and prolonged administration of LH/FSH-releasing hormone (LH-RH) in normal females and males.

In normal females, the injection of 25 microgram of LH-RH (acute test) induced a greater LH and FSH release from the pituitary in the mid-luteal than in the mid-follicular phase of the menstrual cycle. In normal males, the responsiveness to 25 microgram LH-RH was greater than that in females at mid-follicular but not at the luteal stage. The pituitary response to the prolonged LH-RH infusion (0.21 microgram/min/8 h) was similar in both phases of the cycle of the females with a decline in serum gonadotrophins after the 4th hour and was paralleled by a significant increase of plasma oestradiol levels. In males the LH, but not the FSH secretion was lower as compared to female subjects, and gonadotrophin levels did not show a fall during the infusion. The acute injection of 25 microgram LH-RH at the end of a prolonged infusion induced the same response in the female subjects in both phases of the cycle. In males, the acute test following prolonged infusion produced a similar LH secretion, but a lower FSH response than in females. The comparison of the acute test alone and that preceded by a prolonged LH-RH infusion, demonstrated that, in females, the only significant differences consisted of a greater LH secretion in the former test in the mid-luteal phase. In males there was greater FSH secretion in the acute isolated test than when this test was given after the prolonged infusion.


The plasma FSH and LH response to synthetic LH-RH in normal pre-pubertal and early pubertal girls--a re-evaluation.

A standard LH-RH test (50 microgram/m2) given iv was carried out in 65 normal girls, 42 of them pre-pubertal aged from 4 7/12 to 11 years and 23 in the early stage of puberty, aged from 9 to 12 9/12 years. The results indicate that in pre-pubertal girls the basal levels of the plasma gonadotrophins remain steady (LH 0.6 +/- 0.1 mIU/ml; FSH 0.8 +/- 0.1 mIU/ml, m +/- SD) and that there is a small but significant response of LH to LH-RH (1.6 +/- 0.2 mIU/ml). During this period the FSH response to LH-RH is very marked (8.0 +/- 1.0 mIU/ml) with a gradual, significant decrease seen towards the onset of puberty (6.5 +/- 0.9 mIU/ml, P less than 0.001). These results support earlier reports that the LH-RH test is a useful tool to evaluate the secretion of pituitary LH and FSH in early childhood.


Growth impairment with elevated somatomedin levels in children with chronic renal insufficiency.

In children with chronic renal insufficiency serum levels of somatomedin measured by radioreceptor assay were found to be strikingly elevated and were in the same range as in acromegaly in spite of decreased growth. The serum somatomedin level was inversely correlated with renal function and children on haemodialysis had the highest values. The elevated somatomedin was most likely due to progressive destruction of the kidney, the primary catabolic site for somatomedin and other polypeptides. After successful transplantation the somatomedin values fell to slightly above normal even though growth was still impaired. Using a bioassay based on the mitogenic property of somatomedin, a lower than normal rather than an increased level was found in chronic renal insufficiency suggesting that in uraemia an inhibitor to somatomedin bioactivity was present. It is concluded that the cause of the growth failure in chronic renal insufficiency and after transplantation is not due to a lack of somatomedin, but an inhibitor to its action could be a factor. It would appear that a normal somatomedin may be necessary for normal growth, but it is not sufficient.


Comparison of one daily injection of NPH and crystalline PZI insulins on urinary glucose in diabetic children.

Two one-injection insulin regimens--a combination of intermediate-action NPH insulin with regular insulin and a combination of long-acting PZI insulin with regular insulin, all of porcine origin and manufactured by Nordisk Insulin Laboratories--were compared to a group of 10 juvenile diabetics, each child serving as his own control. The results of thrice daily urine tests were recorded for periods of 3 months during each regimen and the incidence of glucosuria of less than 1% constituted the index used for metabolic control. Although the total insulin dose was almost the same with both schemes, it was found that less glucose was excreted during the night and early morning with the PZI regimen than the NPH regimen, indicating that a single injection of NPH is insufficient for good diabetic control.


[Drug therapy of hyperprolactinemia and acromegaly].

Hyperprolactinemia can be treated medically. Thus all patients with a normal sella turcica and those patients with only slight enlargement of the sella turcica can be treated medically with the dopaminagonist bromocriptine. This treatment is also indicated in paitents with postoperative persisting hyperprolactinemia. In contrast to hyperprolactinemia medical therapy of acromegaly is still in the experimental stage, through the dopaminagonist bromocriptine induces a decrease of growth hormone levels and improvement of the disease in many patients with acromegaly.


Calcium antagonists and islet function. IX. Is extracellular calcium required for insulin release?

The physiological relevance of extracellular Ca2+ and Mg2+ to the process of glucose-induced insulin release is examined in both the isolated perfused rat pancreas and rat isolated pancreatic islets. When no Ca2+ is added to the perfusion or incubation media, both the initial and late phases of insulin release are severely impaired. The effect of Ca2+ deprivation is an immediate and immediately reversible phenomenon, although the length of the period of Ca2+ deprivation prior to stimulation with glucose modulates the severity of the impairment in the secretory response. When Mg2+ is omitted from the media, the response to glucose occurs precociously and at a higher than normal rate, such a facilitation being a rapid phenomenon. When both Ca2+ and Mg2+ are removed from the extracellular milieu, the secretory response may occur in a normal fashion, except for an earlier onset. The rate of secretion is only reduced after or during a prolonged exposure of the endocrine pancreas to media deprived of both Ca2+ and Mg2+. The release of insulin evoked by glucose in the absence of Ca2+ and Mg2+ is enhanced by theophylline, partially inhibited by verapamil, and abolished by the Ca2+-chelator EGTA. It is concluded that Mg2+, in physiological concentration, exerts an inhibitory effect upon the process of glucose-induced insulin release. However, even in the absence of extracellular Mg2+, the secretory process remains apparently dependent on the availability of minute amounts of extracellular Ca2+.


[Pathogenesis of hyperthyroidism].

The present concept for the etiology of thyroid disease permits the definition of three separate entities occuring with hyperthyroidism: Graves' Disease, Toxic Nodular Goitre, Autonomous Adenoma. Physiopathological properties of these entities lead to a rational therapeutic strategy for each one of them.


[New viewpoints on the pathogenesis of diabetes mellitus].

Diabetes mellitus is a syndrome characterised primarily by an increase in blood glucose and an absolute or relative deficiency of insulin. Etiologically, it is a complex disorder because many different genetic, environmental, immunological, metabolic and hormonal influences interact to produce the clinical picture diabetes. By introducing HLA typing in diabetes research in the last four years, it became possible to clearly distinguish between the juvenile-onset, insulin-dependent type and the non-insulin-dependent, maturity-onset type of diabetes mellitus. On the basis of this and other evidence, at least five nosologically distinct types of diabetes can be identified.


[Endocrine pancreas function and diabetes mellitus].

Carbohydrate metabolism is regulated by the anabolic action of insulin and by the catabolic effect of glucagon. Catabolic actions predominate in diabetes mellitus. Somatostatin exeits a diabetogenic action by inhibition of insulin release. The physiologic role of pancreatic polypeptide is unknown.


[Somatostatin].

Somatostatin, under physiological conditions, is a regulator of thyroid stimulating hormone, growth hormone, pancreatic islet-cell hormones and gastrin. In pharmacological dosage, gastric acid output, splanchnic blood flow and plasma renin levels, are influenced. A possible therapeutic effect on increased growth hormone secretion, disturbances of carbohydrate metabolism, gastroenteropathies and renal hypertension, is discussed. The clinical application is limited by the short biological half-life of the substance and the unspecific action on several organs.


FPL 57787 and migraine prophylaxis. A double-blind cross-over study.

In a double-blind cross-over trial with placebo, FPL 57787, a chromone derivate, was tested on 15 patients as a prophylactic against migraine. There was found to be no effect.


Transfer of bromocriptine across the blood-brain barrier in man.

The transfer of 14C-bromocriptine across the blood-brain barrier was studied in 10 patients using the double indicator single injection method. The extraction (E) of bromocriptine was 8 % (quartiles: 6 and 14 %). Based on the results the cerebral uptake velocity of bromocriptine was calculated assuming constant arterial drug concentration. Its T 1/2 was found to be 12--24 minutes, depending on the tissue-blood partition coefficient.


Intracranial aneurysms.

The modern history of the management of intracranial aneurysm encompasses little more than a quarter century. These are seen in 5% routine autopsies and those under 2 mm exist in 17% normal adult brain vasculature. One third of strokes are SAH and aneurysms account for 70% of these. Aneurysms rupture at a rate of 12/100.000 population/year, mostly on the 5th, and 6th decades. Given the high morbidity and mortality of these (43% from first haemorrhage if untreated), surgeons can attempt to avoid rebleeding for a week or more until surgery becomes safe and expand the ability to deal safely with most of them regardless of size or position. Early surgery has still an unacceptable morbidity and operation is usually planned between the 6th and 10th day after the first bleed. Early surgery is only indicated when there is a clot and deterioration. Conservative measures are reduction of blood pressure and use of antifibrinolysins and some minor surgical means whose practicality is still unknown. The recognition of warning leaks must be one of the significant factors for future treatment. Several surgical adjuncts are of considerable value, i.e., brain shrinking agents, microsurgical technique, induced hypotension. Aneurisms are classified as: small (less than 12 mm) large or bulbous (12-25 mm) and giant (greater than 25 mm). From 326 of small vertebral-basilar aneurysms the results were excellent in 246, good in 35, poor in 26 and 19 died. From 71 basilar aneurysms only 6 died, the results being excellent in 42, good in 10 and poor in 13. The management of giant anterior circulation (Table III) and posterior circulation (Table IV) aneurysms, involved various surgical procedures including carotid, middle cerebral, vertebral and basilar artery ligation, neck occlusion, wrapping or coating, as an overall result the outcome was good in 52 out of 63 gicunt anterior circulation giant aneurysms but was bad in 48 out of 91 posterior circulation giant aneurysms. The best results were obtained with 7 carotid-cavernous aneurysms (all good) and the worse results with 17 giant aneurysms of the basilar trunk at the superior cerebellar artery (11 poor, 6 good). A technique for the percutaneous occlusion of the basilar artery with a plastic Rommel type tourniquet is described (Fig 3). This allows the occlusion under local anesthesia. It has been used in 10 cases with 2 deaths STA-MCA by-pass proved to be useful for the progressive occlusion of the MCA in 3 cases of giant middle cerebral aneurysms.


Effects of lithium on morphological characteristics of dissociated brain cells in culture.

Lithium chloride was added in 5 and 10 mM concentrations for different periods of exposition time to dissociated cultures obtained from chicken embryonic brain. When supplementing lithium at day 1 in vitro for five days, a dose-dependent decrease in total protein was observed in the cultures as compared to the sodium-treated controls. Profound reduction was revealed in the length of neuronal processes and in the number of neuronal cell bodies by phase contrast microscopy and by morphometric means. After exposition of lithium in 10 mM concentration for 48 h, beside a slight decrease in number of perikaryons, a marked reduction in process length of neural elements was observed in the 6-day-old tissue cultures. Ultrastructurally, swollen and degenerating nerve processes have been found after lithium treatment suggesting a particular sensitivity of these structures to lithium ion.


Ripening of the cervix by intracervical application of PGE2-gel before termination of pregnancy with dilatation and evacuation.

In a randomized double-blind study a viscous gel, containing 0.25 mg prostaglandin E2 (PGE2-gel) or without prostaglandin (placebo gel), was applied intracervically in twenty-two nulliparous patients just before termination of early pregnancy by dilatation and evacuation (D & E). Within twelve hours a marked ripening of the cervix was found in all the eleven patients receiving PGE2-gel. Thus, a significant change in cervical dilatation from mean 5.4 mm to mean 10.7 mm occurred. Furthermore, a considerable softening of the cervix was registered. In the eleven patients receiving placebo gel, no significant changes in cervical dilatation or consistency were found. The subsequent D & E was easily performed in all patients treated with PGE2-gel. However, in three of the patients given placebo gel, D & E was difficult to carry out because of an unfavorable cervical state. To eliminate or decrease myometrial activity the calcium antagonist nifedipine was given orally to eight patients at application and five hours after application of 0.25 mg PGE2-gel. None of the patients recognized uterine contractions. However, also in these patients significant changes in cervical consistency and dilatation occurred within twelve hours. No side effects of the treatment were observed. It is concluded, that a preoperative, intracervical single application of 0.25 mg PGE2 seems to be useful to ripen the unfavorable cervix before subsequent termination of early pregnancy by D & E.


A new gel for intracervical application of prostaglandin E2.

A new gel-formulation for intracervical application of prostaglandin E2 (PGE2) has been prepared. As a vehicle for the gel a cross-link starch polymer is used. PGE2 substance is added to the starch polymer and after homogenization and lyophilization a PGE2 powder is obtained. The powder can be stored at room temperature for more than four months without inactivation of the prostaglandin. Before clinical application a few ml of saline is added to the powder giving, within 30 seconds, an easily-handled ready to use PGE2-gel. Chemical analysis by spectrophotometric technique reveals that the amount of unchanged PGE2 is the same in the new gel-formulation as in a conventional cellulose gel. In a randomized double-blind study the new PGE2-gel was intracervically applied to twenty nulliparae before abortion by dilatation and evacuation (D & E). Ten women were given a gel containing 0.25 mg PGE2 (PGE2-gel) and ten a gel without PGE2 (placebo gel). It was found that the PGE2-gel, in contrast to the placebo gel, produced a rapid ripening of the cervix facilitating the subsequent D & E. No adverse systemic or local reactions were found during or after the treatment.


Indoleamine accumulating neurons in the retina of chicken and pigeon. A comparison with the dopaminergic neurons.

Recently a special group of indoleamine accumulating neurons has been described in the retina of some mammals and goldfish. These neurons are characterized by their ability to accumulate indoleamines, whereby they become visible in the fluorescence microscope. They do not show any spontaneuos fluorescence. The indoleamine accumulating neurons are in this study shown to be present in the retina of chicken and pigeon. Their cell bodies differ from the earlier described cell bodies of the same type in other species in being larger and bottle shaped instead of round or oval, and in being situated further cutwards in the inner nuclear layer. Their terminals ramify in three sublayers in the inner plexiform layer. No indoleamine containing neurons could, however, be seen to fluoresce in normal retina of chick embryos, newborn chicken, older chicken or pigeons.


Early postoperative changes in graft thickness after penetrating keratoplasty. Influence of host corneal disorder on time course.

In 172 patients the thickness of the corneal graft was followed with frequent measurements during the first 14 days after operation. Three different graft thickness time courses were observed. Patients with keratitis, stromal dystrophy and corrosion or mechanical lesion showed a secondary rise in graft thickness on the 6th postoperative day, while patients with keratoconus and those treated with tranexamic acid showed no rise on the 6th day. Patients with Fuchs' dystrophy differed from the other groups in not reaching the maximal thickness until the 3rd postoperative day. The possible correlation of these three time courses with changes in the fibrinolytic system is discussed.


Mastoid obliteration.

Mastoid obliteration is recommended as a routine procedure in all mastoid surgery. Bone chips from the mastoid tip, bone paté from the cortical bone and lyophilized dura can all be employed effectively to fill the epitympanic space and Traumann's triangle. The former annulus is reconstructed using lyodura and periost-bearing bone and the canal wall is fortified and the cavity filled with the metally based postauricular musculoperiosteal flap. Any remaining cavity is filled with bone chips and bone paté.


Lymphocytes of adenoid tissue.

Adenoid tissue was obtained at operation from 27 children admitted for adenoidectomy and from 6 controls. The occurrence of cells with cytoplasmic immunoglobulin was studied semiquantitatively by immunofluorescence microscopy of tissue sections, by which localization, number of cells and class of immunoglobulin were determined. No differences were found between patients and controls. Cells isolated from adenoid tissue were compared with mononuclear leukocytes obtained from the blood. More B lymphocytes were found in the tissue, in particular IgM-carrying cells. This was more pronounced in the patient group. Cells were stimulated in culture with polyclonal activators and microbial antigens. The response of adenoid lymphocytes to Haemophilus influenzae (HI) was high in 7/27 patients; all patients in whom throat culture was positive for HI were low responders.


Immunoglobulin-producing cells in clinically normal, hyperplastic and inflamed human palatine tonsils.

Patients suffering from recurrent tonsillitis (RT), hyperplastic tonsillitis (HT), or idopathic tonsillar hyperplasia (ITH) were compared in immunological studies with subjects showing clinically normal tonsils. Serum concentration of immunoglobulins, particularly IgG, were found to be increased in association with tonsillitis. Conversely, the number of IgG-, IgA- and IgM-producing immunocytes per tissue unit was reduced in the germinal centres of lymphoid follicles, in the extrafollicular areas, and in the reticular parts of the crypt epithelium. The overall percentage distribution of these cells was normally 65:30:3.5:1.2 for the IgG, IgA, IgM and IgD classes, respectively. In RT these figures were 53:39:4.7:4.4; in HT, 67:25:4.0:4.5; and in IHT, 50 : 33 : 7.2 : 10. Thus, there were only small alterations in the immunocyte class proportions, except for a significant relative increase in IgD-producing cells. The results indicate that there is a functional defect of the tonsils in association with disease. The relative accumulation of IgD cells is probably explained by an inadequate local maturational process in B-cell system, altough some influence of low age cannot be excluded in the HT and ITH groups.


Immunohistochemical studies on the epithelial and lymphoid components of Warthin's tumour.

The lymphoid and epithelial elements of three Warthin's tumours (adenolymphomas) were studied by immunohistochemical technique. All classes of immunoglobulin (Ig)-producing cells were found, except IgE immunocytes. The numbers of cells/mm2 section area (median and range) were: 20.4 (15.2--27.2), 4.8 (2.8--12.4). 4.8 (0.4--9.6) and O (0--1.2) for IgG-, IgA-, IgM- and IgD-producing cells respectively. This gives percentage class ratios (68:16:16:0) which are quite different from those found in normal parotid tissue (3.6:91:3.1:2.6). Thus, the immunocytes found in Warthin's tumour are clearly polyclonal and show a class distribution comparable to that of lymphoid organs such as the tonsils. Also as in such organs, there were lymphoid follicles with mantle zone of B lymphocytes bearing membrane-bound IgM and IgD, and germinal centres showing reticular IgM staining. Apical staining for IgA and secretory component (SC) was shown in the luminal cells of the tumour epithelium, giving a fluorescence pattern similar to that of normal striated ducts. Selective transport of IgA apparently taken place into the cystic spaces of the tumour. Carcino-embryonic antigen (CEA), normally absent from striated ducts, was not generally present in the tumour epithelium, but was found in small groups of cells, especially in papilliferous parts of the epithelium. Warthin's tumour therefore seems to be composed of a fairly inactive normal lymphoreticular tissue and a neoplastic duct epithelium, most of which is highly differentiated with retention of immunoglobulin transport.


Heredo-ataxia and cochleo-vestibular disorders.

Cochleo-vestibular dysfunction of patients suffering from a heredo-ataxia, have been frequently described. A family and a single case are presented, which show the association of a heredo-ataxia, more specifically the Roussy-Lévy syndrome, progressive sensorineural loss, nystagmus and vestibular a- or hyporeflexia. A review of the literature is included and the standpoints concerning the nosological entities are discussed.


Masugi nephritis in T cell-depleted state. Influence of adult thymectomy and anti-thymocyte serum.

The effects of surgical removal of the thymus or the administration of antiserum to thymus-derived lymphocytes on the development of Masugi nephritis were investigated in Wistar rats. While thymectomy at weaning (ATx) had no significant effect on the humoral antibody response to injected rabbit IgG, repeated injections of rabbit anti-rat thymocyte serum (ATS) suppressed it remarkably. Both treatments did not show morphological evidences that glomerular inflammation and injury were suppressed in the autologous phase of Masugi nephritis. Glomerular lesions in rats receiving the nephrotoxic serum (NTS) one month after ATx (ATx-1+NTS) appeared to be severer in hypercellularity, mitotic counts, the amount of deposited fibrin-related substances and crescent formation than those in other nephritic groups. Morphological study of ATS+NTS rats revealed that the glomerular changes were nearly equal to those of NTS-injected control rats, in spite of markedly suppressed humoral response to injected rabbit IgG and the absence of host IgG along the glomerular capillary walls.


Widespread eczema vaccinatum acquired by contacts. A report of an autopsy case.

A 4-month-old male infant predisposed to allergic dermatitis acquired wide-spread eczema vaccinatum by contacts with a recently vaccinated sibling. He died of acute purulent peritonitis following a perforation of multiple duodenal ulcers. Fluorescence immunocytochemical and electron microscopic studies on the skin lesions revealed the presence of viral antigens and numerous virus particles compatible morphologically with those of the mature form from the same batch of smallpox vaccine given to the sibling. A large number of virus particles in the developmental form were also predominantly scattered in the cytoplasm of cells at the stratum malpighii of the epidermis as well as in neutrophils and macrophages in the skin lesions. The virus isolation from the skin lesions was done by using the HeLa cells and the human embryonic lung fibroblasts. No abnormal laboratory data were noted in immunoglobulins. On the basis of atrophy of the thymus and other lymphatic tissues and an appearance of large pyroninophilic cells in association with blastoid transformation, the authors discussed a possible participation of the disturbance of cellular immunity secondary to the virus infection in the development of the disease.


Comparative effects of centrophenoxine on the picrotoxin convulsive-seizure threshold in non-irradiated and irradiated mice.

A comparative study is made of the effect of centrophenoxine (CP) on the picrotoxin convulsive-seizure threshold (PCST) in non-irradiated and irradiated 3 and 7 days previously male mice. It is found that the CP appliked intracerebroventricularly in doses of 200 and 400 micrograms/mouse (weight 18-22 g), increases PCST. In non-irradiated mice the PCST-increasing effect of CP occurs rapidly (5 min) and it is brief (it can be observed until the 15th min). When the irradiation is performed three days previously, the PCST-increasing effect of CP is prolonged (it is observed until the 6th hour after its application). When the irradiation is performed seven days previously the characteristic features of the PCST-increasing effect of CP are similar to those in the early stage (3 days), the only difference being that the duration of the effect is prolonged to 120 min. Generally, these specificities of the CP effect are valid for all three phases of the convulsive seizure (general excitation, clonic convulsive seizure and tonic convulsive seizure.


[Development of psychiatric care in semi-urban and rural areas of Costa Rica].

Information is given concerning the historical background of Psychiatric Services in Costa Rica. These services have been rendered since the year 1890 when a European style Asylum was opened in San José, the Capital City. The first residency program in Psichiatry begun in the early sixties with its projection into Community Psychiatry during the third year of training as well as the first actions trying to demonstrate to the administrators the usefullness and extension of Mental Health programmes for the future of the country. The residency training program evolved into a national program offering psychiatric assistance throughout the country. Seven out-patient facilities in the metropolitan area plus eleven out-patient facilities in semi-urban and rural areas were founded. To motivate the newly graduated psychiatrists to accept their designation in smaller towns and villages for a full time work was possible because of the experience that they had in Community Psychiatry during their training, there was a clear understanding when signing for the residency programme that at least for two years, they would work in the provinces. A closed relationship after their training with the National Psychiatric Hospital and the Coordination of National Psychiatric Services was kept. In the local, semi-rural communities, the Psychiatrists can hospitalize their train-in local general Hospitals and work closely with the rest of the medical staff.


Bone maturation in children with chronic renal failure. Effect of 1 alpha-hydroxy vitamin D3 and renal transplantation.

In 8 of 11 children with terminal chronic renal failure, bone age was retarded 6 months to 3 years. During hemodialysis the bone maturation rate decreased. 1 alpha-OH vitamin D3 treatment and renal transplantation normalized the bone maturation rate.


Syncope caused by lithium treatment. Report on two cases and a prospective investigation of the prevalence of lithium-induced sinus node dysfunction.

Lithium salts have been widely used for several years in the treatment of manic-depressive psychosis. Various side-effects of lithium salts have been described. The present case report present two patients in whom sinus node dysfunction leading to syncope was caused by lithium. One of the cases showed signs of depressed sinus node function even when not on lithium, but no symptoms arose until lithium treatment was commenced. The second case showed no signs of depressed sinus node function when lithium was withdrawn. To study the prevalence of sinus node dysfunction in patients on lithium therapy, 97 consecutive patients on lithium were examined. The examination included case history, ECG and carotid massage. In two patients lithium could not be ruled out as being responsible for sinus node depression and in one patient the same was true for the atrioventricular node. None of these patients had any symptoms. It is concluded that lithium treatment may result in sinus node dysfunction. This side-effect is, however, not common. Lithium treatment can obviously be instituted in all patients without a history suggesting sinus node dysfunction. Patients with a history of dizziness and/or syncope should not be given lithium until thorough cardiological examination has been carried out. Likewise, a cardiological examination should be performed if patients on lithium develop symptoms of this type.


Propranolol in angina pectoris: duration of improved exercise tolerance and circulatory effects after acute oral administration.

The duration of the effects of single oral doses of 80 and 160 mg of propranolol was studied in 11 patients with stable, exercise-induced angina pectoris. After administration of both doses, plasma propranolol levels peaked at 2 hours in 8 of the 11 patients and thereafter declined exponentially with an average plasma half-life of 3.98 hours (range 1.4 to 4.3) after the 80 mg dose and 4.28 hours (range 1.9 to 5.4) after the 160 mg dose. There was wide interindividual variation in plasma propranolol concentration at any given time after each dose. Treadmill walking time to the onset of angina, the total duration of exercise and the total external work performed were significantly greater by 1 hour after each dose of propranolol than after placebo. This improvement in exercise tolerance persisted unchanged for 8 hours (P less than 0.001) and was still significant although less marked at 12 hours (P less than 0.05). Improvement in exercise tolerance after propranolol was associated with a significant reduction in S-T segment depression during exercise. Both at rest and during exercise, heart rate, systolic blood pressure and rate-pressure product decreased after propranolol, and these circulatory effects persisted for 12 hours. Changes in walking time, heart rate and systolic blood pressure were similar after 80 and 160 mg of propranolol. Despite the increase in exercise duration and in total work performed after propranolol, the rate-pressure product at the onset of angina was lower after propranolol. In view of the prolonged effects of single oral doses of 80 and 160 mg of propranolol, it is suggested that administration of propranolol twice daily should be adequate in treating patients with stable angina pectoris. These studies also demonstrate that routine measurement of plasma propranolol levels is of little practical value in the management of patients with angina pectoris.


Indications for surgical replacement of the mitral valve. With particular reference to common and uncommon causes of mitral regurgitation.

Mitral valve replacement is considered when there is severe mitral stenosis, severe mitral insufficiency or a combination of the two. Ordinarily, surgical replacement is considered only for patients who are in functional classes III or IV and do not respond to medical management. Patients with symptomatic mitral stenosis should be treated with mitral commissurotomy whenever possible. Patients selected for commissurotomy should have a pliable valve, no other major valve dysfunction, sinus rhythm, no systemic embolism and good left ventricular function. Early operation is not ordinarily required. Mitral insufficiency may require mitral valve replacement in six rather common settings: rheumatic disease, rupture of mitral chordae tendineae, postinfarction rupture of a papillary muscle, intractable infective endocarditis, floppy mitral valve and malfunction of a prosthetic valve. Rupture of mitral chordae tendineae can usually be recognized from the history, physical examination, echocardiogram and angiocardiogram. Severe left ventricular papillary muscle dysfunction is usually due to cardiac infarction, and occurs within the first 9 days of infarction. When only a papillary muscle tip is ruptured the patient may survive long enough for a mitral valve replacement. In infective endocarditis, operation is more often needed because of congestive heart failure than because of refractory infection. Evidence of mitral stenosis or insufficiency in a patient with a previously implanted prosthetic valve usually indicates an urgent need for study and early operation. Uncommon causes of mitral incompetence that may require valve replacement are endocardial fibroelastosis, Marfan's syndrome, calcified mitral anulus, osteogenesis imperfecta, methysergide-induced heart disease and carcinoid heart disease.


Small vessel disease of the heart resulting in myocardial necrosis and death despite angiographically normal coronary arteries.

A 46 year old man who had undergone cardiac transplantation 1 year previously had progressive congestive heart failure without evidence of cardiac rejection. Cardiac catheterization and angiography revealed a reduced ejection fraction and cardiac output caused by diffuse left ventricular hypokinesia, but the epicardial coronary arteries were widely patent. The transit time of injected contrast material across the coronary arterial tree was greatly slowed. Within a few days cardiogenic shock and death occurred. The large epicardial coronary vessels were grossly patent at autopsy, although nonstenosing arteriosclerotic plaques were identifiable histologically. However, intramyocardial vessels showed severe arteriosclerotic narrowing, resulting in multiple, diffuse microinfarcts.


Some effects of deoxycholate administration on the metabolism of cholesterol in man.

Hypercholesterolemic subjects in a metabolic ward were kept under uniform dietary conditions until constant levels of serum cholesterol were observed. Oral dosage with deoxycholate (1.5 to 3 g daily for a period of 4 to 10 weeks) resulted in a marked reduction of serum cholesterol concentration. Studies with 14C-labeled cholesterol demonstrated that deoxycholate administration decreased absorption of cholesterol from the human intestinal tract. In these subjects, the turnover rate of serum cholesterol was more rapid during therapy with deoxycholate than during control periods. Deoxycholate appeared to influence the intestinal flora as assessed indirectly by analysis of the types of neutral sterols eliminated with the feces. Decreased synthesis of cholesterol during deoxycholate administration uas demonstrated in a study with 14C-mevalonate. It is concluded that deoxycholic acid can have an important role in the regulation of cholesterol metabolism in humans.


An improved histochemical method for detection of estrogen receptors in mammary cancer. Comparison with biochemical assay.

Unselected, consecutive surgical specimens from 120 women with cancer of the breast were subjected to histochemical assay for the presence of estrogen receptor. A fluoresceinated bovine serum albumin--estradiol conjugate was used that linked estradiol at position 17 and contained 5 mol fluorescein and 4 mol estradiol per mole albumin. Simultaneous competitive binding studies with excess unlabeled estradiol, diethylstilbestrol, and the antiestrogen nitromifene citrate were regularly performed. Results were compared to those obtained by the dextran-coated charcoal receptor assay. Three specimens were necrotic, two others thawed, and two lacked sufficient protein for biochemical analysis. One specimen did not contain tumor, and 11 others showed a predominant nuclear staining pattern. Nuclear receptor was not assayed biochemically. Comparison of results in the remaining 101 cases showed agreement in 92%. The precedure is uncomplicated, economical, and could be performed and interpreted in any pathology laboratory.


Erroneous thyroid-stimulating hormone radioimmunoassay results due to interfering antibovine thyroid-stimulating hormone antibodies.

Apparent elevation of serum thyroid-stimulating hormone (TSH) levels was found in a case of a patient receiving adequate replacement therapy after thyroidectomy for a follicular carcinoma. This was an artifact due to interference with the radioimmunoassay by circulating antibovine TSH antibodies. The double-antibody technic showed spuriously elevated levels, and the single-antibody technic showed low levels of serum TSH by radioimmunoassay in the presence of antibodies.


Incidental medullary thyroid carcinoma in sporadic hyperparathyroidism. An expansion of the concept of C-cell hyperplasia.

Two patients with sporadic primary hyperparathyroidism were found to harbor tiny medullary thyroid carcinomas. In addition, parafollicular-cell hyperplasia was recognized in one of these thyroids by the use of immunoperoxidase stain to localize calcitonin. The possible relationships between these lesions are discussed.


The histopathology of enteric infection with Yersinia pseudotuberculosis.

The gross and microscopic pathologic changes in 70 cases of serologically proven enteric infections with Yersinia pseudotuberculosis are presented. The highest incidence was in young males, and the commonest infecting organism belonged to serologic O-group I. Clinically, the illness resembled acute appendicitis, but the most consistent finding at laparotomy was mesentric lymphadenitis. Surgical specimens examined included 69 mesenteric lymph nodes, 18 appendices, five terminal ileums, and two ascending colons. Histologically, four stages of the disease were identified, leading to the formation of characteristic granulomas with central necrosis and microabscess formation. Ulceration of the intestinal and appendicular mucosa may occur. The illness usually runs a benign course, and antibiotic treatment is rarely necessary. The pathogenesis and differential diagnosis are discussed with reference to the current literature.