Studies of lymphocytes in rheumatoid arthritis. I. Uptake of 125I-heat aggregated human IgG by Fc-receptor bearing lymphocytes. The uptake of 125I-heat aggregated human IgG (125I-HAGG) by monocyte-free peripheral blood lymphocytes was investigated in patients with active rheumatoid arthritis (RA), inactive RA patients with other inflammatory joint diseases (ankylosing spondylitis and Still's disease), and in normal controls. The lymphocytes of patients with RA, whether active or inactive, showed significantly raised levels of 125I-HAGG uptake when compared with normals. Patients with other inflammatory joint diseases showed normal levels of HAGG uptake. High uptake was not due to the presence of cytophilic antibodies and was not related to drug treatment, rheumatoid factor status, patient age, duration of disease, and did not correlate with disease activity. These results indicate that Fc-receptor bearing lymphocytes in patients with RA differ from those of normal subjects and patients with other inflammatory joint diseases. This difference was not due to differences in numbers of Fc-receptor bearing lymphocytes but may be due either to increased numbers of Fc-receptors on each cell or to increased avidity of such receptors for HAGG.


Studies on cold insoluble globulin. I Concentrations in citrated plasma in rheumatic disorders. Cold insoluble globulin (CIG) is a normal glycoprotein of human serum and plasma. The physiological significance of this protein is unknown, but is shows a temperature-dependent relation to fibrinogen and fibrin. It is possible that it represents a substrate for activated fibrin-stabilising factor in the polymerisation of fibrin. CIG is found on the surface of fibroblasts. In the present study CIG was estimated in citrated plasma in 115 patients with rheumatic diseases. Increased amounts were found in patients with systemic lupus erythematosus, secondary amyloidosis in classical and definite rheumatoid arthritis, and in male patients with juvenile rheumatoid arthritis.


Brain scan diagnosis of central nervous system involvement in systemic lupus erythematosus. Twenty-five patients with 29 episodes of active systemic lupus erythematosus with central nervous system involvement were studied according to a uniform protocol. Brain scans were found to be abnormal in all patients studied, and electroencephalograms were abnormal in 20/25 patients. Serial brain scanning was found to be useful in the diagnosis of exacerbations and the monitoring of corticosteroid dosage.


Nitroblue tetrazolium test in psoriatic arthritis, rheumatoid arthritis, and osteoarthrosis. Nitroblue tetrazolium test scores were obtained in 43 patients with psoriatic arthritis, 32 patients with rheumatoid arthritis, and 16 patients with osteoarthrosis. The mean score in all groups was similar and was higher than previously reported in patients awaiting heart surgery or with noninfective dermatoses. The test is not thought to be helpful in differentiating psoriatic arthritis from rheumatoid arthritis, and its usefulness in the diagnosis of septic arthritis superimposed on other forms of arthropathy is limited.


Neutropenia during treatment of rheumatoid arthritis with levamisole. Of 60 patients with rheumatoid arthritis treated with levamisole 35% showed a persistent decrease in neutrophil counts from pre-treatment levels and 6 (10%) develped severe neutropenia of less than 1.0 X 10(9)/1. One of these neutropenic patients recoverd without stopping therapy and the other 5 patients recovered rapidly when the drug was withdrawn. In some patients neutropenia recurred on reinstitution of levamisole.


Metal sensitivity in patients with a hinge arthroplasty of the knee. Fifty patients who had received a hinge arthroplasty of the knee were investigated for possible metal sensitivity. Patients were patch tested against all the metal constituents of the prosthesis. Positive patch tests were found in 32% of patients. Seventeen patients had either lossening or a persistent sterile discharge from the knee. No correlation was found between these complications and metal sensitivity. It was concluded that metal sensitivity is probably not a primary factor in the pathogenesis of complications, particularly loosening.


Observer variation in examination of knee joints. The knees of 20 patients with rheumatoid arthritis were each examined on two occasions on the same morning by three observers. Assessments were made of joint warmth, synovial thickening, effusion, instability, quadriceps power, bony enlargement, range of movement, and knee circumference, and were graded on a scale of 0-4. Analysis of the results shows close intraobserver agreement for all measurements but considerable interobserver variation for all subjective measurements.


Studies with pain rating scales.

Studies with pain rating scales. Good correlation has been shown between pain scores derived from 4 different rating scales. The correlation was maintained when presentation of the scales was separated by a series of questions and by physical examination. There is good evidence that the 4 scales are measuring the same underlying pain variable as they calibrate well. There is also evidence that an 11-point (0-10) numerical rating scale performs better than both a 4-point simple descriptive scale or a continuous (visual analogue) scale.


Provocative agents and the diagnosis of medullary carcinoma of the thyroid gland. Twenty-six patients with known or suspected medullary thyroid carcinoma (MTC) and 21 normal control subjects were tested intravenously on four separate days with calcium gluconate (CG), 2 mg Ca(++)/kg/1 min.; pentagastrin (P), 0.5 ug/kg/ 5 sec.; calcium chloride (CC), 3 mg Ca(++)/kg/10 min.; and a combination of calcium gluconate and pentagastrin (CG + P). Calcitonin (CT) levels were determined by radioimmunoassay on plasma collected before and immediately following each test infusion. In none of the 21 control subjects was there a clear increase in CT above 200 pg/ml following any of the four provocative tests. Conversely, in all 26 patients with known or suspected MTC, plasma CT levels were markedly increased (>300 pg/ml) following the combined infusion of CG + P. The peak CT response was greater with CG + P than with a) CG alone (22 of 24 patients, p < 0.002), b) P alone (25 of 26 patients, p < 0.002), or c) CC alone (17 of 17 patients, p < 0.002). Of 12 MTC patients with undetectable basal calcitonin levels, all had peak responses greater than 300 pg/ml following CG + P, whereas such responses occurred less often following CG alone (8 of 12) or P alone (8 of 12). The results demonstrate that the combined administration of pentagastrin and calcium gluconate constitutes a more effective and reliable stimulus for CT secretion from MTC cells than the use of either agent alone, and appears the most useful single screening test for the detection of occult MTC.


Prevention of liver reticuloendothelial systemic host defense failure after surgery by intravenous opsonic glycoprotein therapy. Depression of the reticuloendothelial system (RES) was observed in rats following operative trauma consisting of laparotomy and jejunal enterotomy. This RES depression was manifested as a significant impairment in the phagocytic clearance of intravenously injected blood-borne test colloid mediated by a decline in hepatic Kupffer cell phagocytosis. Reticuloendothelial systemic host defense depression was correlated with a significant decline in bioassayable and immunoreactive opsonic alpha(2)SB glycoprotein concentration over a 1-3 hr postoperative period with rebound elevation in opsonic activity by 24 hr postsurgery. Intravenous administration of purified opsonic alpha(2)SB glycoprotein at the end of the operation prevented postoperative opsonic deficiency and restored normal hepatic RES phagocytic function. These studies coupled with previous observations in patients following surgery or after severe multiple trauma suggest that reticuloendothelial depression during and after operation mediated by opsonic deficiency may lead to a precarious imbalance between systemic host defense and the dissemination of blood-borne foreign and effete particulate matter such as injured platelets, fibrin microaggregates and immune complexes. Immunoreactive serum opsonic alpha(2)SB glycoprotein determinations may serve as a valuable index of hepatic RE clearance capacity and opsonin therapy may potentially be a selective means to augment systemic host defense.


Improved limb salvage after arterial embolectomy. Between January 1965 and August 1977, 122 patients with 135 arterial emboli were treated on the Peripheral Vascular Service at the Ohio State University Hospital. The heart was the source of the embolus in 94 patients (77%), one-third of whom had experienced a myocardial infarct. Thirteen patients died after the operation, which in 102 patients (84%) consisted of embolectomy only, making the hospital mortality 10.6%. Fourteen patients (11.5%) required subsequent amputations during the same hospitalization or on a later admission. The corrected limb salvage rate of 80.9% was unrelated to the length of delay in presentation. Although only 70 patients (57.4%) had palpable distal pulses following operation, 89 (73%) had a functional limb at the time of discharge or on later follow-up. An aggressive approach to the patient with an arterial embolus, regardless of the duration of symptoms, is urged. Embolectomy under local anesthesia is advocated in all cases after prompt correction of fluid and electrolyte imbalance and stabilization of the underlying cardiac disorder, except in patients with frank gangrene and irreversible rigor. In the absence of distal pulses or obvious revascularization, an intraoperative arteriogram is mandatory.


Human umbilical veins and autogenous veins as canine arterial bypass grafts. Glutaraldehyde treated human umbilical veins (Dardik Biograft) were used to bypass short segments of the femoral artery in 15 dogs and were compared to autogenous jugular veins placed in the contralateral femoral artery of each animal. All 15 autogenous jugular veins remained patent for the four month period of observation whereas thrombosis occurred in seven of 15 umbilical vein grafts. This patency rate of 53% was significantly lower than that observed for autogenous jugular veins (p less than 0.01). Neointimal Fibrous Hyperplasia (NFH) a the proximal anastomosis was responsible for six of the seven umbilical vein graft occlusions. Of the eight patent umbilical veins, five had varying degrees of proximal anastomotic stenosis secondary to NFH. Histological examination of each graft revealed significant fibroblastic proliferation and collagen deposition within the lumen of stenosed and thrombosed grafts. Although human umbilical veins have distinct advantages over other prosthetics, such as availability and flexibility, the incidence of experimental neointimal fibrous hyperplasia causing anastomotic stenosis and thrombosis is prohibitively high.


Results of 100 consecutive femoropopliteal vein grafts for limb salvage. One hundred consecutive patients with femoropopliteal autogenous vein grafts for limb salvage were reviewed five years later. In this group 40% died and 30% of the limbs had been lost at the end of five years. Limb survival correlated best with adequacy of distal run-off, but not with the presence or absence of diabetes. Forty-seven per cent of the grafts were still patent among surviving patients, and when combined with the limbs that were viable despite failure of the original graft, 70% of the limbs were salvaged among the survivors at five years. Temporary graft patency was effective in preserving ischemic tissue by facilitating healing of ulcers or limited amputations. Femoral-popliteal bypass grafting in the presence of advanced ischemia is capable of improving the quality of life for many of these patients.


Leg ischemia following surgery for abdominal aortic aneurysm. Resection of an abdominal aortic aneurysm was associated with intraoperative or postoperative leg ischemia in seven of 100 consecutive survivors of this procedure. Distal embolization of thrombus and debris is the apparent cause in the majority of cases (six). One case of stenosis at a graft-to-vessel anastomosis was identified. Early (intraoperative) thromboembolectomy averted tissue loss in four cases. The role of concurrent lumbar sympathectomy in ameliorating ischemic tissue loss is evaluated. Postaneurysmectomy leg ischemia may accompany other serious complications, particularly hypotension and renal failure.


Thymomas in patients with myasthenia gravis. The records of 141 patients with myasthenia gravis who had thymomas were reviewed. In this series there were 69 noninvasive tumors and 52 invasive tumors. The five year survival for all patients was 60%, with the invasive group demonstrating a poorer prognosis than the noninvasive. The remission rates for the whole group (both invasive and noninvasive) of myasthenics was quite low (7%). Although the overall survival of this series of patients was relatively high, it is felt that by earlier diagnosis and a more aggressive surgical approach their prognosis will be even better.


Decreases in histamine forming enzyme activity of non-metastasizing fibrosarcomas in hamsters with progressive tumor growth. A marked and progressive decrease in the activity of the histamine forming enzyme, histidine decarboxylase (HDC), of tumors was found to be associated with the progressive growth of SV-40 virus induced and transplanted syngeneic non-metastasizing fibrosarcomas in inbred LSH Syrian hamsters. Histamine forming enzyme activity was highest in the smallest tumors (p < .005) and in the tumors with the slowest growth rate (p < .005, r - 0.84). Tumor histamine forming enzyme activity was highest for each interval of animal exposure to inoculated tumor cells in those animals which had limited their tumor growth to the smallest tumor size. These findings suggested a local anti-inflammatory effect of progressive tumor growth. Induced local inflammation by repeated intratumor injections of bradykinin markedly elevated tumor histamine forming enzyme activity above expected levels for tumors of the same size in a small group of individual animals which were sampled at random from a larger group of animals which were being studied for the tumor growth kinetics effects of repeated intralesional injections of bradykinin. Tumor histamine forming enzyme activity was highest in those animals which were managed by the frequency of injection and dose schedules which were found in the tumor growth kinetics study to be most effective in limiting tumor growth. These findings suggested that the observed anti-inflammatory effects of progressive tumor growth may be reversed by locally induced inflammation at the tumor site with beneficial effects on tumor growth.


Some properties shared by amino acids and entero-oxyntin. The intestinal phase of gastric secretion has been thought to be due to the release of a hormone from the gut mucosa, and several properties have been attributed to this as-yet unidentified hormone. An amino acid solution, known to stimulate gastric secretion, was tested to see if it possesses several of these properties, i.e., inactivation by the liver, and the ability to augment the maximum responses to pentagastrin and histamine. In six dogs with Heidenhain pouches the gastric secretory responses to peripheral and portal intravenous administration of a solution of mixed L-amino acids were measured. The mean peak response of three such separate peripheral infusions in each dog was 370 microEq/30 minutes while the peak response to intraportal infusion was only 45 microEq/30 minutes (p < .05). In three dogs with Heidenhain pouches the intravenous administration of amino acids together with pentagastrin resulted in significant augmentation of the peak response to pentagastrin alone (p < .025). Similarly, administration of amino acids with histamine resulted in augmentation of the peak response to histamine alone (p < .05). Because amino acids mimic the actions of the "intestinal phase hormone" in these respects it is suggested that they may account, at least in part, for the intestinal phase of gastric secretion. In addition, amino acids absorbed during protein digestion may contribute to the gastric hypersecretion which is regularly seen with portosystemic shunts.


Influence of histocompatibility and transplant site on survival. Suggestions that endocrine tissue is privileged, in that it may not be as severely damaged by the allograft reaction, provided the stimulus for an evaluation of thyroid transplantation across various histocompatibility barriers and into a number of different recipient sites. Results of allografting reveal that Ag-B compatibility allows for prolonged survival of thyroid tissue (much longer than skin in the same histocompatibility combinations) in the following sites: intramuscular, intradermal, renal subcapsular, and anterior chamber. Only the intrasplenic site, however, did not allow survival of even weakly incompatible grafts. In addition, all recipients of thyroid allografts rejected subsequent donor strain skin grafts in an accelerated manner, attesting to the normal antigenicity of thyroid. This finding, that thyroid is a "relatively privileged" tissue, has not been reported previously and is encouraging, since it suggests the potential success of clinical transplantation of other endocrine tissue less easily replaced than thyroid by administration of naturally occurring of synthetic analogues. Further, mild immunosuppression may serve to prolong survivals of allografts of endocrine tissue such as parathyroid or pancreatic islets, especially if an immunologically privileged site is employed.


Susceptibility of the pancreas to ischemic injury in shock. The pancreas, like the kidney, is highly vulnerable to ischemic necrosis. This form of pancreatic injury may express itself as prolonged hyperamylasemia with only minimal signs or symptoms of inflammation, or may produce severe pancreatitis followed by abscesses and death. Autopsy examination of patients dying after oligemic shock showed a 9% incidence of major pancreatic injury if there was not concomitant acute renal tubular necrosis (ATN), but a 50% incidence in those with ATN. Similarly, among patients dying after non-oligemic shock, 12% of those without ATN had major pancreatic injury but 35% with ATN also had pancreatic ischemic injury. Among 13 selected patients examined prospectively after being in shock, pancreatic injury was indicated by hyperamylasemia, hyperlipasemia, elevated amylase/creatinine clearance ratio, and elevated circulating isoamylases specifically of pancreatic origin. Four of the 13 had clinical manifestations of pancreatitis. Not only must shock be added to this list of causes of pancreatitis, but pancreatic ischemia due to hypoperfusion may also be the critical factor which causes the progression from edema to necrosis in other forms of pancreatitis, including those associated with alcohol and biliary disease.


Antibiotic concentration in human wound fluid after intravenous administration. Since the wound is the most common focus of infection in the surgical patient, adequate levels of antibiotic within the wound ar essential. This study examines the concentrations of antibiotic achieved in human wounds. Fluid was collected at timed intervals on the first postoperative day from the wounds of 56 patients receiving antibiotics after regional lymph node dissection. Antibiotic concentration was determined by bioassay. Six antibiotics were studied: cephalothin, cefazolin, cephapirin, oxacillin, ampicillin and clindamycin. The cephalosporins and penicillins showed similar patterns of appearance in the wound fluid. The peak level occurred early (1--1 1/2 hours) with subsequent slow decrease. Clindamycin produced nearly constant levels in wound fluid. The concentration of each antibiotic in wound fluid surpassed the serum levels after 2.5 hours. At the dosages studied each antibiotic produced wound fluid concentrations greater than the MIC for most susceptible organisms. Higher doses provided higher wound fluid levels. The rate of appearance and the levels achieved should be considered in the choice of antibiotics in the surgical subject.


Delayed presentation of traumatic diaphragmatic hernia. Twenty-five patients with traumatic diaphragmatic hernia discovered at least five months after injury are described, of whom 18 were male and seven female. All but one hernia occurred on the left side. Stab wounds were the etiological factor in 22 patients and blunt trauma in three. The diagnosis was most often made by a chest or abdominal radiograph, but barium ingestion confirmed the diagnosis in ten patients. Intercostal drainage of gastric contents provided the diagnosis in two patients. In all nine patients initially approached by a thoracotomy or a thoracoabdominal incision, the hernia was easily reduced and the defect repaired. Although reduction and repair were easily accomplished by the abdominal route in seven patients, this approach was unsatisfactory or inadequate in six others. The colon and stomach were usually in the chest, and strangulation occurred in five patients. The mortality was 20% but rose to 80% when gangrene was present.


Association of sepsis with an immunosuppressive polypeptide in the serum of burn patients. One hundred ninety serum samples from 51 burned patients were tested for immunosuppressive activity which might explain decreased host immune competence following thermal injury. The serum from a variable but significant percentage of these patients suppressed the response of normal human peripheral blood lymphocytes to phytohemagglutinin. The occurrence of immunosuppressive activity paralleled the severity of the injury. Ten of ten severely burned patients (severity index greater than 40), but only 20 of 30 patients with index 10--39.9, and three of 11 patients with Index 0--9.9 developed suppressive serum. Differences between these groups were significant (p less than .05). In all 19 patients who became septic, immunosuppressive serum activity immediately preceded or coincided with the septic episode. In contrast to the effect on lymphocytes, burn sera stimulated fibroblast proliferation. Immunosuppressive activity did not correlate with serum cortisol levels, blood transfusion, protein-calorie malnutrition, or anesthesia. Suppressive sera were not cytotoxic. A majority of the active serum factor(s) was contained in a low molecular weight (less than 10,000 daltons) polypeptide subfraction.


Unusual aspects of atrial myxoma.

Unusual aspects of atrial myxoma. Cardiac myxomas are infrequently encountered lesions. Certain aspects of these tumors are unusual and include right atrial location, calcification, valve destruction, hematologic abnormalities, occurrence in children, and familial occurrence. A 12-year-old girl manifesting all of these unusual aspects of myxoma is described and each of the unusual aspects is discussed.


Endorectal mucosal resection without proctectomy as an adjunct to abdominoperineal resection for nonmalignant conditions: clinical experience with five patients. Five patients with chronic ulcerative colitis underwent endorectal excision of the rectal mucosa without removing the rectal muscle in combination with total colectomy and cutaneous ileostomy. This operative technique will cure the patient of the primary disease and obviates many of the usual unpleasant complications following total proctectomy, such as prolonged perineal drainage and sexual and bladder dysfunction. It has the further advantages of lower operative blood loss and earlier safe ambulation. On the basis of favorable clinical experience with these patients, we believe that the operation warrants further clinical trial in patients who have biopsy-proven ulcerative colitis without severe rectal ulcerations as well as in certain other nonmalignant conditions originating in the rectal mucosa.


Veterans Administration Cooperative Study on Bowel Preparation for Elective Colorectal Operations: impact of oral antibiotic regimen on colonic flora, wound irrigation cultures and bacteriology of septic complications. A ten hospital cooperative study comparing prophylactic oral neomycin and erythromycin base versus placebo demonstrated clinical efficacy of the antibiotics in preventing septic complications following elective colon operations. The present report concerns microbiological studies accomplished during this trial. Cultures of colon contents during surgery showed the antibiotic prep reduced concentrations of both aerobes and anaerobes by approximately 10(5) bacteria/ml. Virtually all major bacterial components of the normal flora were affected. Wound irrigation specimens at the time of closure failed to predict subsequent wound infection, but significantly fewer antibiotic recipients had positive irrigation cultures. Postoperative stool specimens showed that the oral antibiotics did not cause an emergence in resistant forms. Bacteriological studies of postoperative infections indicated that most postoperative infections involved a mixed aerobic-anaerobic flora, and that Bacteroides fragilis accounted for six of eight episodes of bacteremia.


Antibiotic prophylaxis in vascular surgery. Preoperative and intraoperative antibiotic prophylaxis of infection in peripheral vascular surgery has been widely used although controlled studies have been lacking. A randomized, a prospective, double-blind study of cefazolin versus placebo during 565 arterial reconstructive operations was performed at this hospital from February 1976 through August 1977. Among the 462 patients undergoing surgery of the abdominal aorta and lower extremity vasculature, there was a highly significant difference in the infection rates: 6.8% for placebo recipients versus 0.9% for cefazolin recipients (p less than .001). Of the 18 infections, four involved vascular grafts and all four graft infections occurred in the placebo group. Over 8% of abdominal wounds of patients receiving placebo became infected versus 1.2% of cefazolin patients (p less than .05). Groin wounds were infected infrequently, 1.1% for placebo patients versus none for cefazolin patients. No infections occurred among 103 brachiocephalic procedures. Skin antisepsis was analyzed retrospectively. Infection rates were significantly higher (p less than .01) following hexachlorophene-ethanol versus a povidone-iodine skin preparation. Adverse effects of cefazolin were carefully monitored: no rash, phlebitis, or emergence of resistant strains was observed. A breif perioperative course of cefazolin and povidone-iodine skin antisepsis are recommended in vascular reconstructive surgery of the abdominal aorta and lower extremity vasculature.


Surgical management of Cushing's syndrome with emphasis on adrenal autotransplantation. Cushing's syndrome may be caused by pituitary ACTH, ectopically produced ACTH, adrenocortical tumor or medication. Cushing's disease, due to excessive pituitary ACTH resulting in adrenocortical hyperplasia, remains a complex endocrine disorder for which no single treatment is wholly satisfactory. Twenty-two patients with surgically treated Cushing's syndrome are presented: Four with benign adrenocortical adenoma, two with adrenocortical carcinoma and 16 with adrenocortical hyperplasia. The four benign adenomas were excised with the one death due to respiratory failure and sepsis. Both patients with carcinoma and liver metastases died of their tumors. Of the 16 patients with adrenocortical hyperplasia and Cushing's disease, eight underwent subtotal adrenalectomy and thereafter eight had total intra-abdominal adrenalectomy with autotransplantation of adrenal tissue to the thigh. There was one operative death. Total adrenalectomy has now replaced subtotal resection in most clinics. All eight of the patients who had adrenal autotransplantation exhibited biopsy or functional evidence of some degree of graft survival. On patient stopped steroid replacement permanently and another developed recurrent Cushing's syndrome from the grafts. Of a total of 26 reported patients with adrenal autotransplants surveyed, 22 exhibited evidence of graft survival, 16 were able to discontinue steroid replacement therapy and three eventually developed recurrent Cushing's syndrome from the transplants. There is now strong evidence that most patients with Cushing's disease harbor a pituitary basophil ademona, and in the future the initial surgical attack may be directed to the pituitary rather than to the adrenals.


Asymptomatic carotid bruit: long term outcome of patients having endarterectomy compared with unoperated controls. During 20 years (1957-1977), 1286 carotid endarterectomies were performed on 1022 private patients with cerebrovascular insufficiency. Included were 132 patients undergoing 167 endarterectomies for asymptomatic cervical carotid bruits. Ages ranged from 42 to 82 years (mean: 64.7). Operative mortality was zero. There were two transient and two permanent operation-related neurologic deficits. Complete follow-up was achieved, extending to 184 months. During postoperative follow-up, six patients (4.5%) developed TIA's appropriate to the unoperated artery, three patients had strokes (2.3%), and three patients died of strokes (2.3%). To characterize the natural history of asymptomatic bruit and determine proper indications for prophylactic endarterectomy, a control series of 138 additional patients with asymptomatic bruit not operated upon when the bruit was discovered was studied. Ages ranged from 39 to 86 years (mean: 65.7). During follow-up extending to 180 months, 77 patients (55.8%) remained neurologically asymptomatic, 37 patients (26.8%) developed TIA's one month to 99 months after detection of bruit, and 24 patients (17.4%) sustained mild to profound frank strokes one week to 124 months postdetection. Three of these 24 (2.2%) died of stroke. Asymptomatic carotid bruits may be potential stroke hazards, the risk of which can be significantly reduced by appropriately applied endarterectomy. A protocol for managment is presented.


Total pancreatectomy of end-stage chronic pancreatitis. The metabolic consequences and the clinical results of total pancreatectomy for end-stage chronic pancreatitis are detailed. This experience, accumulated between the years 1952 and 1976, adds 26 cases to the world's literature, which now contains 53 cases reported singly or in small series. The patients were selected on the basis of far-advanced, incapacitating disease in three patients and the failure of 62 previous related operations in 23 patients. Total pancreatectomy was performed with a zero hospital mortality but with serious inhospital morbidity. After discharge, 24 patients required 55 hospital readmissions and 18 related surgical operations; 12 patients have died, five of unrelated causes. Of 14 living patients, five consider themselves to be in good to excellent condition, six in fair condition, and three in poor condition. Twelve thought they were improved over their preoperative state. Our estimate of the result in living patients was similar. In those 12 who died, only four had satisfactory results. The results are also evaluated relative to level of activity, presence of abdominal pain, use of narcotics, weight, alcohol consumption, and the efficiency of endocrine and exocrine replacement. In general, the procedure is effective for relief or amelioration of pain, but the patients' personalities preclude complete adaptation to the apancreatic state rehabilitation. A failure to thrive is the common denominator.


The Elective Surgery Second Opinion Program. The results of the Cornell Elective Surgery Second Opinion Program are presented. From February 1972 to January 1978, 7053 patients were evaluated for proposed elective surgery, and in 27.6% of these, the operations were not approved. The subspecialties of orthopedics and gynecology demonstrated the highest rates of non-confirmation, while that for general surgery was 18%. A group of 318 patients with general surgical diagnosis are reviewed. The percentage of nonconfirmed surgery for this group was 15 percent. The most common reasons for not approving the operations were absence of pathology and failure to utilize medical therapy when indicated.


Correlation of estrophilin content of primary mammary cancer to eventual endocrine treatment. The estrogen receptor protein content of recurrent breast cancer correlates well with the clinical response of hormonal manipulation. This predictive value of the ER of the primary tumor obtained at the time of mastectomy has not yet been proven. If this predictive capability should hold for primary tumors and eventual endocrine treatment, the ramifications are obvious: endocrine therapy could be offered to patients on a rational basis and adjuvant therapy could be considered on a plausible biochemical basis. This report details our observations as to the ER content of the primary tumor and the eventual result of endocrine therapy. Thirty-seven patients whose tumor ER was determined from the primary tumor eventually underwent some form of endocrine therapy for recurrent disease. Fifteen of the primary tumors had significant ER content and 22 possessed insignificant amounts. Only one of the 22 patients with insignificant ER content was benefited by endocrine treatment. Those patients whose tumors contained low amounts of ER experienced recurrence of their disease more rapidly than did those with higher ER content. There was no correlation of age, cell type of tumor or metastatic site with the ER content of the tumor. There is a positive correlation between response to chemotherapy and ER content of tumor. Measurement of the estrogen receptor protein content of the primary breast tumor is a reliable method for choosing patients for eventual endocrine therapy. Those patients whose tumors contain insignificant estrophilin are not candidates for such attempts at palliation.


Medullary thyroid carcinoma: relationship of method of diagnosis to pathologic staging. Medullary thyroid carcinoma (MTC) develops in virtually all patients affected with multiple endocrine neoplasia type II (MEN II), a disease inherited as an autosomal dominant trait. The thyroid tumor cells secrete calcitonin (CT) and the detection of elevated plasma levels (>300 pg/ml) of this hormone in MEN II kindred members strongly suggests the presence of MTC even though it may not be evident clinically. Intravenously administered calcium ion (Ca(++)) and pentagastrin (Pg) are potent CT secretagogues which are of particular value in establishing the early diagnosis of MTC. In evaluating seven kindreds with MEN II, we detected 90 patients with MTC. Depending on the method of diagnosis, they could be divided into three categories: Group 1; patients with no clinical evidence of MTC whose undetectable basal plasma calcitonin levels became elevated following intravenous Ca(++) or Pg, Group II; patients with no clinical evidence of MTC who had elevated basal plasma CT levels, and Group III; patients with clinically evident MTC. At the time of diagnosis of MTC, the patients in Group I were younger (20.5 +/- 1.9 years) than the patients in Group II (32.5 +/- 4.7 years, p < 0.005) and Group III (34.3 +/- 2.0, p < 0.00005). The incidence of residual MTC, as indicated by an elevated plasma CT level following provocative testing postoperatively, was less frequent in patients diagnosed biochemically ([6/34]; Group I, 4/26 and Group II, 2/8) than in those diagnosed clinically (Group III, 15/26, p < 0.002). Furthermore, regional nodes were involved less often in patients diagnosed biochemically ([5/28]; Group I, 2/22 and Group II, 3/6) than in those diagnosed clinically (Group III, 15/24, p < 0.02). Distant metastases were only evident in Group III patients. Patients with MEN II who had the diagnosis of MTC established biochemically rather than clinically, had a more favorable pathological stage of disease at the time of thyroidectomy. This was especially true if the biochemical diagnosis had been by provocative testing.


The Zollinger-Ellison syndrome--23 years later. The effects of recent diagnostic and therapeutic advances were assessed in 65 patients with the Zollinger-Ellison syndrome (ZES). Twenty-seven patients seen between 1955 and 1970 were compared with 38 patients seen between 1971 and 1977. The earlier patients had a higher incidence of virulent ulcer disease (56% vs. 24%), other endocrinopathies (48% vs. 13%), and malignant gastrinoma (44% vs. 25%). Earlier diagnosis is the result of liberal use of serum gastrin measurements and provocative tests for gastrin release (calcium and secretin), and an increased awareness of this syndrome. Because their basal gastrin values were in a range that overlapped ordinary ulcer disease, 47% of patients encountered in recent years required provocative testing with secretin for diagnosis. If the gastrin concentration falls to normal following resection of a gastrinoma, the tumor has probably been completely removed. In our patients, gastrin measurements after total gastrectomy had no prognostic significance in regards to clinical progression or regression of the neoplasm. Of 12 patients treated with cimetidine, nine experienced symptomatic improvement, and three did not. Resection of the gastrinoma should be attempted if the lesion is solitary and located in the body or tail of the pancreas, or if it is an isolated duodenal lesion. Otherwise, total gastrectomy remains the treatment of choice. In 38 patients, total gastrectomy with Roux-en-Y esophagojejunostomy was followed by 97% survival and minimal difficulties with nutrition or dumping.


Progress in treatment of thoracoabdominal and abdominal aortic aneurysms involving celiac, superior mesenteric, and renal arteries. This is a report of surgical treatment of thoracoabdominal aortic aneurysms and aneurysms of the abdominal aorta from which the visceral vessels arise during the 18 year period from April 5, 1960, to April 20, 1978. The extent of aneurysm is divided into five groups. Group I (10 patients) involved most of the thoracic and abdominal aorta down to celiac axis. Group II (22 patients) involved most of the thoracic and abdominal aorta distal to left subclavian artery. Group III (20 patients) were those with lesser involvement of the thoracic aorta and most of the abdominal aorta. Group IV (18 patients) with involvement of the entire abdominal aorta and Group V (12 patients) with involvement of lower abdominal aorta and renal arteries. Treatment in the majority of these cases was by graft inclusion technique with visceral vessel reattachment by direct suture of orifice to openings made in the graft. Intercostal and/or lumbar arteries were also reattached in some with the more extensive lesions. Aortic and renal artery occlusion times varied from 15 to 155 minutes. Paraplegia developed in five patients with the more extensive lesions but was reduced to one-third and made less severe by reattaching intercostal and lumbar arteries. Renal dysfunction was mild in four patients and severe in three patients after operation. All these were transient except one who died while recovering from renal failure. The latter cases were those difficult to reattach or were not initially successful and required reoperation. Of the 82 patients, 77 (94%) survived operation and long-term followup was obtained in 95% of cases, 23 performed over five years ago. Actuarial curves were constructed and compared to survival curves following simple infrarenal abdominal aortic resection. The survival rate both immediately and at six years, were the same.


Protective effect of a novel imidazole derivative against cerebral anoxia. The protective effect of 1-[2-(2-chlorobenzoyl)-4-nitrophenyl]-2-(diethylaminomethyl) imidazole fumarate (Y-9179) against cerebral anoxia was investigated with a variety of experimental models in mice and rats. Y-9179, at doses lower than 1 mg/kg, showed a consistent protective action against the cerebral anoxia in all of the models studied: hypoxia, ischemia, histotoxic and asphyxic anoxia. The antianoxic activity of Y-9179 was found to be about 100 times greater than that of pentobarbital. This anti-anoxic effect was observed at very small doses at which neither sedation nor motor depression was induced. There was no decrease in the protective effect or no adverse effect even at as high a dose as 30 mg/kg, which corresponded to about 150 times the effective dose. The universal anti-anoxic properties of Y-9179 may be useful both clinically and as a pharmacological tool to elucidate the physiological significance of cerebral anoxia.


Pharmacokinetics of deslanatoside C-3H administered parenterally to the guinea-pig, rabbit and dog. The pharmacokinetics of Deslanatoside C-3H, a short-acting polar cardiac glycoside, were investigated in the guinea-pig, rabbit and dog, after parenteral administration. Deslanatoside C was on average 20% plasma protein-bound and had a red blood celle/plasma partition ratio of 1/9. Tissue uptake of Deslanatoside C observed in the guinea-pig seems on average to be higher than in rabbits. Among the various organs and fluids tested, the highest levels were encountered in the urine, bile and kidneys of both the guinea-pig and rabbit. The main excretory route of this glycoside was via the urine, although significant amounts were excreted via the bile in all the three species tested. Cumulative urinary excretion 24 hr after i.v. injection was 50% (75% of which in unchanged form) in the guinea-pig, 46.5% (86% of which in unchanged form) in the rabbit, and 42.9%(84% of which in unchanged form) in the dog. Among the cardiac glycosides, Deslantoside C seems to possess the highest urinary excretion rate, which has in fact also recently been confirmed in human subjects.


Angiotensin II blockade in congestive heart failure. Five of 11 normotensive patients with congestive heart failure responded to an infusion of the specific angiotensin II antagonist, saralasin, by reducing systemic vascular resistance from 2274 +/- 418 to 1690 +/- 351 dynes/sec/cm-5 (mean +/- standard error). This decrease was accompanied by a reduction in left ventricular filling pressure from 19.4 +/- 5.9 to 11.6 +/- 4.0 mm Hg, an increase in cardiac index from 2.2 +/- 0.4 to 2.7 +/- 0.4 l/min/m2 and a decrease in mean arterial pressure from 95 +/- 9.8 to 86 /+- 8.6 mm Hg. In the other 6 patients with congestive heart failure and in 4 controls, saralasin produced either no change or slight increases in systemic vascular resistance. Plasma renin activity did not differentiate responders from non-respnders. Specific inhibition of angiotensin may provide a means for reducing inappropriately high peripheral resistance in some patients with congestive heart failure.


Tension development and associated calcium influx of control and reserpine pretreated rabbit aortae in response to norepinephrine, isoproterenol and acetylcholine. The influence of reserpine (3mg/kg) pretreatment on phasic and tonic components of the contractile responses of rabbit aortae to maximally effective concentrations of norepinephrine, acetylcholine, and isoproterenol and on agonists-induced movements of 45Ca during these responses were studied. Four hours after reserpine administration, there were no histological changes, in extracellular space, and no change in tissue water, sodium, calcium or magnesium. Potassium contents were slightly decreased and the catecholamine content was depleted by 95%. The responses to the three agonists were enhanced in the reserpine pretreated tissues. The absence of calcium eliminated the slow tonic componenet of the responses. Reserpine induced an increase in lanthanum (La3+) resistant 45Ca uptake. The three agonists induced an increase in La3+ resitant 45Ca uptake of equal magnitude in both reserpine pretreated and control tissues. Lanthanum ion affected 45Ca efflux similarly in both reserpine pretreated and untreated tissues. The results suggest that a major portion of the enhanced responsiveness of rabbit aortic strips following reserpien administration is the result of a change in calcium retention in those tissue stores mobilized by these agonists to initiate the fast, phasic componenet, and is, therefore, a reflection of an increased agonist intrinsic activity.


Inhibition of 45Ca movements by lowered temperature or lanthanum in rat brain slices. Different components of 45Ca movements in rat cortex, striatum and hypothalamus slices were delineated by conditions and ions which selectively alter Ca2+ uptake, binding or extrusion. Equilibration of 45Ca was qualitatively similar in all three tissues and was attained within 30--60 min. The 45Ca tissue-medium ratios obtained in 1.5 mM Ca2+ solutions were increased 15--30% in 0.1 mM Ca2+ solutions and doubled in 0-Ca solutions. Efflux of 45Ca from slices can be described in terms of two components. Lowering the temperature to 0 degree C increased 45Ca uptake into the slower washout component and markedly decreased 45Ca efflux. Exposure to 1.5 mM La3+ decreased both 45Ca uptake and efflux. The inhibitory effects of 0 degree C and La3+ on 45Ca efflux were additive. Uptake of 45Ca in slices incubated in 1.5 mM Sr 2+-substituted (0-Ca) solutions was more similar to that in 0-Ca solutions than in 1.5 mM Ca2+ solutions. Thus, Ca2+ distribution is qualitatively similar in slices from different rat brain areas, loss of 45Ca is an energy dependent process which is at least partially coupled to Ca2+ uptake, decreased temperature inhibits Ca2+ extrusion, La3+ impedes uptake and subsequent binding of Ca2+, and Sr2+ does not prevent the major portion of 45Ca uptake at cellular binding sites. Use of 0 degree C and La3+ to inhibit discrete components of Ca2+ fluxes in rat brain area slices provides a basis for investigation of the mechanisms by which other agents can alter Ca2+ distribution in the central nervous system.


Comparative effects of amiodarone, perhexiline and bepridil on the cardiac rhythms of the unanesthetized dog in chronic heart block. The effects of amiodarone, perhexiline and bepridil, which decrease effort cardioacceleration although they have no adrenergic beta blocking properties, were studied in the unanesthetized dog in chronic heart block. All three products decreased atrial rate in a durable way after an initial phase of tachycardia. Amiodarone had no depressant effect on idioventricular rate; however, this was significantly slowed by the other two compounds.


Antihypertensive effects of delta9-tetrahydrocannabinol. Repeated oral administration of delta9-tetrahydrocannabinol (delta9-THC, 25 mg/kg) reduced systolic blood pressure in conscious spontaneously hypertensive rats. Tolerance to the antihypertensive actions of delta9-THC failed to develop during the 10-day treatment period. The failure of delta9-THC to alter blood pressure in normotensive rats suggests that the hypotensive action of delta9-THC is dependent, in part, on baseline blood pressure.


Hyperglycemic, antihypertensive and antidiuretic properties of Go. 8288 and its comparison with diazoxide. Hyperglycemic, antihypertensive and antidiuretic activities of Go.8288 and diazoxide were evaluated in the rat. Go.8288 and diazoxide induced hyperglycemia which was blocked by adrenalectomy and demedullation. Pretreatmnet with hydrocortisone completely restored the hyperglycemic effect of diazoxide but only partially that of Go.8288. The hyperglycemic effect of Go.8288 and diazoxide was antagonized by glibenclamide, whereas tolbutamide antagonized only diazoxide-induced hyperglycemia. Pretreatment with oxprenolol antagonized diazoxide-induced hyperglycemia but not that of Go.8288. Guanethidine antagonized the hyperglycemic effect of Go.8288 but not that of diazoxide. Go.8288 and diazoxide markedly inhibited insulin secretion in vivo. Unlike Go.8288, diazoxide further accentuated the hyperglycemic effect in the streptozotocin diabetic rat. Diazoxide significantly increased plasma FFA and plasma renin activity but Go.8288 had no effect. In the normotensive cats and dogs and renal hypertensive rats both compounds lowered arterial blood pressure. Unlike diazoxide, Go.8288 was active orally in normotensive dogs. Similar to diazoxide Go.8288 showed an antidiuretic effect in the rat. It is therefore concluded that despite some similarities, Go.8288 shows important differences in its biological profile from that of diazoxide.


Placental transfer and tissue distribution of dextro-amphetamine in the mouse. 3H-d-amphetamine (5 mg/kg, free base) was injected i.p. to male and non-pregnant female mice and to pregnant female mice on day 16 of gestation. The tissue levels of amphetamine were  examined as a function of time. Peak concentrations in matured tissues occurred at 15 min, those in placenta, whole fetus, fetal brain and liver at 1 hr. No notable differences were detected in tissue levels of amphetamine in males and non-pregnant females. Disappearance of amphetamine from tissues of pregnant animals was slower than those of other groups. At 15 min, the fetal brain and liver accumulated 1/6 amounts of amphetamine compared to corresponding maternal tissues. Pregnant animals excreted significantly lower amount of total radioactivity compared to non-pregnant females. It is concluded that amphetamine was transported across the placenta and that the lower concentrations in fetal tissues compared to maternal tissues appear to be due to several physico-chemical factors that regulate the transplacental transfer of a foreign chemical compound.


Effects of prazosin and phentolamine on responses to field stimulation and to noradrenaline in vas deferens and anococcygeus muscle of the rat. The effects of phentolamine (10(-6)M) and prazosin (10(-7)M) on contractile responses, in the presence of cocaine or nortriptyline, were investigated in vas deferens and anococcygeus muscle of rat. Cocaine (10(-5)M) and nortriptyline (10(-6)M) had no effect on maximum responses to field stimulation, (--)-noradrenaline, methoxamine, and acetylcholine in anococcygeus muscle. However, both cocaine (3.3 x 10(-5)M) and nortripthline (10(-6)M) potentiated maximum responses to (--)-noradrenaline without altering the maximum response to field stimulation in vas deferens. In vas deferens, phentolamine potentiated or inhibited the responses to field stimulation depending on the frequency whereas prazosin inhibited all responses to field stimulation. In anococcygeus muscle, both phentolamine and prazosin inhibited all responses to field stimulation. In vas deferens and anococcygeus muscle, prazosin was a more potent antagonist of responses to (--)-noradrenaline than phentolamine. These results show that prazosin is a more potent postsynaptic alpha-adrenoceptor antagonist than phentolamine and suggest that prazosin has little or no affinity for presynaptic alpha-adrenoceptors.


Studies on the monoamine oxidase and catechol-O-methyltransferase of the rat cerebral microvessels. The rat cerebral microvessels were isolated and assayed both for monoamine oxidase (MAO) and catechol-o-methyltransferase (COMT) activities. Cerebral microvessels and brain filtrate were found to contain both forms (A & B) of MAO. On a per mg protein basis, the cerebral microvessels contained the greatest activity of MAO and COMT  than that of brain filtrate and mesenteric artery. Chemical sympathectomy using 6-hydroxydopamine neither decreased total MAO activity, nor the A form of the enzyme, nor did it have any effect on COMT activity in the brain microvessels. These results suggest that COMT and both forms of MAO in the rat brain microvessels are extraneuronal in origin.


Effect of oral and intravenous propantheline bromide on pentagastrin-stimulated canine gastric secretion. The gastric antisecretory efficacy of propantheline bromide (PB) as a function of the route of administration was studied in dogs equipped with chronic gastric fistulae. Sectetion was near-maximally stimulated by continuous intravenous (i.v.) infusion of pentagastrin. PB was administered either intragastrically (i.g.) or intravenously as a single bolus dose at the steady-state plateau of gastric secretion. The administration of PB produced a dose-dependent inhibition of gastric secretion (water and acid output). Gastric acid concentration was not appreciably inhibited by PB. The dose-response (inhibition of acid output) curves for i.g. and i.v. administered PB were parallel. The potency (fiducial limits) of i.v. relative to i.g. administration was found to be 0.002 (0,0006--0,0051) when the i.v. value was taken as unity.


Effect of substance P on mechanical and myoelectrical activities of stomach and small intestines in conscious dog. The effect of Substance P (SP) on the intestine in situ of the dog was investigated. Five female dogs were used. At the same time, mechanographic recordings, using balloon kymography, were taken, while the myoelectric activity was recorded by means of electrography. Differences in SP action on the mechanogram and electromyogram of the stomach and the small intestines were reflected in the following phenomena: (a) SP in the doses used was less active on the ileum than on the stomach; (b) SP increased basal tonus but inhibited peristaltic contraction; (c) SP acted predominantly on spike discharges in the electromyogram. These results are likely to support the assumption that SP acts as a physiological modulator of smooth muscle activity.


Effect of butorphanol and morphine on pulmonary mechanics, arterial blood pressure and venous plasma histamine in the anesthetized dog. Butorphanol, levo-N-cyclobutylmethyl-3, 14beta-dihydroxy-morphinan, is a new agonist-antagonist type analgetic agent which is 4 times more potent than morphine in experimental animals. Equianalgetic doses of butorphanol and morphine were compared, following rapid intravenous injection to anesthetized dogs, for their effects on pulmonary resistance, dynamic compliance, arterial blood pressure and venous plasma histamine levels. Butorphanol, 0.75 mg/kg, had no effect on pulmonary resistance, dynamic compliance or  venous plasma histamine levels. Morphine, 3 mg/kg, increased pulmonary resistance, decreased dynamic compliance and elevated venous plasma histamine levels. Both drugs decreased arterial blood pressure but the hypotensive effect of butorphanol was significantly less in magnitude than that of morphine. Pretreatment with chlorpheniramine antagonized the effects of morphine on pulmonary resistance, dynamic compliance and arterial blood pressure. These results suggest that in man butorphanol may have less potential than morphine for causing airway constriction, hypotension and histamine release.


Urinary methylhistamine as an index of histamine formation during histidine decarboxylase inhibition in the rat. A new method is described for the evaluation in vivo of histidine decarboxylase inhibitors. Urinary methylhistamine excretion is approximately trebled in rats treated simultaneously with the histaminase inhibitor aminoguanidine and the monoamine oxidase inhibitor pargyline, thus providing a high base-line against which inhibiton of methylhistamine formation, and hence of histamine formation, can be measured. Variations in the recovery of methylhistamine are compensated for by addition of a standard amount of radioactive methyl-histamine to each urine sample. The method has the advantage over previously described methods of requiring less radioactive material and fewer animals which, moreover, do not have to be killed and so can be re-used. In addition, the time course of inhibition can be assessed.


Comparison of neuromuscular effects and acute toxicity of some aminoglycoside antibiotics. The correlation between acute toxicity and the effects occurring at neuromuscular junction level of some aminoglycoside antibiotics was investigated. Netilmicin (Sch 20569), sisomicin, gentamicin and kanamycin were administered i.v. in the rat and the following effects were studied: neuromuscular blocking activity (sciatic-gastrocnemius preparation), and acute toxicity evaluation. Neuromuscular blocking effects were found to be well correlated to acute toxicity data for all test-antibiotics. Comparison of results gave a sequence of relative potency which was as follows: netilmicin = sisomicin greater than gentamicin greater than kanamycin. Our findings confirmed that both respiratory failure, reporter as a side effect of the clinical use of aminoglycosides, and experimental toxicity follow the neuromuscular block.


Chemotherapy of acute leukemia: a comparison of vincristine, cytarabine, and prednisone alone and in combination with cyclophosphamide or daunorubicin. Adults (274) with acute leukemia (AML) were randomly assigned to one of three treatment regimens: vincristine, prednisone, cytarabine--(1) 100 mg/sq m/day with cyclophosphamide (COAP); (2) 100 mg/sq m/day with daunorubicin (DOAP); and 200 mg/sq m/day (OAP). Cytarabine was infused continuously for five days. Patients entering complete remission randomly received maintenance treatment with COAP or OAP. For 197 previously untreated AML patients given COAP, DOAP, or OAP, remission rates were 37%, 35%, and 43%, respectively; median lengths, 40, 45, and 90 weeks; median survival, 7, 11, and 8 weeks. No statistically significant difference was found among treatments. Therefore, adding cyclophosphamide or daunorubicin, or using the COAP regimen with continuously infused cytarabine, produced no significant improvement over previously reported regimens. There was no significant difference in remission lengths in previously untreated AML patients maintained on OAP (median 81 weeks) or COAP (median 65 weeks).


Anticoagulation in renal vein thrombosis. Long-term anticoagulation therapy was evaluated in two patients with renal vein thrombosis and the nephrotic syndrome. Neither patient exhibited peripheral thromboemboli. Moreover, the renal vein thrombus resolved in both cases after eight months on a regimen of oral anticoagulant therapy. Glomerular filtration rate remained stable despite persistence of the nephrotic syndrome. These results suggest that long-term anticoagulation may be of distinct value in nephrotic patients with renal vein thrombosis.


Transmural myocardial infarction with the prolapsing mitral-leaflet syndrome and normal coronary arteries. Clinical and electrocardiographic evidence of transmural myocardial infarction developed in two patients (a woman, age 38, and a boy, age 17) with prolapsing mitral-leaflet syndrome. Both had normal coronary angiograms and normal plasma lipid levels. Left ventricular angiography showed dyskinetic areas in both patients. Coronary artery embolism or prolonged coronary artery spasm may have been the underlying mechanism of production of myocardial infarction.


An automated verbal medical history system. Computer-based automated medical history acquisition systems have not been as widely utilized as originally anticipated. The high cost, limited accessibility and alien nature of the computer terminal equipment have all been cited as important factors in the limited acceptance. A system has been developed that makes it possible to use a standard household telephone as the computer input and output terminal in obtaining medical history data. Patient acceptance is excellent, and medical information gathered using this technique is as accurate as that obtained by self-administered questionnaires or personal interviews. This system maintains the advantages of the terminal-based automated history program while eliminating many of its deficiencies.


Spontaneous hypoglycemia in chronic renal failure. Spontaneous fasting hypoglycemia developed in four nondiabetic patients with end-stage renal failure. All were undergoing long-term maintenance hemodialysis and three patients were anephric. Hypoglycemia was generally accompanied by severe metabolic acidosis and, in three patients, lactic acidemia. Abnormalities of hepatic structure and/or function were present in three patients. In one patient, hypoglycemia was refractory to exogenous glucagon, failed to respond to alanine, glycerol, or galactose, and was associated with suppressed plasma insulin and elevated plasma glucagon levels. Fasting hypoglycemia appeared to result from several mechanisms. In at least two patients, fasting hypoglycemia and lactic acidosis resulted from impaired hepatic gluconeogenesis in association with impaired or absent renal glucose production. Additionally, substrate limitation probably contributed to hypoglycemia in several patients.


Prostatic abscesses involving anaerobic bacteria. Anaerobic bacteria have seldom been reported in prostatic abscesses. The present study concerns four cases in which the exudate was cultured with optimal microbiological techniques. Our results showed a complex aerobic-anaerobic flora in each instance, with a total of 21 isolates, including seven aerobes and 14 anaerobes. This experience has important implications concerning culture practices and empiric antimicrobial treatment for patients with prostatic abscess.


Progressive dialysis encephalopathy from dialysate aluminum. Progressive dialysis encephalopathy was observed as a frequent complication (eight of 34 patients) in a small hemodialysis unit. After the water used for dialysis was deionized, no further cases of encephalopathy developed in 29 patients. In the absence of other apparent changes in therapy, this significant difference in incidence (P less than .005) is considered to be the result of reduction in unusually high water aluminum levels from 0.637 mg/liter to less than 0.001 mg/liter by use of a deionizer.


Treatment of central diabetes insipidus in adults and children with desmopressin. Modification of the natural vasopressin molecule to form desmopressin acetate (DDAVP) resulted in a compound with prolonged antidiuretic activity and virtual elimination of vasopressor activity. Twenty-one patients with central diabetes insipidus who ranged in age from 3 to 68 years were treated with DDAVP, which was administered intranasally in a dosage ranging from 10 microgram every 12 hours to 20 microgram every eight hours. Effective control of symptoms was obtained in all cases. There were no consequential toxic effects. As previously reported, DDAVP appears to be the preferred drug for the management of central diabetes insipidus. Biochemical alteration of hormones may enhance desired therapeutic activity and eliminate toxic effects. The development of DDAVP is an example of the potential for development of useful therapeutic peptides.


Marginal benefit of renal biopsy in systemic lupus erythematosus. The predictive information provided by renal biopsy was assessed for four systemic lupus erythematosus (SLE) patient populations and compared with the predictive information from clinical data without benefit of biopsy, both measured against actual outcome. Renal biopsy results, whether studied by light or electron microscopy, contain important prognostic information. However, the prognostic information from renal biopsies in these patient groups is generally less than that of even the simplest clinical classifications; and when combined with clinical information, the total prognostic content is essentially that of the clinical information alone. Thus, judged by presently available data, the renal biopsy in SLE provides mainly redundant prognostic information. The marginal benefit is the difference between what is known before and after a test. Quantitation of predictive accuracy allows assessment of marginal benefit, that is, the increment in accuracy afforded by an additional test. Costly and potentially hazardous procedures, such as renal biopsy, require reassessment in terms of marginal rather than absolute predictive ability.


The pathophysiology and treatment of gastroesophageal reflux disease: new concepts. In summary, the recent understanding of the pathogenesis of gastroesophageal reflux disease as owing to LES incompetence has led to improvement in both the diagnosis and the treatment of this disorder. Diagnosis now dependent on demonstrating the presence of reflux, an incompetent sphincter mechanism, or some complication of reflux. Treatment is focused on reducing the endogenous factors that contribute to reflux, or actually restoring the sphincteral barrier to reflux by pharmacologic or surgical means.


Recurrent herpetic whitlow due to herpes simplex virus type 2. Herpes simplex virus type 2 was demonstrated to be the cause of a recurrent painful and disabling digital infection in a young man. It is possible that this was originally venereally transmitted. With increasing incidence of genital herpes infections, digital herpetic infections may become more common in the nonmedically employed community.


Red blood cell casts in acute interstitial nephritis. A 45-year-old woman receiving hydralazine and hydrochlorothiazide therapy was found to have a reduced glomerular filtration rate, a positive antinuclear antibody reaction, and RBC casts in the urinary sediment. Glomeruli with normal morphology (light, immunofluorescence, electron microscopy) were found on renal biopsy; however, a mild interstitial nephritis was observed that predominantly involved the distal tubules. The etiology of this inflammatory process is unknown. Changes in distal tubular function correlated with the morphology: acidification was impaired whereas concentrating ability was normal. Although RBC casts have been thought to be diagnostic of glomerular diseases, the present case demonstrates that tubulointerstitial disease can be responsible for RBC cast formation.


A case of coccidioidomycosis with unique clinical features. Primary coccidioidomycosis, occurring in a microbiologist whose initial symptoms were cough, fever, night sweats, and chest pain, was unique, because for six months following infection his sera remained nonreactive, and his chest roentgenograms showed no lesions. Throughout this period, his sputa continued to yield Coccidioides immitis. His skin test, which showed negative results 12 days after the onset of symptoms, became positive for coccidioidomycosis eight months later. Spherule formation by C immitis cultures was demonstrated in human pleural fluid medium at 40 degrees C within four to six days and in the internal organs of a mouse inoculated with an arthrospore suspension. After six months of rest and without specific antibiotic treatment, the patient's sputa became negative and his clinical recovery was complete. We emphasize culture isolation and accurate identification of C immitis in diagnosis, and serology in the assessment of therapy.


Late deterioration in tetralogy of Fallot: unusual findings and successful correction. A patient with tetralogy of Fallot who underwent a successful Blalock shunt procedure as a child was evaluated 28 years later because of clinical deterioration. Results of cardiac catheterization and angiography disclosed, in addition to a functioning shunt, evidence of an infundibular, subvalvular tumor and a large anastomosis between the left circumflex coronary artery and the bronchial arteries of the right lung with the possibility of "coronary steal". At operation, the Blalock and coronary-to-bronchial artery anastomoses were ligated; and total correction was performed including resection of the pulmonary valve and infundibulum, excision of the tumor, closure of the ventricular septal defect, and application of an outflow patch to enlarge the pulmonary annulus. The patient was discharged nine days after surgical correction.


Treatment of ruptured interventricular septum with afterload reduction. Two patients with a ruptured interventricular septum complicating acute myocardial infarction were treated with isosorbide dinitrate. The first patient recovered from cardiogenic shock after sublingual administration of 5 mg of isosorbide dinitrate every two hours and was successfully operated on. The second patient recovered from severe pulmonary edema during the acute stage of the infarction with sublingual isosorbide dinitrate. Moreover, she experienced a considerable symptomatic improvement when a 5 mg sublingual dose of isosorbide dinitrate every three hours was added to her long-term treatment. Analysis of hemodynamic data showed that the most striking change following administration of the drug was the substantial reduction of pulmonary wedge pressure. The striking symptomatic and hemodynamic improvement was achieved by the favorable effect of afterload reduction on left ventricular performance and not by reduction in left to right shunt.


Cholesterol embolization: a complication of angiography. Cholesterol embolization is not widely recognized as a complication of major arteriographic procedures. In a retrospective study of 71 autopsies of patients who underwent diagnostic arteriographic procedures (20 with aortograms, 51 with cardiac catheterization and coronary angiography), we found an incidence of cholesterol embolization of 30% and 25.5%, respectively, in comparison with 4.3% in an age and disease-matched control population. The organs most frequently affected are the kidney and spleen following aortogram, and the myocardium following cardiac catheterization. The clinical importance of these findings cannot be ascertained from this study, but our experience with a single case demonstrates that radiographic studies may produce substantial morbidity.


Primary aldosteronism presenting as myoglobinuric acute renal failure. Hypokalemia is an uncommon cause of rhabdomyolysis with acute tubular necrosis. We recently treated a patient in whom severe hypokalemia attributed to diuretic therapy antedated acute myoglobinuric renal failure by six months. After recovery, hypokalemia persisted and subsequent evaluation disclosed primary aldosteronism. This case is a unique presentation for primary aldosteronism and illustrates the importance of diagnosis before treatment in hypertension as well as the hazards of hypokalemia.


Otomycosis due to coccidioidomycosis.

Otomycosis due to coccidioidomycosis. The course and treatment of two patients with otomycosis due to Coccidioides immitis, believed to be the first such cases reported, are described. Both infections appeared due to reactivation of hematogenously disseminated foci. Local and systemic chemotherapy plus surgery resulted in remission, and host immune response also appears to be an important factor. One patient, with systemic lupus erythematosus, required more extensive surgery, more chemotherapy, and reduction in steroid dose to arrest the disease. A combined surgical and chemotherapeutic approach appears necessary when otomycosis is due to invasive fungi such as C immitis.


[Inquiry on the future of newborns treated in intensive care units for children. III. Neurologic anomalies]. This study concerned newborns admitted between 0 and 10 days of life at the intensive care unit of the Hospital St-Vincent-de-Paul from 1969 to 1972. They were followed later as outpatients. Out of 1,607 newborns admitted, 1,126 survived (average mortality: 30%). 532 were examined after one year, 397 after two years. On the whole prognosis may be considered as good: at 2 years of age, 8% had major neurologic abnormalities; 4% minor abnormalities, no increase in the percentage of major neurologic abnormalities between 1969 (6%) and 1972 (5%), whereas mortality decreased from 36 to 24%. The various types of neurologic deficits were analyzed, according to their effects on rehabilitation (4% had severe retardation, 11% moderate retardation). The sensory involvement (3%) and intercurrent seizures (10%) were also analyzed. According to the bias of the Unit in recruitment, this enquiry concerned children close from term or medium premature children (B.W. 1,500 g) : this diminishes the true rate of the neurologic deficit. The relationships between etiology of neonatal distress and delayed neurologic abnormalities are emphasized.


[Evaluation of one year experience with cerebral tomodensitometry in pediatric neurology]. Cerebral tomography allows the delineation of areas modified by edema or necrosis, the visualization of calcifications undetectable by standard x-ray examination, extra- or intra-cerebral blood effusions and neoformations of the cerebrum or of its envelopes. It also reveals slight or localized cerebral atrophies that other neuro-radiologic techniques sometimes failed to detect. It appears therefore worthwhile to reconsider pediatric neurology according to this new type of investigation. Its sole difficulty in young children, is the requirement of a half hour immobility, best obtained by general anesthesia. However, the rapid improvements of this technique will probably permit to overcome this slight drawback.


[Colonization by enterobacteria during the first week of life in the normal newborn]. The colonisation by enterobacteria of neonates, born normally, has been studied by quantitative and qualitative techniques (by the determination of the differing patterns of antibiotic resistance). The resistant enterobacteria were less common than the sensitive strains but resistant ones were widespread in the first week of life and 6 out of 10 babies became carriers of Klebsiella. The results enabled epidemiological observations to be made (the role of the mother, who only seems to be important during delivery, and the importance of the bacteria carried on the hands of the staff), and to assess the effect of antibiotics in hospital even if they are not given to the baby.


[Acute nalidixic acid poisoning in children]. A 31 month old child developed seizures 30 minutes after the accidental ingestion of toxic quantities of nalidixic acid. The case is unusual because of the age of the patient and the circumstances of the poisoning. It emphasises that this drug is contraindicated in children with previous neurological disease.


[Postnatal iodine excess with hypothyroidism and respiratory pauses. Danger of the cutaneous application of iodine chemicals]. A hypothyroidism with moderate goiter was discovered in a newborn presenting with repeated apnoea indicating a severe risk of sudden death. The mother was given no iodine-rich drug. However, the child was submitted to several large applications of iodized alcohol to the skin for numerous blood samplings. Treatment with thyroid extract resulted in the disappearance of the respiratory pauses and return to euthyroidism within 3 months.


Psychic distress, life crisis, and use of psychotherapeutic medications: national household survey data. Findings are reported from a nationwide survey of a cross-section probability sample (N = 2,552) of US adults. Data on psychic distress were obtained from a shortened version of the Hopkins symptom checklist, data on life crises from a shortened version of the Holmes-Rahe social readjustment rating scale. Methods for collecting data on use of psychotherapeutic medications were validated in a separate study. Data are presented on the prevalence of high levels of psychic distress and life crisis among various age, sex, and other demographic subgroups; on the relation between life crisis and psychic distress; and on the relation of life crisis and psychic distress to use of psychotherapeutic medications and alcohol. The findings suggest an illness behavior model for the use of psychotherapeutic medications in outpatient practice, and the lend little support to a "self-indulgent consumer" interpretation.


The familial prevalence of anxiety neurosis. A family history study of 112 anxiety neurotics and 110 surgical controls showed that the morbidity risk for anxiety neurosis among first-degree relatives of neurotics was 18% compared to 3% among control relatives. Relatives of anxiety neurotics were also shown to be at higher risk for the development of alcoholism. Female relatives were found to be at greater risk than male relatives, reflecting their increased susceptibility to the illness. These data confirm previous findings of an increased familial prevalence of anxiety neurosis.


Plasma levels of chlorpromazine in schizophrenia; a critical review of the literature. Measurment of chloropromazine and metabolite levels in the blood has not yet developed such that it can help the clinician. Apart from their chemistry, the clinical aspects of the experimentql design of most studies leave much to be desired, so that it is not possible to draw any overall conclusions about the relationship between chlorpromazine blood levels and clinical outcome from the data currently available. Measurement of response to a single test dose may prove potentially more fruitful in predicting outcome and in establishing drug and dosage choice for a given patient than simple attempts to correlate sustained dosage levels with clinical response. For chlorpromazine, indeed for any drug, it would seem wise in the first instance to focus clinically well-designed studies on the parent substance, rather than launching into more costly, but clinically unsophisticated, studies of its metabolites.


Test dose response in schizophrenia: chlorpromazine blood and saliva levels. A gas chromatographic/mass spectrometric method for measuring chlorpromazine using 2H6--labeled chlorpromazine as an internal standard has the potential for considerable precision and specificity. Results are reported of chlorpromazine levels in plasma and saliva after administration of a single test dose to 13 schizophrenic patients in a tightly designed experiment. There was a clear and substantive relationship between blood and saliva levels of chlorpromazine, both following a typical decay curve. Saliva and plasma levels were strongly associated for a particular patient, and there was even a strong consistency in saliva-plasma ratios between patients, with an overall statistically significant correlation between plasma and saliva levels for all measurement on all 13 patients. In general, it seems that saliva sampling has great potential as a simple noninvasive technique for investigation of chlorpromazine and other antipsychotic drugs in psychotic patients. Nevertheless, for the moment, it should be regarded as strictly experimental and not suitable for immediate clinical application.


Saliva lithium concentrations in the management of lithium therapy. To define conditions under which saliva lithium carbonate concentrations can be used as a guide in lithium therapy, serum (Cp) and saliva (Cs) concentrations were determined simultaneously under different circumstances in 12 patients receiving lithium, and the effect of seven variables for example, (sex, saliva flow rate) on the Cp:Cs ratio was examined. The average ratio was 0.57 if saliva was collected in the morning before breakfast and 0.45 otherwise. The Cp:Cs ratio was found to vary much more between individuals than within an individual. We propose a method that minimizes the effect of the interindividual variation on the error in the prediction of Cp from Cs by using one or two measured Cp:Cs ratios to adjust the individual ratio. Using this technique the Cs may be useful as a predictor of the Cp in monitoring lithium therapy.


The dose-response ratio in electroconvulsive therapy a preliminary study. To investigate pretreatment patient variables that might correlate with dose-response characteristics of electroconvulsive therapy (ECT) and treatment outcomes, 14 patients were assessed on a daily basis, before and during treatment, using self-report affective scales, three simple paper-and-pencil tests of cognitive function,and finger-tapping speed. From these data, dose-response ratios and treatment outcome measures were derived. The dose-response ratio of ECT was found to correlate with age--the younger the patient, the more favorable the ratio. This finding is discussed in terms of the known relationships between brain monoamine oxidase levels and age, and the established relationship between seizure duration and treatment efficacy. The dose-response ratio over the first two electroconvulsive treatments as well as lesser degrees of initial congnitive and greater degrees of initial affective impairment correlated strongly with greater overall affective improvement. Some clinical and research implications of these findings are discussed.


Academic psychiatry in the political marketplace. There is pressure for all medicine to be publicly accountable and for there to be public manifestations of professional responsibility. The expectation of an immediate return on the public's investment in education is matched by cries for"relevence" in research. The generation and transmission of psychiatric knowledge is not compatible with such a direct telelogic approach. Yet, public accountability is necessary, considering the public monies involved. Academic psychiatry should become familiar with the political marketplace--a high-pressure environment where fiercely competing interests vie for the politician's attention through votes and contributions, and where the "squeaky wheel gets the grease". Psychiatry can ill afford to adopt a passive posture in this political marketplace. Psychiatrists bear responsibility for informing the public about the relevance of psychiatric research and education. The profession must accept--even embrace--the concept of public accountability as a synchronous extension of our professional responsibilities.


Hazards of succinylcholine administration during electrotherapy. We describe prolonged apnea following electrotherapy in a patient who was also being treated with a topical organophosphate anticholinesterase, ecothiophate iodide (phospholine iodide), for glaucoma. The increased duration of action of succinylcholine resulted from low levels of serum cholinesterase that had been caused by the organophosphate. Attention is called to other drugs that directly or indirectly (by lowering serum cholinesterase) interact with succinylcholine chloride resulting in prolonged apnea. Other potential hazards of succinylcholine administration, such as hyperkalemia and cardiac arrhythmias, are also discussed.


[Test of O,O-dimethyl(1-hydroxy-2,2,2-trichloroethyl)phosphonate (Trichlorfon) for carcinogenic acitivity in rats by oral (oesphageal-gastric intubation) and intraperitoneal application (author's transl)]. O,O-Dimethyl (1-hydroxy-2,2,2-trichloroethyl)phosphonate (Trichlorfon) is produced at a large scale and used in many countries e. g. in agriculture and housholds to control insects and on animals to control parasties. The compound (dissolved in isotonic sodium chloride solution) was tested for carcinogenic activity in albino rats by oral (oesophageal-gastric intubation) and intraperitoneal administration. The period of treatment was 90 weeks. The experiment was terminated at 118 weeks. There was no statistically significant difference when the tumor incidence in the groups of treated and control animals was compared. No carcinogenic activity of the compound could be demonstrated in rats at either route of application.


An image analysing method for automated cytologic prescreening of cervix carcinoma and its prestages: demonstration and preliminary results. The image analysing method for automated cytologic prescreening is founded on the evaluation of epithelial cell nuclei in regularly stained and prepared smears. The technical equipment consists of a fast scanning microscope and a software-oriented computer. The device is able to isolate all objects present in the visual fields. Clumps, artefacts, detritus and other disturbing objects are eliminated. Among the cell nuclei the nonepithelial forms (histiocytes, leukocytes, lymphocytes) are distinguished from the epithelial ones. The latter are compared with a representative sample of normal epithelial cell nuclei, exactly classified by cytologists. All objects are described by 18 mathematically defined parameters. The results of classification is a statistical information on the probability of coincidence of an unknown case with the normal object sample. In addition the evaluation program provides the number of automatic isolated cell nuclei. By these informations it is possible to differentiate between positive (tumor-suspicious), negative and inadequate smears.


[The microscopy fluorometry (author's transl)]. The microscope photometry and the method of continuously recording photometry help in the exemplification of the temporal development of virus multiplication and in providing information on the localization of the antigen in cells. Furthermore an automatic fluorometric microscope photometer (AFM) is described. By this method, the titre and that dilution required for the complete detection of antigens can be determined and an objective comparison of the various conjugate specimens is possible.


Pulse cytophotometric measurements on tumor cell suspensions and exfoliative material. By impulse cytophotometry (ICP) it is possible to get a DNA-distribution curve of nuclei in cell suspensions. The ICP curve directly represents the ploidy pattern of the investigated cell population and, more indirectly the proliferation intensity. For practical tumor diagnosis in cytology by ICP as a first step we must know, wether the ICP is able to detect differences between normal and tumor cells by simple criteria. Together with our clinical coworkers we had investigated cell suspensions from carcinomas of the cervix, ovary, breast, larynx, stomach and malignant melanomas. Approximately one half of these tumors were poly- or aneuploid. In the remaining diploid tumors some did not show signs of strong proliferation in the form of high 4c-peaks in the ICP; for these the chances of detecting by ICP in exfoliative material are low. This is in agreement with our results on vaginal smears. Here we had a good correlation between the mean 4c-height of the ICP curves and the Papanicolaou grading. But mass screening is not the main application of ICP because the security of Pa-grading is more sufficient. In individual problematic cytological cases with repeated investigation ICP is a very valuable diagnostic aid.


[Diagnostic by angiography of soft tissue tumors of the extremities (author's transl)]. The diagnostic efficacy of angiography in soft tissue tumors of the extremities (15 malign, 16 benign) has been examined. Each of the malignant processes could be diagnosed correctly. We obtained two wrong positive results in chronic inflammatory processes. Both cases showed several angiographically malignant criteria.


Activity of some lysosomal hydrolases in the homogenates of transplantable melanotic and amelanotic melanoma in golden hamster (Mesocricetus auratus, Waterhouse). Activity of arylsulphatase, beta-glucuronidase, cathepsin D, and acid phosphatase in the homogenates of melanotic and amelanotic melanoma was determined. The activity of these enzymes is higher in melanotic than in amelanotic melanoma. Respective values for melanotic and amelanotic tumours are: arylsulphatase 10,78 +/- 3,20, and 1,45 +/- 0,66 micron 4-nitrocatechole/mg protein/hr; beta-glucuronidase 11,10 +/- 1,40, and 9,98 +/- 1,35 micron phenolphthalein/mg protein/hr; cathepsin D 4,24 +/- 1,37, and 3,26 +/- 0,73 micron tyrosine/mg protein/hr; acid phosphatase 230 +/- 22, and 180 +/- 25 micron p-nitrophenol/mg protein/hr. These differences are statistically significant. The increased activity of the lysosomal enzymes in melantoic melanoma probably depends on the occurrence of an higher number of lysosomes in tissues containing melanins.


[Recent results of intraoperative cytodiagnosis in thoracic diseases (author's transl)]. The intraoperative cytological quick-examinations and quick-tests may influence way and type of the operation in cases of uncertain nature. They may lead to the fact that the original schedule of operation is kept to or changed. Thus, the operation is performed according to the situation, and lung tissue may be saved. Therefore, the possibility of a rapid diagnosis during the operation is of great importance. It is, however, often difficult or risky due to a potential tumour transplantation or due to other complications, to obtain respective tissue material for histological examination, above all, in such cases where the foci are located very deeply in the lung parenchyma. Therefore, the authors deal with the cytological examinations of 216 tissue samples taken from 187 patients intraoperatively (obtained by thoracotomy: 119 cases, by mediastinoscopy: 57 cases, by various surgical interventions: 20 cases). In 155 cases (82 per cent) the findings proved to be rightly positive or negative with regard to their malignity. The histological type diagnosis was correct in 79 per cent of all tumours. In 94 per cent of the nonmalignant processes the cytological finding was negative; besides, the authors point to the histological diagnosis of several types of benign tumours, Boeck-sarcoidoses, tuberculoses, other granulomatoses etc.


[Contributions to the morphological basis of the cytology of the respiratory tract (author's transl)]. It is reported on 275 cases treated for bronchial carcinoma at the Surgical Departement of Düsseldorf University between 1970 and 1974. In all cases cytological as well as histological methods were used for diagnosis. These cases are complemented by 60 cases selected under cytological aspects from other sources. Localization by X-ray proved a central tumor in 11% and tumors in the different lobes in 89% of the cases. Tumors were more frequent in the upper lobes (54%) than in the lower lobes (30%), and more frequent in the right lung (58%) than in the left (42%). Cytological smears were positive or suspicious in 77% of the central carcinoma and in 60 and 56% in cases of roentgenologically peripheral localization. There is no difference found between tumors in the upper and lower lobes. Bronchial secretion renders less positive results for all histological types. This indicates a small area of origin for the cells investigated by this method. Metaplastic cell changes were observed in one third of all cases involving all histological types equally. Operation was possible in only 30% of the cytologically diagnosed cases in comparison to 52% of all cases. The 60 selected cases were composed of 48 primary and twelve secondary tumors. Probatory excision had been performed in 50%, 8% remaining negative even after repetition. 33% could only be verified by autopsy corresponding to 29% with sputa, bronchial aspirate and pleural effusion positive at the same time and therefore regarded as late stages. Negative results can be caused by fibrosis as well as obstruction, fibrosis not being a regular result of treatment with X rays. Differentiation of tumor types is possible in cytological smears. Sometimes differences in the same tumor are evident and occasionally the tumor type can be more distinct in the cytological preparations. Metastatic tumor cells are open to false classification. Tumor and tuberculosis were found in four of sixty cases. One false positive result was caused by cells ressembling cases of experimentally induced bronchiolization of alveoli by different noxa.


[Problems of pulmonal cytology sent in from far (author's transl)]. The probability to find a correct diagnosis by cytological examination of sputum and other pulmonal specimens sent in to a cytological central laboratory far from comprehensibly seems to render somewhat lower than by histologically examining tissues. The cytologist must try hard to avoid false positive judgments, for the method soon falls into disrepute if false positive reports are sent out. The main source of false positive diagnosis seems to be a too subjective interpretation by the cytopathologist. Basal cell hyperplasia and atypical squamous metaplasia are the main morphologic alterations that may occasionally mislead even an experienced cytopathologist. Inquires to clinics and practice concerning an evaluation on value of sputum cytology to detect bronchogenic cancer proved a high appreciation of this method.


Cytological survey of bronchial brushings and aspirations performed during fiberoptic bronchoscopy. In this series of 342 cases of bronchial carcinoma diagnosed by fiberoptic cytology (brushing and aspiration), comparison with the endoscopic findings gave the following results:--As regards primary carcinomas, 91 per cent of the cases in which the tumour was visible had a positive cytology when brushing was used and 84 per cent with aspiration. 79 per cent of the cases with no visible tumour but with suspicious changes of the bronchial wall had a positive cytology with brushing and 71 per cent with aspiration. When no abnormality could be seen by fiberoptics, positive cytologies dropped to 47 per cent and 50 per cent respectively.--In case of metastatic carcinoma the results are not as good. However, brushings gave 87 per cent positivity when the tumour was visible with the fibroscope and aspiration 75 per cent. Such cases are rather unfrequent unfortunately. Suspicious lesions at the fibroscope examination yielded respectively 68 and 64 per cent positivity. While in cases with no abnormality seen with the fibroscope brushings gave a 29 per cent positivity and aspirations a 25 per cent. No false positives were made. Correlation with histology and comparison with sputum cytology will be commented upon.


[Histogenesis of adenomas of the parathyroid gland]. The similarity of adenomas of the parathyroid gland with other tumours of the APUD-system elements was investigated. The structure of 10 adenomas was studied. The ultrastructural characteristics were compared with the histological structure of the tumour. Various histological variants of the neoplasias were shown to have similar ultrastructure. The tumour tissue was represented by clear transitional and dark cells. In their cytoplasm, osmiophilic granules of the secrete, villae, laminar structures resembling Nissl bodies, fine granular and fine fibrous substances, and lipid inclusions were found. The structural similarity of adenomas with other endocrine-active tumours developing from cells of the neuroectodermal origin (carcinoids, paragangliomas, etc.) was noted. It is suggested that parathyroid glands belong to the APUD-system.


[Cytopathology of bronchial tree secretions in bronchial asthma patients]. The methods of clinical cytology were used for examination of 64 patients with bronchial asthma (42 men and 22 women). Six patients were found to have an atopic form of asthma, 58--the infectiousallergic form. The material for a cytological examination was obtained by bronchoscopy. Early in the exacerbation stage and in patients with a relatively short duration of the disease the cytopathological pictures of the bronchial secretion are characterized by a relatively insignificant pathology of the cell composition. In cases of a long-term disease, great changes in the morphology of the cells and the pattern of the cytograms are observed up to the appearance of cell forms with marked signs of atypicity.


[Morphologic features of erythrocytes in normal subjects and in anemia caused by lead poisoning (electron microscopic study)]. The methods of scanning and transmission electron microscopy were used to study erythrocytes from normal subjects and those suffering from anemia of lead poisoning genesis. Erythrocytes from normal subjects were shown to have predominantly convex-concave and biconcave shapes. An insignificant portion of ageing erythrocytes of spherical shape and decreased volume had granular surface and consolidated hemoglobin. Normally, in addition to the above-mentioned cells, erythrocytes with an abnormal relief occur: with perforating openings, crypt-like recesses, tubercles and processes. In anemia, the number of atypical erythrocytes increased many-fold. The process of sequestration and fragmentation of hemoglobin-containing particles is one of the mechanisms of anemia development.


[Morphologic changes in the nervous system in acute oral poisoning with dichloroethane]. The nervous system of 14 patients dying of acute oral poisoning with dichloroethane was examined morphologically. Considerable vascular disorders (perivascular edema, congestive plethora, vascular dystony, small focal hemorrhages) and diffuse changes in the cerebral cells were found. The main forms of parenchymatous changes in the brain and spinal cord were acute swelling, shrinking, severe disease and ischemic changes in the nerve cells which occurred within 3--6 hours after taking dichlorethane. Pathomorphology of fibers of the spinal cord and peripheral nerves was presented by moderately marked myelin degeneration.


[Effect of pyridoxylate on the intensity of changes in the internal organs and skeletal musculature of rats under considerable physical loading]. Under considerable physical load, marked enzymopathy, increased permeability of cellular membranes with the involvement of cellular and subcellular structures develop in the myocardium, skeletal musculature and viscera of rats. Administration of pyridozylate decreases the intensity of damage reactions and normalizes to a certain degree the structure of cellular and subcellular elements of tissues. This indicates the advisability of the employment of the cell respiration regulators under conditions of general and tissue hypoxy and metabolic shifts.


[Renal actinomycosis].

[Renal actinomycosis]. A case of actinomycosis of the kidney in a man of 69 is described. The autopsy revealed a pyo-destructive process in the right kidney and paranephria with melting of the surrounding tissues and formation of fistulas. Histologically, a destructive variant of the development of actinomycotic granulomas with degenerating druses of the ray fungus and mycelial inclusions was revealed. This case may be classified as the primary form of actinomycosis.


[Method of performing an autopsy without cutting into the thorax or dissecting the ribs]. Two variants of autopsy of cadavers without cutting of the thorax and dissection of the ribs are described. The method is principally based on the transversal cutting of the abdominal wall alongside both hypochondria, severing of the diaphragm and exposure of a complex of organs (after preliminary removal of the intestine and spleen). In the first variant of autopsy, the upper part of the complex is crossed in the thorax at the level of the upper aperture of the thoracic cavity, leaving the organs of the neck without autopsy. In the second variant, no such crossing is done and the complex is removed together with the organs of the neck and the tongue (that is, the autopsy is complete). To separate the latter, an additional transversal supraclavicular cut about 10 cm in length is made. The advantages of these variants lie in the cosmetic effect.