Inheritance of Q and C band polymorphisms. Sequential Q and C banding of chromosomes from 36 individuals in three unrelated families revealed Q band variants on 6 different chromosomes and C band variants on 14 different chromosomes. These variants were inherited in Mendelian fashion with one excpetion in which a C band variant absent in the parents was found in a child. Although some of the Q band variants were also detected with C banding, there was no consistent correlation between the intensity of variant Q and C bands.


Structural rearrangements of chromosomes in the domestic chicken: experimental production by X-irradiation of spermatozoa. In order to produce chicks heterozygous for structural aberrations of chromosomes, 67 hens were inseminated with semen that had been exposed to 1200 R of X-rays. A sample of 204 chicks was hatched and survived. Among these, 18 (8.9%) contained rearrangements comprising 19 translocations and one pericentric inversion. All 10 males and eight females heterozygous for rearrangements were fertile and transmitted these rearrangements to approximately half their hatched progeny. Each of the major chromosomes of the chicken karyotype, except number 6, was involved in one or more of the translocations. The pericentric inversion was of a segment of chromosome number 2.


Trisomy 12 mosaicism in an infertile man. Cytological studies of peripheral blood lymphocytes from an infertile man revealed the presence of a mosaic trisomy 12. To our knowledge this has not been previously reported in patients. The clinical manifestations in this case enhance the interest of the cytological findings.


Evaluation of intraoperative biopsy of the pancreas. The authors carried out a retrospective review of intraoperative biopsy of the head of pancreas in 47 patients. Vim-Silverman needle biopsy (32 patients), or wedge biopsy (9 patients), or both (5 patients) were used. The correct diagnosis in the 34 patients with carcinoma was made in 76% by paraffin section and in 65% by frozen section. Diagnositic accuracy was 77% with needle biopsy and 38% with wedge biopsy. Complications occurred in six patients and consisted of pancreatitis, fistula and hemorrhage. Two patients required reoperation because of hemorrhage. The case of one patient who died of a pancreaticoperitoneal leak at the biopsy site is described in detail. The overall complication rate was 15%. These results indicate that wedge biopsy carries significant risks and frequently does not detect carcinoma. Needle biopsy is relatively safe and is more likely to provide an accurate diagnosis of carcinoma.


Rupture of the diaphragm resulting from blunt trauma in children. Rupture of the diaphragm due to blunt trauma is rare in the pediatric age group. This article describes six such cases. This life-threatening condition should be suspected in the case of any serious thoracoabdominal trauma, even in the presence of negative radiographic findings on initial evaluation. In the very sick child, horizontal beam, lateral radiographs of the chest and abdomen have been extremely useful in establishing the diagnosis. The suspicion and investigation of associated diaphragmatic injury will result in earlier diagnosis and treatment.


Epidermoid cysts of the spleen.

Epidermoid cysts of the spleen. The authors report three cases of epidermoid cyst of the spleen. A squamous cell lining was found in all three. One patient had a history of antecedent trauma, and in the surgical specimen the gross and histologic features were compatiible with splenic damage. No hematologic alteration was recognized on presentation. Angiography and spleen scanning were valuable aids in the diagnosis. All three patients were well 1 year after operation.


Intestinal obstruction due to a defect in the omentum. An unusual cause of instestinal obstruction is described in a 46-year-old woman thought before operation to have Crohn's disease. The right colon and terminal ileum had passed through a defect that had developed spontaneously in the greater omentum and had remained in that position for at least 1 year. The bowel was reduced and the multiple defects in the omentum were repaired.


Evolution of emergency cardiac care in Canada. Acute myocardial infarction is the most common cause of death in Canada. Most deaths occur within the first 2 hours of the onset of symptoms, before the person seeks or is able to obtain medical aid, and are due to arrhythmias rather than massive myocardial damage. Effective electrical and drug treatment of arrhythmias has reduced the hospital mortality but not the community mortality. If mortality from acute myocardial infarction and other causes of sudden unexpected death is to be reduced substantially a major reorganization of emergency medical services is needed so that the benefits of the modern coronary care unit can be provided to the patient as rapidly as possible. Public education in basic life support procedures to sustain life until advanced life support aid arrives is the first step towards the development of a more effective system of emergency cardiac care.


Relation between pulsus paradoxus and pulmonary function in patients with chronic airways obstruction. The relation of pulsus paradoxus to chronic, stable obstructive disease of the airways has not previously been described. Pulsus paradoxus was observed in 66% of 68 patients with such disease but in none of 14 healthy individuals. There was a significant correlation between the degree of pulsus paradoxus and the forced expiratory volume in 1 second (FEV1) in the subgroup of patients with bronchial asthma but not in the subgroup with chronic bronchitis or emphysema, or both. There was no correlation between the degree of pulsus paradoxus and the degree of hyperinflation in either group. Hence factors other than hyperinflation contribute importantly to the decrease in systolic pressure that occurs at full inflation of the lungs.


Isolated odontogenic keratocyst.

Isolated odontogenic keratocyst. Although odontogenic keratocysts are benign they are often locally destructive and tend to recur after conservative surgical treatment. They must therefore be distinguished from other cysts of the jaw. Keratocysts possess outpouchings and microscopic daughter cysts from which recurrences may arise. Histologic examination is essential for diagnosis since the appearances on roentgenograms and at operation usually do not reveal the true nature of the lesion. Since many nondental surgeons and pathologists are unaware of odontogenic keratocysts a case is presented in which surgical treatment was originally conservative and finally relatively radical.


Heart-Alert: emergency resuscitation training in the community. One approach to reducing avoidable mortality from coronary artery disease is to provide resuscitation capability in the community. In Manitoba this is the function of the Heart-Alert program, sponsored by the Manitoba Heart Foundation. The program is based on public and professional education dealing with the recognition and immediate care of cardiac emergencies, including cardiopulmonary resuscitation (CPR). The three components to the program are (a) training in basic CPR for all health care and community rescue groups; (b) training in definitive CPR for physicians, critical care nurses and advanced emergency medical technicians; and (c) education of the public to recognize the signs of impending or actual cardiac emergencies and to take appropriate action to summon quickly an emergency rescue team.The initial emphasis of the program has been on developing an organizational structure and a training network for basic CPR. A corps of instructor-trainers and instructors has been certified to implement CPR training in the medical and community target groups. Developmental problems include problems of quality control, of providing for self-sustaining and continued expansion, and of evaluation of the overall results.It is suggested that widespread implementation of CPR training is facilitated by the incorporation of CPR into existing training activities, particularly those of the medical, nursing and other health care disciplines, those of community protection agencies such as police, fire and ambulance departments, and those of volunteer groups concerned with rescue work and first-aid. If the impetus, organizational structure and instructor training are provided by a strategic agency, wide dissemination of CPR training is then possible at relatively modest cost.


Health problems and health care for adolescents in residential facilities in Quebec. The health problems of 160 adolescents in four residential facilities of the Quebec social welfare court were studied. At the time of admission 44% had at least one problem requiring consultation with a specialist and 80% had an average of two problems requiring primary care. The medical records of 106 youngsters in two re-education centres were also reviewed and similar results were noted. The health services available, particularly physical examination and laboratory testing at the time of admission and arrangements for referral and follow-up were judged to be insufficient in most centres. Although society has taken custody of these adolescents, no one is responsible for their health care. Since February 1976 the social welfare court residential facilities and the network involved in the care of socially disturbed youngsters have been undergoing reorganization. Health programs and services ought to be part of this reorganization, and private physicians, hospitals and government each should have a role in the establishment and functioning of these programs.


General anesthesia in Eisenmenger's syndrome. The anesthetic management of a woman with Eisenmenger's syndrome undergoing abdominal hysterectomy with general anesthesia is described. Proper anesthetic management of patients with this syndrome depends on a knowledge of the pathophysiologic process and associated complications. The potential problems of systemic hypotension, pulmonary embolism and infective endocarditis are outlined. Sudden death is a common and pregnancy is a major hazard.


Utilization of an evening/night hospital: first two years of operation. This study examined the utilization of an integrated evening/night hospital by 234 psychiatric patients referred to the hospital during its first two years of operation. Neither age, sex, marital status, referral source or diagnosis were related to utilization. However, patients whose previous treatment involved traditional psychiatric care, either inpatient or outpatient, were less frequently admitted and less likely to complete the program once admitted, than were those patients reporting either day hospitalization or no treatment prior to their admission. There were steady increases in the number of referrals, number of different referring agents, average length of stay and average daily census as the program matured during the first two years of operation. While these data indicated an increase in the utilization of the evening portion of the program, there was a commensurate decrease in the utilization of the night portion of the program. As a result, the provision of overnight accommodation has been discontinued altogether.


Moral judgement and moral conduct in the psychopath. The relationship between moral conduct and moral judgment was investigated by comparing moral reasoning of a psychopathic sample from a maximum security hospital for the criminal offender with a similar inmate, nonpsychopathic sample, and a group of "normals". Psychopaths obtained significantly higher scores on the Kohlberg scale of moral judgment than either of the other groups, for whom no differences were found. Results suggest the hypothesis that lack of guilt feelings in psychopaths facilitate the achievement of higher levels of moral judgment.


On being therapeutic.

On being therapeutic. Psychotherapy is both an art and a science. The art deserves as careful study as does the science. In this paper the author puts forward the view that the effectiveness of psychotherapy is dependent to a marked degree upon certain innate characteristics of the therapist: these include his character structure, his personal values, and his spontaneous personality style. In order to explore this thesis, the author examines what has been written about some successful and well-known psychotherapists, by their patients, their colleagues, and their friends. He concludes that these therapists strongly evidenced the following characteristics: empathy and concern, caring and protectiveness, warmth, therapeutic forcefulness, expectation of improvement, freedom from despair, reliability, friendliness and respectfulness. It is felt that such factors in the therapist must be taken into account in order to achieve a view of psychotherapy which is not reductionistic.


Combination therapy for multiple myeloma. The effect of six different chemotherapy regimens were evaluated in 462 previously untreated patients with multiple myeloma. In comparison with other treatments, drug combinations that included vincristine and were given at 3-week intervals were associated with higher response rates and longer survival times. No gain was noted from the use of Adriamycin or from combinations of alkylating agents unless vincristine was given and the treatment intervals were short. Seventy-one responding patients were allocated at random to maintenance treatment with intermittent courses of either azathioprine--prednisone or a combination of melphalan--cyclophosphamide--carmustine (BCNU)--prednisone. The survival time was not prolonged with either maintenance treatment in comparison with that for responding patients continued on other therapies or on no therapy in previous studies. Attempts to reduce tumor was maximally with a change in the therapeutic modality, such as with immunotherapy or radiotherapy, remain to be evaluated.


Lack of effectiveness of combined 5- fluorouracil and methyl-CCNU therapy in advanced colorectal cancer. Fifty-two patients with advanced colorectal cancer were treated with a combination of 5-Fluorouracil (FU) plus methyl-1,3-cis (2-chlorethyl)-1-nitrosourea (MeCCNU). The treatment schedule program consisted of 5-FU, 300 mg/m2 i.v. bolus, daily for 5 days, repeated at 5-week cycles. MeCCNU was administered at a dose of 150 mg/m2 orally on day 1 of the initial 5-day course of FU and repeated at 10-week intervals. Eighty-four percent (44/52) of the patients with advanced measurable disease developed progressive disease by 4 months or one and a half cycles of therapy. Only two patients had definite partial regression of tumor over the period of observation. The median survival of all patients measured from the onset of treatment was 9 months and is comparable to literature reports of untreated advanced colorectal cancer. This therapeutic trial of combined FU and MeCCNU, employing a dose-schedule distinct from but comparable to previous studies has failed to confirm the substantial response rate reported by other investigators and reinforces the need for exploring new drugs and combinations of drugs in advanced colorectal cancer. The use of sequential plasma CEA determinations as a primary monitor of therapy is discussed in relationship to clinical trials and guidelines for determining significant quantitative changes in plasma CEA levels are recommended.


A phase I study of pyrazofurin.

A phase I study of pyrazofurin. Sixty-one patients with advanced disseminated cancer were given progressively increasing doses of pyrazofurin to evaluate toxicity patterns and to establish the dosage that produces maximum therapeutic effect with clinically tolerable toxicity. The drug was given by intravenous injection over 5-day courses repeated every 2--3 weeks. Toxic reactions included stomatitis, myelosuppression, skin rash, erythema, proctitis, and occasional nausea and vomiting. Stomatitis was the dose-limiting toxicity and it occurred in 32 patients. Myelosuppression was mild to moderate. Of 75 evaluable courses for marrow toxicity, leukopenia occurred in 14 and thrombocytopenia in 28. Thrombocytopenia was apparently dose-independet. Marrow recovery was complete by day 21 of therapy. Twelve patients developed mild or severe cutaneous toxicity depending on dose. When mild, the skin changes consisted of self-limited erythema or rash, and when severe, bullous lesions and skin ulcers were also observed. Proctitis occurred in six patients and was associated with severe stomatitis. Nausea and vomiting were occasional and mild. There was no evidence of liver or renal toxicity. All toxic manifestations other than marrow toxicity were dose-related. No responses were observed. A reasonable dose schedule is 45 mg/m2/day X 5 repeated every 3 weeks. We recommend that Phase II studies be pursued particularly in diseases that have been shown to be sensitive to the drug.


Carcinoma of the pinna.

Carcinoma of the pinna. Ninety-seven consecutive cases of carcinoma of the pinna are reviewed in this report. Fifty-six of the tumors were basal cell and thirty-nine squamous cell carcinoma. Fifty patients were surgically treated and forty-five irradiated. Small and/or peripheral lesions were excised and the large and/or centrally located lesions referred for irradiation. Analysis of the results shows no difference in tumor control rate, and the complication rate was also comparable with both modalities. Although chondritis was seen in three cases after irradiation, it also occurred in one case after excision. Our results indicate that neither modality should be used with total exclusion of the other. Initial resection would seem preferable in small lesions where primary closure is possible and in extensive lesions where a good cosmetic result is precluded by the destruction of normal tissue. Radiotherapy seems of value in those lesions in which resection would result in objectionable cosmetic defect.


Extended field radiation therapy in Hodgkin's disease: analysis of failures. A retrospective analysis of 116 primary cases of stage I, II and III-A Hodgkin's disease demonstrated 27 failures, fourteen confirmed by biopsy. Twenty of the 27 (74%) were in lymph node areas only and seven had extranodal extensions. The most frequent site of failure was the hilar nodes and contiguous lung. The majority of failures (78%) occurred within 30 months of treatment and the cause of failure determined in 23 (85%), sixteen of which were due to technical errors of irradiation. Analysis of the dosimetry in the mediastinal, hilar nodes and contiguous lung failures revealed three factors which may have contributed to a low dose. These factors are: 1) the equivalent square, 2) off-axis beam diminution, and 3) the anteroposterior dose profile. Combined radiation therapy and chemotherapy was more effective than either modality alone in the treatment of these failures.


Breast cancer following irradiation of the breast. During the period 1927--1957 1,115 women were treated at Radiumhemmet, Sweden with ionizing radiation for different non-neoplastic conditions of the breast. The average follow-up period was 31.5 years. The number of breast cancers occurring after irradiation was found to be four times the expected number and the breast cancer incidence rate in the irradiated breasts is dependent on the age of the patient at the first irradiation.


Intralymphatic BCG in the treatment of gynecologic malignancies: a phase I study. Thirteen patients with a variety of advanced gynecologic malignancies were administered BCG via the dorsal lymphatics of the lower extremity in addition to standard accepted forms of therapy. Prolonged febrile courses, lymphangitis and suppurative adenitis were observed along the lymphatic pathway of the injected lower limbs. There was no correlation between reaction to a standard anergy panel and survival. There was also no correlation between reaction to a standard anergy panel and the inflammatory response to intralymphatic BCG (ILP-BCG). There was, however, a positive correlation between the inflammatory response to ILP-BCG and survival. Intralymphatic administration of immunostimulants may conceivably be of value as ancillary therapy for use in gynecologic malignancy. However, complications of this approach to immunotherapy are significant and the method should not be used until complications are decreased.


Studies on carcinoembryonic antigen levels in patients with adenocarcinoma of the uterus. Carcinoembryonic antigen was determined before treatment in 101 patients with adenocarcinoma of the uterus. If 2.5 ng/ml is accepted as the upper normal value, 34% of the patients with cancer of the corpus had elevated levels. Only 7% had values exceeding 5 ng/ml. The highest recorded value in endometrial carcinoma was 8.5 ng/ml. In adenocarcinoma of the cervix 68% had values over 2.5 ng/ml and a direct correlation between nodal metastases and plasma elevation of CEA was found. The highest recorded value for endocervical cancer was 108 ng/ml. No patient with localized disease had a value over 4.0 ng/ml. It is concluded that adenocarcinomas of the cervix and corpus have different biological properties, and that in adenocarcinoma of the cervix determination of CEA is a reliable indicator of the extent of disease.


The reversible behavior of locally invasive endometrial carcinoma in a chromosomally mosaic (45,X/46,Xr(X)) young woman treated with Clomid. A 22 year-old phenotypic female with a 45,x/46,x, r(x) mosaic complement had anovulatory cycles, histologically normal ovaries, and atypical endometrial hyperplasia which, when clinically followed by repeated biopsies, was found to progress to locally invasive endometrial carcinoma. This was successfully managed by the induction of ovulation with Clomid, which resulted in conversion of the endometrium to a normal secretory pattern for two subsequent years.


Desmoplastic trichoepithelioma.

Desmoplastic trichoepithelioma. Fifty examples of a distinctive clinicopathologic entity occurred in 49 patients who ranged in age from 8 to 70 (median 46) years. Forty-nine tumors were on the face, mainly the cheek, chin and forehead; most were present one to five years, and 85% of the patients were female. The growths varied in size from 3 to 8 mm; many were hard and annular, with a raised border and depressed nonulcerated center. Histologically, narrow strands of basaloid cells and epidermoid cyts infiltrated a fibrotic stroma. This tumor, which we have named desmoplastic trichoepithelioma, must be differentiated histologically from morphealike basal cell carcinoma, desmoplastic cutaneous metastasis, and certain benign adnexal neoplasms.


Clear cell carcinoma of the ovary: light and electron microscopic studies. Twelve cases of ovarian clear cell carcinoma were studied histologically. Four cases were examined electron microscopically and compared with other conditions. Five tumors were directly connected with ovarian endometriosis. They were histologically classified into a tubular type with hobnail cells and a solid type without tubular pattern or hobnail cells. Electron microscopic figures of the tumor cells are identical having large nuclei, abundant glycogen, lamellated RER, few lipid droplets, and sparse but well-developed microvilli. The basophilic dark cells frequently encountered in the tubular type are morphologically quite similar to clear cells excepting for sparsity of glycogen and lipid droplets. Alveolar arrangement of 6 to 10 tubular structures (honeycomb structure) resembling alveolate structure seen in late secretory endometrium was found in tumor cells of one case. Ultrastructural feature of clear cell carcinoma closely resemble those of Arias-Stella endometrium and clear cell carcinoma of endocervix suggesting their Muellerian origin.


Extradural metastatic breast carcinoma detected on a bone scan. A patient with an untreated breast carcinoma and a clinically minimally symptomatic, extradural spinal cord compression secondary to metastatic disease is described. The observation of an abnormally distended urinary bladder on a bone scan led to the prompt diagnosis and successful treatment of a total spinal cord block.


Dysplasias of uterine cervix: epidemiological aspects: role of age at first coitus and use of oral contraceptives. Age at first coitus and use of oral contraceptives were studied in a highly homogeneous population (French Canadian) during a cytologic cervical cancer screening program. Both factors were known in 84,540 women without cervical lesions and in 2017 patients with mild and moderate dysplasia. Highly significant correlations were found between: early onset of sexual activity and occurrence of dysplasia; oral contraceptive use and occurrence of dysplasia; early age at first coitus and oral contraceptive use. When correlated for age at first coitus, there was a significant excess of dysplasias in oral contraceptive users. Dysplasia of the uterine cervix behaves epidemiologically like carcinoma in situ and invasive squamous carcinoma, that is, essentially as a venereal disease. It remains to be seen whether all dysplasias form one continuum or whether there are two morphologically similar but biologically distinct forms of dysplasia: one more frequent, regressing spontaneously, the other relatively rare, progressing to carcinoma in situ and invasive squamous carcinoma of the cervix.


A solitary functioning osseous metastasis from a malignant pheochromocytoma of the organ of Zuckerkandl. A case of a malignant phenochromocytoma of the organ of Zuckerkandl is reported. There was a solitary functional metastasis in the left femur, which was treated by hip disarticulation after removal of the primary. The patient is asymptomatic and free of further metastases after 3 years. Other reported cases of solitary metastases from malignant pheochromocytomas are cited. These occurred most frequently in the skeleton system, which is the most common site of distant metastases in malignant pheochromocytoma. The reported case and the review of the literature indicate that solitary or limited metastatic lesions should be treated surgically by partial or, when possible, complete resection.


Comparison of the classification by microscopic level (stage) of malignant melanoma by three independent groups of pathologists. The ability of groups of pathologists to classify and stage malignant melanoma varies with their familiarity with the new nomenclature proposed for that process. Primary lesions of malignant melanoma from 79 patients were independently examined and classified by community pathologists, university pathologists, and a referee pathologist all without access to each others diagnoses. The diagnoses of these groups were compared for agreement in variety of melanoma as well as depth of dermal penetration (stage or level). Greatest success (agreement with the referee) of both the community pathologists and the university pathologists was achieved when assessment of level of invasion (+/- 1) of the referee was compared (community pathologists = 94% +/- 12% agreement, university pathologists = 99% +/- 2% agreement). Our survey demonstrates that only a relatively small number of community pathologists (23%) employ the new nomenclature, but they do so with a facility equal to that of the university pathologists. Based upon this study and our continuing experiences, we recommend the review of all primary lesions of malignant melanoma by a pathologist or group experienced in the diagnosis and microscopic staging of the disease.


Epidemiologic and histologic patterns of Hodgkin's disease in blacks. The epidemiologic pattern for Hodgkin's disease in blacks from two different communities in the United States was characterized by higher childhood rates and significantly lower rates in the young adult and older age groups than for whites. In addition, a significantly greater number of black patients belonged to low occupational groups. These observations and the different epidemiologic patterns for blacks in Southern Transvaal, South Africa, and other countries suggest that the natural history of Hodgkin's disease might be strongly influenced by social milieu. The variability in Rye subtype distribution, particularly for whites and blacks in the young adult and other age groups raise the possibility that age related environmental factors might be important in the histologic reactivity of the host.


Systemic thermotherapy: description of a method and physiologic tolerance in clinical subjects. A safe, effective method of inducing total body hyperthermia to 42 degrees C (108 degrees F) has been developed and applied to clinical subjects with advanced malignancy. Physiological and biochemical parameters have been studied to determine tolerance and detect toxicity. Treatments were well tolerated with appropriate life support measures, mainly fluid and electrolyte replacement. Occasional arrhythmias and superficial cutaneous burns were the major complications. No evidence of central nervous system dysfunction was detected. Serum enzyme elevations after treatment appeared to indicate hepatic cellular injury but no clinical problems resulted. Renal, pulmonary, and hematologic parameters showed no significant changes from baseline values. Two early deaths occurred in patients with massive liver replacement with tumor and such patients may not be appropriate subjects for hyperthermia.


Benign blue nevus of the vagina.

Benign blue nevus of the vagina. Pigmented lesions of the vagina are very rare. A benign blue nevus of the vagina in a 73-year-old woman, diagnosed clinically as malignant melanoma, is presented. Although 15 cases of blue nevi of the uterine cervix have been reported, this is the first case of blue nevus located exclusively in the vagina.


A school screening program that works.

A school screening program that works. Between 1974 and 1976, school nurses in Montreal screened 26,947 children in grades seven and eight for adolescent idiopathic scoliosis. Of these, 4.6% had scoliosis positively diagnosed by radiographic examination; 4.5% were idiopathic in nature. The nurses were part of the Shriners School Scoliosis Program--a program that has proven to be a clinically sound, cost effective way of detecting early scoliosis, providing consistent follow-up and treatment and preventing progression of the condition. What follows is a description of how cooperation and planning among existing health institutions can make a preventive program work.


Epipodophyllotoxin VM-26 in the treatment of childhood neuroblastoma. Thirteen children with disseminated neuroblastoma that had become refractory to conventional chemotherapy were treated with the epipodophyllotoxin VM-26. Three patients developed partial responses (greater than 50% reductions in tumors and in the proportion of tumor cells in bone marrow). Acute nonhematologic toxicity after treatment was minimal. Hematologic toxicity was observed but could not be assessed accurately since most patients had abnormal hematopoiesis due to extensive tumor involvement of bone marrow. These results demonstrate that VM-26, as a single agent, can produce measurable tumor responses in children with neuroblastoma.


Implications of the 99mTc diphosphonate bone scan on treatment of primary breast cancer. The 99mTc diphosphonate scan is important in the study of primary breast cancer. The short-term prognosis for scan-positive patients is poor. Serial bone scans provide a safe and reliable prognostic index in patients following mastectomy. By correlating the scan with biochemical tumor markers, a matrix of diagnostic tests may be developed that is capable of identifying high-risk patients who may benefit from systemic therapy.


5-fluorouracil-induced increase of total serum thyroxine and triiodothyronine. Total serum thyroxine and triiodothyronine levels in a group of 15 patients with advanced mammary carcinoma significantly increased during weekly treatment with 5-fluorouracil, whereas serum free thyroxine levels and serum thyroid stimulating hormone levels were unchanged. No clinical signs of hyperthyroidism in these treated patients have been observed.


Differential distribution of antitumor agents in primary and secondary tumors. The differential distribution of a series of antineoplastic agents in metastatic tissues compared to their respective primary tumors has been investigated in one rat and two mouse experimental tumor systems, ie, the intramuscular Lewis lung carcinoma (3LL) of C57BL/6 mice, which gives rise to spontaneous lung metastases, the intratibial Sarcoma 180 (S180) of CD1 mice, which induces macroscopic metastases to the lymph nodes, and the Walker 256 carcinosarcoma of CD rats, which also metastasizes to the lymph nodes. The results described in this paper show that the concentrations of adriamycin, daunorubicin, cyclophosphamide and its alkylating metabolites, hydroxyurea, 1-methyl-1-nitrosourea, and 6-mercaptopurine are much higher in the pulmonary metastases of 3LL and/or in the lymph node metastases of S180 than the concentrations measured in the primary tumor. In the Walker 256 tumor system the distribution of adriamycin appears to follow the same pattern observed for the mouse tumors. Only for methotrexate (in the 3LL tumor) is the difference in the concentrations at the two sites not so evident. These findings are discussed in relation to the comparatively greater sensitivity of metastases to chemotherapy.


Tetrahydrouridine: Physiologic disposition and effect upon deamination of cytosine arabinoside in man. [14C]-tetrahydrouridine (THU), a strong inhibitor of cytidine (CR) deaminase, was, after iv administration, rapidly and quantitatively cleared from the blood with a plasma half-life of about 1 hour. The main pathway of excretion was through the kidneys: most of a dose of 50 mg/kg was excreted within 12 hours and excretion was essentially complete within 48 hours. Oral administration of the same dose revealed absorption of about 10% from the gastrointestinal tract. THU at 10, 25, and 50 mg/kg given 15 minutes before [3H]-cytosine arabinoside (ara-C) at a dose of 0.003 mg/kg produced about a two fold increase in ara-C blood levels at all times measured from 5 minutes to 4 hours, with only slight increases in the half-life of ara-C. A dose-related effect of THU upon the deamination of ara-C was obvious only during the time from 15 minutes to 1 hour after the injection of 3H-ara-C. The inhibitory effect of THU upon CR deaminase was also reflected in a considerably increased ratio of ara-C/uracil arabinoside in the urine.


Combinations of tetrahydrouridine and cytosine arabinoside in mouse tumors. Thirteen experimental mouse neoplasms were tested by cytidine (CR)-deaminase and deoxycytidine (dCR)-kinase levels. Four neoplasms, Sarcoma T241, Adenocarcinoma E0771, Lewis lung carcinoma (LL), and Sarcoma 180 Japan (S180J), considered to have high deaminase and sufficient dCR-kinase activities, were tested in vivo for combination chemotherapy with cytosine arabinoside (ara-C) and the CR-deaminase inhibitor, tetrahydrouridine (THU). THU did not significantly improve the growth inhibition of ara-C in a wide range of combinations in T241, E0771, LL, and the solid form of S180J, but more than doubled the survival time of the S180J ascites-bearing animals. Toxicity in the form of weight loss and toxic deaths was observed in some but not all groups, especially at high dosages of ara-C and THU. Tissue distribution of [3H]-ara-C and [14C]-THU in T241-bearing mice revealed an accelerated clearance of ara-C-derived radioactivity under the influence of THU in the tumor and five host tissues, but not in the small intestines. With the exception of the small intestines, clearance of THU-derived radioactivity was faster in all tissues studied compared to the clearance of [3H]-ara-C-derived radioactivity. Intracellular CR-deaminase levels were inhibited significantly, ie, dose dependent, in tumor and host kidney after a single ip injection of THU to E0771--bearing mice. In the solid S180J, with or without simultaneous ip administration of THU, [3H]-ara-C was not converted to 5'-di- and tri-phosphates at all. In mice bearing the ascites form of S180J, [3H]-ara-C was extensively converted to ara-C 5'-di- and tri-phosphates. THU increased both overall ara-C-derived radioactivity and the relative amounts of ara-C 5'-di- and tri-phosphates.


Adjuvant treatment with levamisole in cancer: a review of experimental and clinical data. Animal and human studies of adjuvant treatment with levamisole in cancer are reviewed and discussed. From the animal data it is concluded that the activity of levamisole is dose-dependent, more effective on slow-growing tumors, affects metastasis formation, preferentially is best when levamisole is used as an adjuvant to the usual cytoreductive treatments and that tumor enhancement is not expected. Clinical findings are put into perspective of the animal data and the most appropriate clinical situations are indicated.


Fibrinolysis and antifibrinolytic drugs in the growth and spread of tumours. In the last few years increased release of fibrinolytic enzymes from malignant cells has been observed, but the significance of this property in relation to malignant growth is still not fully understood. Antifibrinolytic drugs decrease the growth rate of some experimental tumours and might have a similar effect on human malignant tumours. Antifibrinolytic drugs might also decrease the intravascular shedding of tumour cells from primary tumours, but might on the other hand enhance the lodgement of those metastatic tumour cells already in the vascular bed of recipient organs.


Klebsiella serotype-13 capsular polysaccharide: primary structure and depolymerization by a bacteriophage-borne glycanase. Periodate oxidation and Smith degradation, methylation analysis including uronic acid degradation, partial hydrolysis with acid, bacteriophage degradation, and p.m.r. spectroscopy have been used to elucidate the primary structure of the Klebsiella serotype-13 capsular polysaccharide. The polymer consists of pentasaccharide repeating-units comprising a 4)-beta-D-Manp-(1 leads to 4)-alpha-D-Glcp-(1 leads to 3)-beta-D-Glcp-(1 leads to chain with a 3,4-O-(1-carboxyethylidene)-beta-D-Galp-(1 leads to 4)-alpha-D-GlcAp-(1 leads to branch at position 3 of the mannose. It is shown that there is a glycanase activity associated with particles of Klebsiella bacteriophage No. 13, which catalyses hydrolysis of chain beta-D-Glcp-(1 leads to 4)-beta-D-Manp linkages in the type-13 polysaccharide. The chemical basis of some serological cross-reactions of the Klebsiella K13 antigen is discussed.


The kinetocardiogram during the isoproterenol test for the assessment of coronary heart disease. 50 patients, 20 without heart disease and 30 with coronary heart disease (CHD), were studied by kinetocardiography (KCG), before and after administration of isoproterenol (initial dose 2 microgram/min, maximum dose 6 microgram/min). In the control subjects the KCG was unaffected by the drug. In contrast, in most of the patients with CHD isoproterenol induced the appearance or the increase of paradoxical systolic bulges, which are regarded as the expression of ventricular dyskinesia resulting from isoproterenol-induced transient regional ischemia. This test is recommended as a valuable noninvasive method for the diagnosis of ischemic ventricular dyskinesia.


Cardiac output monitoring during the acute phase of myocardial infarction: accuracy and precision of the thermodilution method. A triple human catheter was used for the determination of cardiac output during the acute phase of moycardial infarction in 23 patients. The correlation coefficient between thermodilution and the Fick method was 0.91. Precision of the method assessed by multiple repeated determinations was 4.8 or 5.6%. Quadruplicate determinations allowed to detect variations of cardiac output in the range of 0.465 1/min. Variation between two successive determinations of more than 9.4% can probably be attributed to a technical error.


Postural effects on the noninvasive baselines of ventricular performance. The effects of posture on time-based noninvasive measurements were determined utilizing the sequence supine-sitting-standing in a formal protocol in which observer biases were eliminated by blinding the measurement and calculation phases. Compared to the supine posture, the sitting and standing postures produced significant increases in heart rate, isovolumic contraction time, pre-ejection period and pre-ejection periog/left-ventricular ejection time and significant decreases in ejection time and ejection time index. The response patterns are consistent with their hemodynamic correlates cited in the literature which show increased adrenergic activity and decreased venous return in the sitting and standing postures, the effect on venous return being dominant.


Technetium-99m stannous pyrophosphate myocardial scintiphotos in patients admitted to rule out acute myocardial infarction. Technetium-99m stannous pyrophosphate (Tc-PYP) cardiac scintiphotos were performed on 101 of 221 patients admitted to the Coronary Care Unit to rule out acute myocardial infarction (AMI). Criteria were defined for the diagnosis of AMI, variant angina and unstable angina. 42 patients were diagnosed as having had an AMI. 22 patients had transmural and 20 patients had nontransmural AMI. 40 of the 42 patients with AMI (95%) had positive scintophotos; 2 (5%) had negative scintiphotos. 59 patients did not have an AMI; (97%) had negative scintiphotos. Four of these 59 patients had variant angina; all had negative scintiphotos. Seven of these 59 patients had unstable angina; 2 had positive scintiphotos. Tc-PYP scintiphotos have high sensitivity and specificity and are accurate in correctly classifying patients as having or not having AMI.


On the frequency of early systolic clicks in mitral valve prolapse. Phonocardiography was performed in 74 patients with mitral valve prolapse. 24 patients had early systolic clicks (less than 80 msec from S1). Four of them had associated systolic murmurs. 30 patients had mid or late systolic clicks (greater than 80 msec from S1). A systolic murmur followed the click in 13 of these patients. Both an early and mid/late systolic click were noted in three patients. 17 patients did not have systolic murmurs. Seven patients had 'silent' mitral valve prolapse. In summary, early systolic clicks are common  in mitral valve prolapse. In many instances the early click is not accompanied by a murmur. Echocardiography is recommended in patients with chest pain or arrhythmia of uncertain etiology, even if characteristic signs of mitral valve prolapse are absent.


The action of theophylline on potassium uptake in cardiac purkinje fibers. The effect of theophylline on potassium uptake of cardiac Purkinje fibers was studied under different conditions. The following results were obtained: (1) theophylline decreases K uptake and enhances Purkinje fiber automaticity; (2) norepinephrine and high [Ca]0 counteract the decrease in K uptake induced by theophylline; (3) adrenergic receptor blockers do not modify the effect of theophylline on K uptake; (4) norepinephrine increases K uptake and this effect is potentiated by theophylline and is little affected by imidazole and acetylcholine. It is concluded that theophylline may depress K uptake by releasing intracellular calcium and thereby inhibiting the sodium-potassium pump. However, theophylline potentiates the effect of norepinephrine on K uptake probably by enhancing the intracellular levels of cyclic AMP.


Simultaneous atrial and A-V junctional tachycardia. Three cases of simultaneous atrial and a-v junctional tachycardia, related to the administration of digitalis and occurring in a short period of 16 months, are reported. Severe myocardial damage, anoxia and shock may decrease markedly the tolerance of the myocardium to digitalis, and thus predispose to the occurrence of simultaneous atrial and a-v junctional tachycardia.


Prolapse of the mitral valve: clinical spectrum and coronary arterial distribution. Coronary angiograms were reviewed in 31 patients with idiopathic prolapse of the posterior mitral leaflet. There were 19 males and 12 females, ranging in age from 33 to 69. The coronary artery which supplied the posterior descending branch was designated as dominant. There were 27 dominant right coronary arteries and 4 dominant left coronary arteries. Attention was paid to whether the origin of the vessel which courses in the posterior atrioventricular groove branch was from the right coronary artery or the left circumflex. In the dominant right coronary artery group, the arterioventricular groove branch arose from the right coronary artery alone in 6 and from the left circumflex alone in 1 patient, and in 20 patients, from both. In the dominant left coronary artery group, the atrioventricular groove branch arose from the left coronary artery in all 4 patients. The frequency of dominant right coronary artery and left coronary and the origin of the atrioventricular groove branch did not differ in the patients with prolapse of the mitral valve from a control group of 30 patients similarly analyzed. In all instances, the atrioventricular groove branch arose from either the right coronary artery ro the left circumflex, or both. In no case was the arterioventricular groove branch totally absent. The results of this investigation do not support the thesis, previously advanced by others, that prolapse of the mitral valve is related to absence of the left circumflex coronary artery, but indicate a normal range of variation in coronary arterial distribution.


His bundle electrocardiography in the Wolff-Parkinson-syndrome. Evidence for combination of James and Mahaim conduction. His bundle electrographic studies with atrial pacing in 2 of 8 patients with the Wolff-Parkinson-White (WPW) syndrome demonstrated evidence for the combination of a James tract and Mahaim fibers. During normal sinus rhythm these 2 patients had P-H intervals of 65 and 75 msec and H-Q intervals of 15 and 35 msec, respectively. On atrial pacing, the P-H intervals showed a small increase with the H-Q intervals remaining constant. The QRS duration, delta-wave duration and P-J intervals remained relatively constant. These observations strikingly contrasted with the findings typical of Kenty-type conduction in the remaining 6 patients in whom during sinus rhythm, the His depolarization occurred simultaneously with the onset of the delta-wave on the surface ECG. During atrial pacing (ranges 85-174/min), in these 6 patients, there was a progressive increase in the duration of the delta-wave, gradual increase in the P-H and Q-H intervals, and an increase in the QRS duration. 5 of these 6 patients showed a progressive increase in the P-J intervals. These observations suggest a practival method for determining in the individual patient whether anomalous conduction is occurring via a Kent-type pathway or a combination of a James tract and Mahaim fibers arranged in series.


Evaluation of the exercise test in patients with angiographically documented coronary artery disease. 100 male patients with at least 75% obstruction of one or more coronary arteries were subjected to submaximal exercise tests. Among the 73 subjects who had positive tests, 92% of those with one-vessel obstruction had an ST depression of 1 mm, none having more than 2 mm; by contrast, 44% of those with three-vessel disease had an ST depression of more than 2 mm and only 27% on ST depression of 1 mm. Left-ventricular end-diastolic pressure exceeded 15 mm Hg in 86% of the patients who had an ST depression of more than 2 mm but only in 33% of those with a depression of 1 mm; impaired contractility was found in 81% of the former and in 36% of the latter. 92% of those with one-vessel obstruction were able to perform work of 75 and 100 W/min while only 25% of those with three-vessel disease were able to perform the same amount of work. The peak exercise heart rate and systolic blood pressure also decreased with the increase in the number of affected vessels.


Clinical and electrocardiographic correlations in pulmonary heart disease (cor pulmonale). It is now possible to diagnose early cor pulmonale by utilizing electrocardiographic fluctuations which are the result of moderate pulmonary hypertension and the accompanying effect upon right ventricular function. This holds whether the ECG alterations are produced by chronic obstructive pulmonary disease or by the rarer forms of obliterative lung disease. The late stage of cor pulmonale, in which right ventricular hypertrophy is manifest, should now be rarely encountered in view of our improved understanding of cor pulmonale and more rational therapeutic approaches to the underlying disorders.


XYZ electrocardiography: correlations with conventional 12 lead electrocardiogram. This brief describes (1) the significance of deflections recorded by the XYZ leads, (2) important diagnostic features of the XYZ leads in different normal and abnormal conditions, and (3) some of the discrepancies between the conventional 12 lead electrocardiogram and the XYZ leads.


Changes in phasic femoral artery flow induced by various stimuli: a study with percutaneous pulsed Doppler ultrasound. Transcutaneous blood flow measurements were performed by means of pulsed Doppler ultrasound flowmeter in the femoral artery of healthy subjects. The pulsatile flow pattern was changed characteristically from resting state by postocclusive reactive hyperaemia, by the application of amyl nitrite, xanthinol nicotinate, and angiotensin amide. During reactive hyperaemia systolic flow was increased, diastolic reverse flow was abolished, and the forward flow continued throughout diastole. Amyl nitrite augmented thenegative flow phase and reduced mean flow, while xanthinol nicotinate decreased the negative component and augmented mean flow. Angiotensin amide produced enhancement of the average flow by elevating systolic and diastolic flow equally over the base line. In each of these interventions the changes in flow were determined mainly by variations during the diastolic flow phase.


Electrophysiological changes in the canine atrium and ventricle during progressive hyperkalaemia: electrocardiographical correlates and the in vivo validation of in vitro predictions. The electrophysiological response to hyperkalaemia was reinvestigated in the whole dog for several reasons including: the paucity of comparative electrophysiological and electrocardiographical studies in which atrial and ventricular tissues were simultaneously investigated; the contrast between the clarity of findings in previous in vitro studies as compared with the rather conflicting results in earlier in vivo investigations; and the difficulty in validating the extrapolation from in vitro results and theory to the in vivo situation because of deficiences in the literature. Biphasic alterations in atrial and ventricular conduction times as well as excitability in response to progressively increasing hyperkalaemia were documented. The alterations in conduction times were reflected quite accurately by relevant electrocardiographical changes. Experiments in the whole animal were designed to test predictions based on membrane theory: the results offering strong support for the validity of extrapolating from the in vitro to the in vivo situation. The results of this study should help clarify and render interpretable many of the seemingly conflicting results in the literature.


Effects of isolated right and left ventricular stretch on regional arteriolar resistance. In order to evaluate right and left ventricular stretch receptors without concomitantly stimulating those of the contralateral ventricle, 12 dogs were placed on total cardiopulmonary bypass. Balloons connected to compliant reservoirs were introduced into the right and left ventricles. Changes in systemic, gracilis muscle, and paw perfusion pressure at a constant flow were used as indices of systemic, muscle, and cutaneous vascular resistance. To induce left ventricular stretch, the balloon in that chanber was rapidly inflated from a mean pressure of 1.33 kPa (10 mmHg) to a mean pressure of 7.32 kPa (55 mmHg) for 15s (6.00 kPa [45mmHg] increment). For right ventricular stretch, the pressure was increased from 0.67 to 4.00 kPa (5 to 30 mmHg) for 30 s (3.34 kPa [25 mmHg] increment). Both left and right ventricular stretch produced a significant fall in systemic (-4.92 kPa [-37 mmHg], -36%) and gracilis muscle (-5.59 kPa [-42 mmHg], -30%) perfusion pressure, with only minimal changes in cutaneous vascular resistance (-0.80 kPa [-6 mmHg], -4%). This reflex was found to be vagally mediated, to have a low threshold for stimulation (left ventricle, 0.67 kPa [5 mmHg] increment; right ventricle, 1.33 kPa [10 mmHg] increment), and to have a neurogenic sympathetic alpha-adrenergic efferent limb. The low threshold for stimulation suggests that these reflexes may play a physiological role with changes in body position and may be important in such pathological conditions as semilunar valvular stenosis and myocardial infarction.


An autoperfusion technique for nonsteady-state vascular pressure-flow analysis in the rat. A technique was developed to measure pressure-flow relationships in the autoperfused intact subclavian vascular bed of areflexic rats. Changes in blood flow and perfusion pressure were produced by occlusion of the aortic arch. This perfusion technique is suitable for evaluating vascular distensibility and responsiveness in the rat.


Reversal of aconitine-induced tachycardia by prostaglandins in the rabbit Langendorff preparation. The ability of PGA2, E1, E2, and F2alpha to alter: (a) the refractory period (as judged by the maximal driving frequency); (b) the rate of automatically beating aconitine-treated papillary muscles; and (c) the rate of both untreated and aconitine-treated Langendorff preparations, was studied. The addition of PGA2 (3.0 mumol), PGE2 (2.84 mumol), and PGF2alpha (2.1 mumol) to the perfusate returned heart rate to pre-aconitine levels in the Langendorff preparation, but this action was frequently accompanied by atrioventricular dissociation. In contrast, PGE1 (2.82 mumol) was ineffective in antagonising aconitine-induced tachycardia. In the normally beating rabbit Langendorff, PGF2alpha (2.1 mumol) produced a slight but statistically significant negative chronotropic effect. Neither cardiac contractile force nor maximal driving frequency was altered by the addition of prostaglandins. These results suggest that PGA2, PGE2, and especially PGF2alpha may exert antiarrhythmic activity by direct action(s) upon in vitro rabbit myocardial preparations.


Diagnosis of valvular heart disease using transcutaneous Doppler ultrasound. An ultrasonic Doppler instrument capable of measuring mean and maximum velocities inside a small sample volume is presented. The instrument has been used for determining velocities in normal and diseased heart valves. A method is described for identifying the different heart valves, based on their relation to one another as well as the form of the velocity curve. The pressure drop across the mitral valve can be determined from the maximum velocity and the mean velocity can be used to determine the degree of aortic insufficiency. Recordings of mean and maximum velocities can give an indication of the form of the whole spectrum, thus making complete frequency analysis unnecessary for most purposes.


A method of left ventricular ejection fraction estimation from cineangiocardiograms employing a special-purpose calculator. A special-purpose calculator is described which computes the left ventricular ejection fraction and end-diastolic volume (and thus stroke and end-systolic volumes) from single-plane cineangiocardiograms. A pair of manual callipers is used to convert the length information of angiographic projections into digital form for processing by the calculator. Volumes are estimated by means of a first order numerical integration method assuming circular cross-section. The angiograms of 42 patients were analysed using both the calculator and a conventional method. The results of the 2 methods correlated very closely (r = 0.99) with a slope within 1% of unity. The calculator is suggested as a practical and cheaper alternative to computer-based systems.


Innervation of heart and alary muscles in Sphinx ligustri L. (Lepidoptera). A scanning and transmission electron microscopic study. The origin and orientation of the heart nerves in Sphinx ligustri and Ephestia kuehniella were investigated by scanning electron microscopy using a special technique which involved pinning the dissected specimens on a stabilizing metal pad. The heart and alary muscles in Sphinx particularly their caudal extremity were also examined by transmission electron microscopy. The alary muscles form an incomplete sheath around the heart with a mainly longitudinal fibre orientation, e.i. antagonistically to the fibres of the heart itself. The heart and alary muscles are multiterminally innervated by branches of the transverse segmental nerves. All branches contain a single electron lucent axon; the thickest branches also possess several neurosecretory axons. Swellings of the segmental nerves may indicate the position of nerve cell bodies. There are no lateral heart nerves. Only one type of neuromuscular junction is abundant in the alary muscles but less frequently found in the heart. The terminals originate from the central axon only. They are capped by glial cells, which interdigitate with the muscle cells. They penetrate into the T-system toward the Z-discs and form a complex intercellular space system. Exocytosis of dense-cored vesicles into this "perisynaptic reticulum" seems likely. Sites of neurohaemal release are distributed along the nerve branches and special nerve endings occur at the level of the ostia. The possible nervous influence upon heart activity is discussed.


Ultrastructural observations suggesting merocrine secretion in the initial segment of the mammalian epididymis. Principal cells in the initial segment of the epididymis in horses, cattle, pigs, sheep, dogs, cats, and rabbits have an abundant, partly rough, endoplasmic reticulum and a large Golgi complex. Small vacuoles with opaque content seem to be formed by the Golgi complex and move to the cell apex, where they empty their contents into the lumen by a merocrine mechanism.


Circadian rhythm in the number of granulated vesicles in the pinealocytes of mice. Effects of sympathectomy and melatonin treatment. Adult, Charles River CD-1, male mice were housed in an environmental control chamber under strict conditions of controlled light (12D/12L) and temperature. The mice were sacrificed at various times throughout the twenty-four hour clock and their pineals prepared routinely for electron microscopy. The number of dense-cored or granulated vesicles present in the polar terminals of pinealocytes were quantitated in thin cross sections through pericapillary areas. A distinct circadian rhythm was observed in the number of granulated vesicles with a three- to four-fold difference between late photoperiod maximum and late dark period minimum. The rhythm was abolished by bilateral superior cervical ganglionectomy. These results are consistent with the hypothesis that the granulated vesicles are synthesized and stored in the pinealocytic cytoplasm during the photoperiod under the tropic influence of norepinephrine, and are released during the dark period when melatonin synthesis is greatest. Melatonin, administered as daily intraperitoneal doses of 50 microgram over a period of five days, was observed to increase markedly the number of pinealocytic granulated vesicles during the light period, but led during the dark period to a decrease in their numbers to levels below that of diluent-treated controls. It may be that melatonin stimulates the synthesis and/or release of granulated vesicles which represent the packaged form of a major secretory product.


The structure and differentiation of granulated metrial gland cells of the pregnant mouse uterus. A study was made with the light and electron microscopes of the granulated metrial gland cells of the decidua basalis of the pregnant mouse uterus, up to day 11 of pregnancy. The granulated metrial gland cells are large, up to 50 mu in diameter, mono- or binucleate and the glycogen rich cytoplasm typically contains many large glycoprotein granules which may be up to 5 mu in diameter. Morphological evidence is described in support of a lymphocyte-like cell being the precursor to the granulated metrial gland cell. This differentiation sequence is similar to that already proposed in the rat but differences between the ultrastructure of the mature metrial gland cells of rats and mice were noted.


Observations on the gastric epithelium of ascidians with special reference to Styela clava. Transmission electron microscopy shows the gastric epithelium of Styela clava to comprise at least three distinct cell types. Ciliated mucous cells which form the crest of each stomach ridge produce mucus by an unexpected route. Vacuolated cells lining the ridge sides appear to be absorptive in function. Gastric enzymes are produced by typical protein secreting cells scattered amongst the vacuolated cells. Undifferentiated cells are found in the crypts between ridges. The structure and function of the gastric epithelium in Styela is discussed with special reference to the wider concepts of ascidian gut organization.


Fine structure and peroxidatic activity of rat blood monocytes. Rat blood monocytes contain granules of two types, primary and secondary granules, which can be distinguished on morphological grounds. Secondary granules have a halo between the limiting membrane and the matrix; primary granules have no halo and are generally more elongate than the secondary granules. In addition, there are differences in the distribution of the diameters of these two types of granules. The cytochemical characteristics of the peroxidatic activity of these granules were investigated by using different prefixation conditions in combination with a number of DAB media differing in pH and H2O2 concentration. Prolongation of the prefixation and increasing the pH of the incubation medium increased the staining intensity of the secondary granules and decreased the staining intensity of the primary granules. In unfixed cells peroxidatic activity could be demonstrated only in the primary granules. It is concluded from the present findings that peroxidase occurs in primary granules and not in secondary granules, whereas catalase is present in secondary granules but probably not in primary granules. No evidence was found for the presence of microperoxisomes in rat blood monocytes.


Further observations of transport within paddle cilia. Rhabdopleura has densely ciliated tentacles and cephalic shield. These cilia are of two sorts, ordinary cilia and those bearing paddle-like swellings. These swellings, about 1 micron across, are in the ciliary membrane. The axoneme bundle within the cilium remains intact, keeping the usual spatial arrangements, except that in the swelling its overall diameter is reduced. It is suggested that the mechanism for moving the paddle-like swellings along the length of the cilium is the releasing and reattaching of the side filaments from the axoneme to the ciliary membrane.


Quantitative ultrastructural evidence of alterations in prolactin secretion related to external salinity in a teleost fish (Poecilia latipinna). Quantitative ultrastructural morphometric studies were made on the prolactin cells of Poecilia latipinna adapted to freshwater (FW), one-third seawater (1/3 SW) and full-strength seawater (SW), and at various times after transfers between 1/3 SW and FW. In fully-adapted fish the rates of prolactin (PRL) synthesis and PRL release are inversely related to environmental salinity. During adaptation to a new salinity the two rates are temporarily uncoordinated, with release increasing or decreasing more readily than synthesis. Synthesis appears to take 30 h or longer to come into balance with the increased release rate following transfer from 1/3 SW to FW, and 72 h or longer to adjust to the reduction in release rate that follows the reverse transfer. The excess PRL granules that accumulate in the latter situation appear to be removed by lysosomal digestion. As in other teleosts, in fish adapted to the external medium the size of the stored PRL granules is inversely related to external salinity, but this relationship breaks down during adaptation to a new salinity. The stellate cells which penetrate between the PRL cells are more prominent, more extensively ramified, and appear more metabolically active in FW-adapted fish than in the other groups. These cells seem to be closely related in function to the secretory activity of the PRL cells.


Cytochemical study of the lamellar bodies in the swimbladder of the toadfish Opsanus tau L. The columnar epithelial cells of the gas gland in the swimbladder of the toadfish, Opsanus tau L., contain lamellar bodies that resemble the lamellar bodies found in epithelial cells of vertebrate lungs. Cytochemical assays indicate that swimbladder lamellar bodies are soluble in chloroform-methanol solution, react with tricomplex flocculation solution (indicating a phospholipid component), exhibit a positive reaction for cholesterol when exposed to digitonin, and contain acid phosphatase. The anterior chamber of the toadfish swimbladder is lined by an extracellular layer. Digitonin-cholesterol crystals are found in this layer when the swimbladder is treated with digitonin. A ruthenium red positive layer is also present in the anterior chamber of the toadfish swimbladder. The structure and cytochemistry of swimbladder lamellar bodies are compared with those of vertebrate lung lamellar bodies. Similarities between the extracellular layer in the swimbladder and the extracellular layer in lungs are also noted.


The subcellular distribution of zinc in dog prostate studied by x-ray microanalysis. X-ray microanalysis of zinc in ultrathin sections of dog prostate was performed by electron microscope microanalysis using the potassium pyroantimonate method of preparation. Prostates of both mature and immature dogs were examined and the metal was found to be localised primarily in the nucleolus, nuclear chromatin and secretory granules of epithelial cells. Differences in zinc concentrations were observed between mature and immature tissues, particularly in the nuclear chromatin. The metal was also incorporated into epithelial secretions, lysosomes and fibromuscular stroma. Variable binding of zinc to tissue components was revealed by a combination of histochemical precipitation and subcellular analysis.


Liposolubility as an aspect of nitrosamine carcinogenicity: quantitative correlations and qualitative observations. Carcinogenicity data for a number of nitrosamines have been examined for possible structure-activity correlations with liposolubility by the method of Hansch. Correlations were found in two cases which support a previous mechanistic suggestion and which also suggest a possible difference between the action of nitrosopiperidines and dinitrosopiperazines in inducing olfactory carcinomas. No correlations were found for non-cyclic nitrosamines.


Sex- and strain-dependent hepatic microsomal ethylmorphine N-demethylation in mice: the roles of type I binding and NADPH-cytochrome P-450 reductase. The roles of type I binding and NADPH-cytochrome P-450 reductase in ethylmorphine demethylation were investigated in two strains of mice, using sex differences in these activities as a tool. In the CPB-SE strain, females metabolize ethylmorphine faster than males. Sex differences in cytochrome P-450 content and endogenous NADPH-cytochrome P-450 reductase activity were too small to account for this. On the other hand, the differences in the magnitudes of type I spectra and ethylmorphine-induced enhancement of cytochrome P-450 reduction were considerable larger than those in the rates of demethylation. All parameters, except endogenous cytochrome P-450 reduction, were modified in a similar way by testosterone pretreatment: in females they were depressed to the male level, whereas in males they remained unchanged. Castration had no effect in females and enhanced the activities in males. The CPB-V strain exhibited little or no sex differences in ethylmorphine demethylation, cytochrome P-450 content and endogenous cytochrome P-450 reduction. Testosterone pretreatment had little or no influence on these activities. Type I binding and reductase stimulation, however, showed sex differences, comparable to those observed in the CPB-SE strain, which were also abolished by testosterone. A relationship between reductase stimulation and type I binding was observed, which was, apparently, independent of sex or strain. It is concluded that androgen primarily influences the amount of cytochrome P-450-substrate complex formed, but that the reduction of this complex is not rate-limiting in the demethylation of ethylmorphine.


[Mutagenicity of dichloroacetaldehyde and 2,2-dichloro-1,1-dihydroxy-ethanephosphonic acid methyl ester, possible metabolites of the organophosphate pesticide Trichlorphon]. Dichloroacetaldehyde and 2,2-dichloro-1,1-dihydroxy-ethanephosphonic acid methyl ester which are formed solvolytically from desmethyltrichlorphone, an in vivo metabolite of the organophosphorus pesticide Trichlorphone, show in the dominant lethal test in mice at equimolar dosage (1.6 mmol/kg) a mutagenic activity comparable with that of Trichlorphon. Therefore it cannot be ruled out that the genetic effects of this pesticide may be due in part to the action of its degradation products.


Study of prolonged hyposensitization with D. pteronyssinus extract in allergic rhinitis. Sixty-six Chinese patients with rhinitis, with or without asthma, were randomly allocated to a course of injections either with E. pteronyssi-us extract or placebo. The course consisted of 18--22 weekly injections, followed by monthly maintenance injections with the highest concentration for 1 year. Progress was evaluated by a patient's daily diary and monthly assessments by the physician, by comparisons of skin and nasal challenge tests and by the specific serum IgE concentration, before treatment, at the end of the weekly course, and once during the maintenance course. No improvement was detected at the end of the weekly course, but during maintenance there was a consistent benefit to the patients receiving the D. pteronyssinus extract both in the diary and the physician's assessment, especially the former. There was no consistent change in the skin or nasal challenge tests and there was a trivial fall in the serum IgE levels in the patients on the extract. Adverse reactions were much more common in the patients on the extract, but most were trivial. The different methods of assessment used and the role of hyposensitization with D. pteronyssinus are discussed.


Correlation between skin tests, inhalation tests and specific IgE in a study of 120 subjects allergic to house dust and Dermatophagoïdes pteronyssinus. The radioallergosorbent test was compared with currently accepted allergy diagnostic techniques in seventy-four controls and 120 patients with a clinical history of allergy to house dust and Dermatophagoïdes pteronyssinus. The results obtained with D. pteronyssinus allergen extract show a close correlation between the size of the cutaneous reactions and the serum level of allegen-specific IgE. On the other hand, highly positive skin tests to house dust were not always correlated with a positive RAST response for house dust. Similar results were found with inhalation tests. When a purified D. pteronyssinus extract was used, a stronger relationship was observed between RAST, cutaneous and inhalation tests. It can be assumed that RAST for house dust is not of value in patients with house dust and mite allergy. Our findings indicate that the correlations between RAST results and other in vivo test results depend on the purity of the allergen extracts and the selection of patients.


Delayed asthmatic response to inhalant allergen: cantharidine beetle, case report. A case history of an asthmatic patient who developed delayed responses to intradermal and inhalation provocation tests with whole body allergen of a common beetle (cantharidine) is presented. The response was maximal at 48 hr after the test and it took almost a week for complete resolution. Prior administration of sodium cromoglycate failed to inhibit this response, whereas corticosteroid treatment completely inhibited it. An asthmatic response which appears 48 h after inhalation challenge with an insect allergen is a new variety and the mechanism needs study.


The variability of skin test hypersensitivity reactions in cystic fibrosis and asthma. Cystic fibrosis (CF) children had a greater variability of skin prick test response compared with asthmatic children, when the tests were performed on two occasions. This suggests that there is a different cause for the allergy in the two groups, perhaps because the asthmatics have a transient period of susceptibility to sensitization in infancy and the CF children a persistent vulnerability. Amongst the asthmatic children, clinical improvement was associated with loss of some skin prick test reactions, and clinical deterioration with an increase in the number of positive reactions. Thus continuing allergic reactions may maintain a mucosal defect, resulting in a persistence of susceptibility to allergen sensitization, and control of the reactions may re-establish normal mucosal defence mechanisms.


Grass pollen content of the air in the Bristol Channel region in 1976. The grass pollen content of the air at four sites bordering the Bristol Channel (at Bristol, Cardiff, Penarth and Penmaen) was studied. The trap at Penmaen was situated at an official climatological station which provided the meteorological data used in the surveys. Although at certain times large differences could be seen between the concentrations of grass pollen at the different sites, overall the findings for the four sites were similar. Changes in the atmospheric pollen concentration related to variations in meteorological conditions. At the peak of the season high concentrations of grass pollen persisted throughout the night.


Familial human short-term sensitizing (IgG S-TS) antibody. Skin tests on a middle-aged English housewife (the initial case) with a history of seasonal grass pollen rhinitis and asthma showed strong immediate and late reactions to grass pollens. Early in the grass pollen season, 1976, RAST showed normal levels of IgE antibodies in the serum. Passive transfer in Rhesus monkey skin was also negative for heat-labile IgE but gave a very vigorous reaction for short-term sensitizing heat-stable IgG antibody (IgG S-TS Ab). Skin tests and studies on sera from other members of the family showed that another five also formed IgG S-TS Ab, and indicated that the ability to form this antibody was familial. One member of the family had only an immediate reaction on skin testing, and much IgE to grass pollen. Towards the end of the grass pollen season the IgE titre in the initial case had been tripled and the IgG S-TS Ab had disappeared. By September the specific IgE titre had risen even further.


A dietary free from additives in the management of allergic disease. Some patients who suffer from asthma, rhinitis or urticaria undergo exacerbation of symptoms following ingestion of foods or beverages containing azo dyes, sulphur dioxide or benzoates, which are used as preservatives. These patients may be mistakenly thought to be suffering from specific food allergies. A dietary is presented which is free from these additives. Drugs and their coatings and capsules may also contain azo dyes and these should be avoided by patients on an additive-free diet. Four cases are reported illustrating recovery, one from asthma and three from chronic urticaria after commencing this diet.


Allergic drug reactions: an in vitro model using a mixed function oxidase complex to demonstrate antibodies with specificity for a practolol metabolite. Reactive metabolite products of the drug practolol were generated in vitro using the rat liver mixed function oxidase complex. The metabolites were spontaneously coupled to a non-agglutinating rabbit antibody to human O red blood cells, so forming a metabolite-antibody reagent. This reagent was then used to passively sensitize human O red cells which subsequently acted as indicator cells for detecting anti-metabolite antibodies.


Selective isolation of allergens. I. Reaction of house dust mite extracts with tridacnin and concanavalin A and examination of the allergenicity of the isolated components. Tridacnin, a lectin from the clam Tridacna maxima was found to precipitate with crude extracts from the house dust mites Dermatophagoides farinae and Dermatophagoides pteronyssinus. Using tridacnin in direct precipitation and affinity chromatography studies, a carbohydrate-rich preparation of high molecular weight was isolated from D. farinae extracts. The isolated preparation gave one precipitin line when used with tridacnin in gel diffusion and immunoelectrophoresis experiments but two bands were seen on polyacrylamide disc gels after electrophoresis at pH 8.9. Radioallergosorbent test (RAST) studies demonstrated that the isolated material reacted strongly with sera from human subjects allergic to house dust mites and accounted for a significant proportion of the IgE binding capacity of the crude D. farinae extracts. Only one out of fifteen mite-allergic subjects gave a positive response when prick tested with the isolated preparation at a concentration of 0.2 mg/ml. A possible explanation for the discrepancy observed between RAST and skin test results is discussed. Concanavalin A also precipitated with D. farinae extracts but the material isolated with this lectin did not react with tridacnin and reacted weakly in the RAST with sera from mite-allergic subjects. We suggest that the high molecular weight component(s) which react with tridacnin may be useful for immunotherapy of house dust mite allergy.


IgE, parasites and asthma in Tanzanian children. Two rural Tanzanian primary schools were surveyed to test the hypothesis that parasitic infestation prevents the development of asthma. 242 pupils were interviewed to determine the prevalence of pupils with recurrent episodes of wheezing. The nineteen pupils so discovered had more exercise-induced bronchial lability than equivalently exercised controls. More girls (12.8%) than boys (3.3%) had asthma. In one school, 77% of the controls had faecal parasites, mainly Ascaris spp., and in the other school 55% of the controls had Schistosoma haematobium in their urine. Parasites were found in similar proportions in the asthmatics. The mean serum IgE for the whole population was 3174 u/ml with no demonstrable difference between the asthmatics and controls. There was no difference in immediate cutaneous hypersensitivity to twenty-two allergens between the asthmatics and controls. These findings suggest that parasitic infestation does not prevent the development of asthma.


Predictive value of serum IgE levels during rush hyposensitization. Thirty children with hay fever were studied with in vivo and in vitro tests during rush hyposensitization with Timothy pollen. Clinical assessment was made with the aid of diaries during one season before, and three seasons after, the start of the immunotherapy. When the serum level of IgE increased more than 10% during the first week of the therapy, symptoms were mostly alleviated during the following seasons. An alleviation was rarely found in children with decreasing or unchanged serum IgE levels. No predictive information as to the clinical effect of the immunotherapy was obtained from skin or provocation tests, nor from Timothy-specific antibodies of the IgG or IgE classes. It is proposed that serum IgE determinations should be performed before, and 1 week after, the start of rush hyposensitization in order to find probable therapeutic failures.


Immunoglobulin E specific to wheat and rye flour proteins. We have used the radioallergosorbent test (RAST) to determine IgE antibodies specific to wheat flour proteins in the sera of seven groups of patients. In some cases rye-specific IgE was also determined. Wheat and rye RAST scores showed a good correlation, presumably due to cross-reactions. Among bakers with asthma, positive scores, 0.5-3, occurred with a prevalence of 43%, and among children with eczema, scores in the range 0.5-4 were found with a prevalence of 54%. A score of 0.5 was a marginal value which was also occasionally encountered with sera from patient groups with no history of immediate hypersensitivity to wheat or rye. These groups included adults and children with allergic rhinitis and asthma, children from the general population and children with coeliac disease. The RAST appeared useful in the diagnosis of allergy to inhaled flour dust among bakers. Among children with eczema, positive wheat and rye RAST results were a common finding, which only occasionally could be linked to strong and unequivocal reactions to the foods in question. Both in bakers and children with eczema, wheat and rye RAST results showed good agreement with intracutaneous skin test results.


Haemostatic and complement changes in a family with 'allergic' disorders. A family with allergic manifestations, haemostatic disturbances, total absence of haemolytic activity of the complement system and low IgG levels is described. It is suggested that this functional abnormality of the complement system and the decreased level of immunoglobulin G may be due to immune complex reactions.


Allergen-induced increase in non-allergic bronchial reactivity. Non-allergic bronchial hyper-reactivity is a feature of most patients with asthma. We have measured non-allergic bronchial reactivity to inhaled histamine and methacholine in thirteen asthmatic subjects before and after allergen inhalation in the laboratory. The allergen inhalation produced mild early asthmatic responses (19-40% FEV1 fall) in all thirteen, additional definite late asthmatic responses (17-29% FEV1 fall) in four, and equivocal late asthmatic responses (5-11% FEV1 fall) in five. Following allergen inhalation, non-allergic bronchial reactivity increased in seven for up to 7 days. The seven included all four with definite late asthmatic responses and three of the five with equivocal late asthmatic responses. We conclude that allergens make asthma worse, partly through non-allergic mechanisms, and that avoidance of allergens is important in reducing non-allergic bronchial hyper-reactivity.


Fungal antigens as a source of sensitization and respiratory disease in Scottish maltworkers. Mycological and serological studies were carried out as part of a survey of respiratory disease in Scottish maltworkers. 70% of stained sputum smears from 574 workers showed the presence of higher plant cells and/or myclelia, and the spores of common environmental fungi. Penicillium spp. (90%), Rhizopus stolonifer (48%) and yeasts (53%) were the dominant fungi in 699 sputum cultures, and showed a similar proportional distribution in 327 samples of grain, malt, culms and dusts from fifty-six maltings. 57% of 711 men were serologically positive for fungi, 22% for Aspergillus fumigatus, 20% for A. clavatus, 10% for A. niger, 16% for Cladosporium herbarum and over 3% for Rhizopus stolonifer, 6% of 132 men were positive for Penicillium cyclopium. No precipitating antibodies to antigens from Alternaria tenuis, Aureobasidium pullulans, Candida albicans, Geotrichum candidum, Rhodotorula glutinis or Trichoderma viride were detected in tests of forty sera. Sera from the 5.2% of men with symptoms of extrinsic allergic alveolitis showed increased reactivity to mycelial antigens from Aspergillus clavatus. The fungus was cultured from 21% of maltings, 7% of all environmental samples and from the sputa of 8% of maltworkers.


Comparison of salbutamol Rotahaler with conventional pressurized aerosol. Salbutamol in a powder aerosol from the Rotahaler insufflator was compared, with equal doses of the conventional pressurized aerosol by dose-response curves and in a 1 month open trial, in the treatment of asthma patients with good inhalation technique. Results were not significantly different in either study. A further group of asthma patients, who were known to be incapable of using pressurized aerosols effectively, were shown to benefit from treatment with the Rotahaler. This device should increase the value of the sympathomimetic drugs to the minority of asthma patients who cannot use conventional aerosols correctly.


Unusual pattern of metabolites in the urine of child with tyrosinemia: glyceraldehyde. An unusual metabolite has been found in the acidic fraction of the urine of a child with tyrosinemia. This compound has been identified as glyceraldehyde, in addition to phenylacetic acid and p-hydroxybenzaldehyde, on the basis of gas chromatograph-mass spectral data and comparison with authentic samples.


A simple colorimetric method for determination of serum triglycerides with lipoprotein lipase and glycerol dehydrogenase. A simplified enzymic procedure to determine accurately serum triglycerides is described. Serum triglycerides are hydrolyzed completely to free fatty acids and glycerol by lipoprotein lipase from Pseudomonas fluorescens. The released glycerol is oxidized with glycerol dehydrogenase from Erwinia aroideae in the presence of NAD+, were the reduction of the enzyme-linked NAD+ is coupled to the reduction of nitro blue tetrazolium as a chromogenic indicator with phenazine methosulfate serving as an intermediate electron carrier of NADH. The absorbance at 570 nm is measured. The method requies only 20 microliter of serum and a 10-min incubation and is rapid and simple. The present method offers the measurement of a high concentration of triglyceride up to 1000 mg/dl serum. The results obtained by the present method show good correlation with those obtained by the glycerol kinase method (correlation coefficient, 0.989) or the acetylacetone method (correlation coefficient, 0.979). These results suggest that the proposed method will be utilized as a method or routine clinical test.


Determination of red blood cell superoxide dismutase and glutathione peroxidase in newborns in relation to neonatal hemolysis. Superoxide dismutase and glutathione peroxidase activities have been determined in newborns. Their mean values are approximately the same as in normal adults. In some cases a low content of superoxide dismutase and/or a high (superoxide dismutase/glutathione peroxidase) ratio are associated with hematological symptoms. In addition, a low superoxide dismutase activity is associated with hyperbilirubinemia and is present in two of the three cases showing maximal acetylphenylhdrazine-induced hemoloysis.


Enzyme thermistor determination of glucose in serum using immobilized glucose oxidase. An enzyme thermistor assay for serum glucose is described. The glucose present in the sample is reacted in a small column containing glucose oxidase immobilized to controlled pore glass (single thermistor device). The heat produced in the primary reaction is measured directly in the column without any need for coupling reactions. The useful linear range is 0.01-0.45 mM glucose, permitting 50-fold dilution of serum samples. Advantages are low enzyme cost, due to the immobilization, insensitivity for the color or any turbidity of the sample, and no requirement for coenzyme or any ancillary reaction. Improved sensitivity and extended linear range (0.01--0.9 mM) can be attained through a secondary reaction using catalase. The application to glucose analysis of a split-flow enzyme thermistor equipped with a reference column to eliminate unspecific heat effects is also described. The enzyme thermistor determinations were also compared with a spectrophotometric continuous flow technique using a small column with immobilized glucose oxidase and 4-aminoantipyrine and phenol as color reagents.


[Determination of lecithin-cholesterol acyltransferase. Studies on the precipitation of beta-lipoproteins by dextran sulphate (author's transl)]. Uncertainties in assays of lecithin-cholesterol acyltransferase (LCAT) are generally related to the degree of isotopic equilibrium obtained by rapid exchange of unesterified cholesterol between the different lipoproteins. A new method is presented based on the precipitation of serum beta-lipoprotein with sulfated polysaccharides prior to the LCAT determination. In the absence of Beta-lipoproteins, more than 7 per cent of serum free cholesterol is esterified in the first hour and the reaction rate is linear for about 2 h. LCAT activities with normal serum expressed as cholesterol esterified per microliter mol/1/h are lower than the values reported by others. The reason for this discrepancy is that free cholesterol specific activity in total serum does not reflect the true specific activity of LCAT cholesterol substrate.


A gas chromatographic-mass spectrometric (GC-MS) assay for 3-methoxy-4-hydroxyphenethyleneglycol and vanilmandelic acid in human serum. Procedure for the quantification of 3-methoxy-4-hydroxyphenethyleneglycol (MHPG) and vanilmandelic acid (VMA) in human serum are described. MHPG was selectively acetylated then determined as its 4-acetyl-di-trifluoroacetyl derivative and VMA as its di-pentabluoropropionyl-methyl ester. Deuterium-labeled MHPG and VMA were used as internal standards. Each of these metabolities and the resprective internal standards was recorded by double ion monitoring respectively, and the ratios were determined for specificity. Assay sensitivities of 1.0 ng/ml for MHPG and 2.0 ng/ml for VMA were achieved using 0.5 ml of serum. Total and free MHPG concentrations in human serum were determined to be 16.5 ng/ml +/- 4.4 (S.D.) and 4.6 ng/ml +/- 1.0 respectively from 10 normal male subjects. Free VMA concentrations were 7.0 ng/ml +/- 1.5; thus the ratio of MHPG/VMA was calculated to be 2.4 +/- 0.7 in these subjects. Of these two major normal metabolites of norepinephrine, MHPG is regarded to be largely derived from the central nervous system while VMA is from the periphery. The procedures are highly specific as well as simple and sensitive enough to permit simultaneous measurement of these two metabolites in a series of multiple samples from an individual.


Assay of ornithine carbamoyltransferase activity in human liver using carbon-labeled ornithine and thin-layer chromatography. Ornithine carbamoyltransferase (EC 2.1.3.3) activity in human liver homogenates has been measured using 14C-labeled ornithine and unlabeled carbamoyl phosphate. A thin-layer chromatographic (TLC) procedure is used to separate the radioactive substrate and product, ornithine and citrulline, respectively, and the regions of the chromatogram corresponding to ornithine and citrulline are cut out and counted in a liquid scintillation spectrophotometer. The method has the following advantages: (1) the radioactive substrate ornithine is more stable in solution than carbamoyl phosphate, (2) 14C-labeled ornithine is available in higher specific activity than carbamoyl phosphate, (3) all radioactivity may be accounted for by using the TLC system, (4) the developed thin-layer chromatogram is stable indefinitely, (5) in contrast to colorimetric assays, other compounds in the raction mixture do not interfere with the citrulline determination, and (6) most importantly, the rate of the enzyme reaction at various time intervals can be determined by taking aliquots from the same incubation tube.


Accurate photodensitometric measurement of the lecithin: sphingomyelin ration after elimination of the acidic phospholipids from extracts of amniotic fluid specimens. Treatment of human amniotic fluid lipids dissolved in a chloroform/methanol (9:1, v/v) mixture by batchwise addition of diethylaminoethyl cellulose in a dry state proved to be an easy and rapid procedure for the removal of the acidic phospholipids which may interfere in the photodensitometric evaluation of the lecithin: spingomyelin ratio on a thin-layer chromatogram. This method was used for the measurement of the lecithin: sphingomyelin ratio in a series of normal and abnormal pregnancies. Ratios higher than expected from gestational age were observed in stressed pregnancies. A significant elevation of the ratio was also observed under treatment by dexamethasone.


Outcome of sub-total thyroidectomy for thyrotoxicosis in Iceland and Northeast Scotland. A comparative study of the outcome of surgical treatment for thyrotoxicosis was carried out in two countries with dissimilar dietary iodine levels. In the area with a high iodine level (Iceland) the prevalence of post-operative hypothyroidism was five times lower, but recurrent hyperthyroidism was five times higher, than in the area with lower iodine levels (northeast Scotland). The total morbidity reached comparable levels in the two samples. The prevalence of positive thyroid antibody tests and serum thyrotrophin levels was lower and the functional capacity of the thyroid remnant higher in the area with the higher dietary iodine intake. The study provides further evidence that there are important regional differences in the prevalence of factors known to influence the response to surgical treatment of thyrotoxicosis which should be taken into account when planning treatment services.


Thyroid function in normal subjects in Iceland and Northeast Scotland. A comparative study was made of thyroid function in samples of 'well' subjects, from separate geographical areas with dissimilar dietary iodine levels. In the area with the higher iodine level, Iceland, the prevalence of positive thyroid antibody tests and serum thyrotrophin levels were lower, while the capacity of the thyroid to respond to exogenous thyrotrophin was higher than in NE Scotland, an area with lower iodine levels. In contrast the prevalence of positive tests for another organ-specific antibody, gastric parietal cell antibody, was higher in Iceland. These observations are consistent with the reported differences in the incidence rates for thyrotoxicosis and gastric carcinoma in the areas studied. The results are in agreement with our findings in two groups of post-thyroidectomy patients from the same populations. This study provides support for the view that differences in the prevalence of constitutional and environmental factors in different populations contribute to the variation in reported outcome of treatment for thyroid disease.


Thyroid function in dietary amenorrhoea. Abnormalities of thyroid function are well known to occur in anorexia nervosa. A commoner problem is the patient with secondary amenorrhoea due to weight loss, who does not have true anorexia nervosa. Eight such patients were studied and compared to a normal control group. Total and free thyroxine, total and free triiodothyronine were found to be significantly lower in the amenorrhoea patients. No difference in basal thyroid stimulating hormone or reverse triiodothyronine levels were found. In three of four patients who had thyrotrophin releasing hormone tests performed a prolonged response was found. These results indicate that abnormal thyroid function tests may be found in this milder form of the disease. In addition, the normal reverse triiodothyronine levels suggest the possibility of two mechanisms existing, whereby T3 levels may be lowered in nutritional disorders.


Electrolaryngography in laryngeal disorders. This study was designed to analyse recordings of vocal fold vibrations using the laryngograph, a machine which measures the change in electrical impedance across the larynx. Recordings were made of each patient reading a standard text. The output was analysed in two ways: by study of waveform, and by production of a frequency distribution curve, this last being performed by a PDP 12 computer. Analysis shows an increase in the low frequencies and irregular curve associated with hoarseness but no pattern specific for different diseases. After operation and speech therapy an objective measure of success or failure is provided. But for practical use other than in research a less time consuming method of analysis is necessary. Production of this is being considered.


The clinical use of radiological examination of the maxillary sinuses. Two hundred and eighty-six patients were exposed to puncture and irrigation of 468 maxillary sinuses after completion of radiological examination. The radiological interpretations were made by the same radiologist and related to the clinical rate of demonstrable antral fluid in fully and not fully developed sinuses. Radiologically normal sinuses contained fluid in patients over the age of twelve in 15.3% and when under that age in 39%. The radiological findings should not override one's clinical judgment, and the age of the patient should be considered when conclusions are to be drawn from the radiological findings.


Evaluation of patients with bronchial carcinoma. Results of diagnostic procedures are presented on 259 successive patients with bronchial cancer at Päivärinne Chest Hospital during the period 1967-73. The most common tumours were epidermoid (56%), 'small cell' (20.5%) and adenocarcinoma (9.5%). In 106 patients (41%) chest radiography suggested a tumour, though bronchoscopy was normal, and in 22 cases (8.5%) the radiograph was normal but bronchoscopy revealed a tumour. In 10 (4%) both the radiological and the bronchoscopic findings were normal. A definite histopathological diagnosis was reached by bronchoscopy in 144 patients (44%), by mediastinoscopy in 14 (5%), by fine needle biopsy in 28 (11%) and operatively in 103 (40%). Using all methods of treatment prognosis was significantly better in the group that had been diagnosed by mass miniature radiography, or accidentally (29% alive) as compared with those who had symptoms of the disease (6%).


The use of Proplast in experimental middle ear surgery. The results of the use of Proplast, a new alloplastic material, in experimental middle ear surgery are described. This material was tested for cavity obliteration, closure of bony defects and as a columella between the tympanic membrane and the medial wall of the middle ear. Proplast was well tolerated in the middle ear cavity even in cases with inflammation of the middle ear. The implants were integrated within the recipient tissue by fibrous ingrowth occurring within one week. Bony ingrowth was observed in those cases where the implant contacted the bony wall within 3 weeks. Proplast which supported the tympanic membrane was infiltrated by fibrous tissue and incorporated in the lamina propria. No significant side effects were observed in a 6-month follow-up period although a possible influence on bone remodelling could not be fully excluded.