Reproduction of twelve routinely used ECG leads from three orthogonal ones. The paper presents the results of the reproduction of routinely used leads from three corrected orthogonal leads in the system SVEC III modified by L. I. Titomir. Simultaneously with routine and reproduced leads, the differences among them were recorded at every instant of time. In the reproduction for each proband and each lead an individual selection of vector parameters for the given lead was performed. This method was applied in the examination of 150 probands, including 121 patients with myocardial infarction (MI) and 29 healthy subjects. A comparison of routine with reproduced leads showed that in both healthy subjects and patients with MI the limb leads were well reproducible; reproduction of thoracic leads was poorer, especially in patients with MI. Greatest reproduction errors occurred in leads V2 and V3. In 12.5% of patients with anterior-wall infarct, the diagnostically highly important indicators, pathological Q and informative T waves, were not reproduced. The authors assume that in isolated anterior-wall MI, which manifests itself solely in leads V2 and V3, diagnostic errors occur when only three corrected orthogonal leads are used.


Sex chromatin in cardiovascular diseases in elderly and senile women. In women aged 60--79 years the author determined the frequency of sex chromatin in epithelial cells of buccal mucosa. A higher frequency was found in women with cardiovascular diseases, especially with arterial hypertension and acute disturbances of coronary of cerebral circulation. The role of hormonal factors in the pathogenesis of cardiovascular diseases in elderly women is discussed.


Brain and kidney renin-angiotensin activity in spontaneously hypertensive rats. Renin activity in peripheral plasma (PRA), renal cortex and brain tissue (cortex, stem, medulla oblongata) homogenates was studied in a bioassay after Serebrovskaya's modification of the method of Pickens. Fourty-nine spontaneously hypertensive rats (SHR) and 26 normotensive Wistar rats (NWR) were used. The results show that: 1) In spite of very high systolic blood pressure, PRA in SHR is in normal ranges; 2) Renin activity exists not only in the brain of NWR, but in the brain of SHR as well. 3) Renin activity in the different parts of the brain is not equal both in NWR and in SHR. 4) Renin activity in the cortex, the stem and the medulla oblongata of SHR is in normal ranges. 5) Renin activity in the medulla is higher than in other areas of the brain, both in NWR and in SHR, the difference being statistically significant in the latter. 6) No perceptible interrelation between arterial blood pressure, PRA, renal renin activity and renin activity in the cortex, and in the stem of the brain was established. It is suggested that higher renin activity in the medulla oblongata might be considered as an indication of the importance of the brain renin-angiotensin system, and its function in the cerebral (neural) regulation of the cardiovascular system. A causal connection between the renal and the brain renin-angiotensin systems, and the onset and maintenance of hypertension is assumed.


Measurement of systolic time intervals through non-invasive polygraphic techniques in healthy subjects and in patients with ischaemic heart disease. Comparison of results obtained by conventional and computer assisted means. Computer processing of carotidograms is an incontestable methodical asset. Electronic detection of systolic time intervals excludes human errors, makes possible evaluation of a greater number of systoles, and reduces the effect of nonlinearities of recording. The proposed computerized system saves tedious manual calculations and can yield results with mutual correlations within a short period of time.


Intramitochondrial calcification and myocardial inclusions in the rabbit due to anoxic hypoxia. Intramitochondrial calcium granules and calcification of the mitochondrial cristae were examined in myocardial cells of rabbits in acute anoxic hypoxia, under normal circulation. The alterations were noted first after 2 hours of hypoxia, and became progressively larger and more ubiquitous with increasing periods of anoxic hypoxia. After 8 hours or longer hypoxia intramitochondrial "cristalloids" were found in some mitochondria.


Left ventricular end-diastolic volume during supine exercise in patients with healed myocardial infarction. Eighteen men with myocardial infarction in their history and without signs of heart failure were investigated at rest and during standard supine exercise. In nine patients aneurysma or diskinesis of the left ventricular wall were found. The left ventricular end-diastolic volume was determined from the wash-out of 133Xe injected into the left ventricle by means of precordial scintillation counting. During exercise the cardiac index rose owing to acceleration of the heart rate, whereas the stroke index remained unchanged, and the left ventricular work and stroke indices increased. The left ventricular end-diastolic pressure, elevated at rest, reached high values during exercise. The left ventricular end-diastolic and residual volumes decreased during exercise in most patients, and simultaneously the systolic ejection fraction increased. In patients with aneurysma or diskinesis the end-diastolic volume both at rest and during exercise does not differ from EDV of other patients. Six patients developed angina pectoris during exercise, but their haemodynamics did not differ significantly. It is concluded that the left ventricle in patients with advanced coronary heart disease and previous myocardial infarction shows the signs rather of diminished compliance than of heart failure during adequate exercise and still possesses some functional reserves.


Management of Reye's syndrome. A rational approach to a complex problem. Five patients suffering from progressive Reye's syndrome were aggressively treated in our ICU. Our protocol consisted of endotracheal intubation, curarization, mechanical ventilation, hypothermia to 31 degrees C, and fluid restriction. Intracranial pressure (ICP) was monitored and remained below 10-20 torr in all patients except one in whom ICP rose only once (for a few minutes) to 27 torr. Pulmonary artery wedge pressure was monitored in 4 patients and was maintained at 4-5 torr. Duration of active intervention as outlined above was 3-4 days. All 5 patients started with clinical stage IV and EEG grade IV or worse. Four patients had complete recovery and one died. In this group of patients, high ICP was not a feature of the disease. We recommend that use of mannitol for active dehydration be reserved for cases with proven rise in ICP, in which case hemodynamics should be carefully monitored.


First annual Herbert S. Shubin Memorial Lecture. Acute circulatory failure (shock) associated with cardiogenic pulmonary edema. Our findings confirm that acute pulmonary edema, when caused by left ventricular failure, represents a form of acute perfusion failure (shock) with metabolic acidemia, lactacidemia, and a reduction in forward blood flow. It is associated with a marked increase in peripheral resistance and an increase in venous capacitance. Most importantly, acute pulmonary edema is associated with a reduction in the intravascular blood volume. Acute pulmonary edema is not fundamentally different from other types of shock in which the shock state is initiated by one primary defect, and during the course of its progression, other primary mechanisms are called into action. In the instance of acute cardiogenic edema, the primary defect is cardiac pump failure and the secondary defects include hypovolemia and distributive defects associated with arterial vasoconstriction and expanded venous capacitance. Furosemide reverses acute pulmonary edema by increasing rather than decreasing intravascular blood volume with consequent improvement in the distributive and hypovolemic defects. Under extreme conditions, the volume defect in acute pulmonary edema may be so great that the patient presents with primary hypovolemia. The utilization of volume repletion is warranted under these circumstances.


Relation between lowered colloid osmotic pressure, respiratory failure, and death. Plasma colloid osmotic pressure was measured each day in 84 intensive care unit patients. Probit analysis demonstrated a direct relationship between colloid osmotic pressure (COP) and survival. The COP associated with a 50% survival rate was 15.0 torr. COP was higher in survivors than in nonsurvivors without respiratory failure and in patients who recovered from respiratory failure. We conclude that lowered COP is associated with an elevated mortality rate. However, the relationship to death is not explained by the relationship to respiratory failure.


Modern approach to the patient with acute myocardial infarction. This presentation has described the modern approach to the patient presenting with chest pain suspected as acute myocardial infarction. Noninvasive and invasive methods have been applied to estimate the extent of the myocardial damage and to monitor the electrical, hemodynamic and metabolic changes during the acute phase. In addition to the use of standard analgesics and antiarrhythmics, measurement of the determinants of left ventricular function by noninvasive and invasive techniques provides a physiologic basis for administration of available pharmacologic agents that can alter the afterload, contractile state, preload, heart rate, metabolic state and infarct size. Information from the Swan-Ganz catheter can describe hemodynamic categories that can be optimally managed by regulation of the left ventricular filling pressure. Patients managed in this manner can be identified for early hospital discharge at 7-10 days. Other patients less than 50 years of age or those experiencing recurrent arrhythmias, ischemic pain or evidence of left ventricular dysfunction may be candidates for coronary arteriography and left ventricular angiography before hospital discharge.


The role and function of an Australian intensive care unit. A detailed report on the activities of a major Australasian ICU is presented. An adequate team of specially trained medical and nursing staff is required to function efficiently. Despite a linear increase in admissions and a broadening scope of references, mortality  has remained constant. Practice of Intensive Care Medicine must not be confined solely to special units. Involvement in other hospital areas is described.


Neurological complications of osteopetrosis. The clinical course of twins with osteopetrosis has provided a catalogue of the neurological complications that may occur with the disorder. Such a list has not previously been compiled: (1) Hydrocephalus - probably due to outflow obstruction in the posterior fossa. (2) Sagittal sinus thrombosis - due to bony encroachment, or to hematological causes. (3) Exophthalmos - due to bony encroachment in the orbit. (4) Foraminal occlusion at the base of the skull, producing compromise of cranial nerves and vessels. (5) Paraparesis - cause unknown, perhaps due to spinal stenosis. (6) Anemia - myelophthisic, although a hemolytic component due to hypersplenism has been identified, as well.


Hypothalamic tumors in children. Their diagnosis and management. 17 intrinsic hypothalamic tumors in infancy and childhood occurring between 1963 and 1973 were analyzed in detail because of the consistent mode of approach to diagnosis, therapy and follow-up care. Careful examination of the symptom-time sequence and location provided anatomical-clinical correlations and was even suggestive of the probable histologic type of lesion present. The postoperative and long-term management problems have led to significant conclusions. The best results were obtained with those patients who underwent craniotomy and biopsy, followed by irradiation therapy.


Ependymomas of childhood. II. Electron-microscopic study. Electron-microscopic study of various histological types of ependymoma has shown three basic types of cells. One type of cells has features typical of normal ependymal cells, the second type consists of cells resembling normal or reactive astrocytes, and the third type of cells is undifferentiated. The three types of cells are present in various proportions in every tumor. Generally speaking, the astrocyte-like cells are more frequently encountered than the ependymol cells. The undifferentiated cells are seen, in small numbers, in all forms of ependymoma but they are the dominant cell type in the ependymoblastomas.


Craniolacunia in newborn with myelomeningocele. Plain skull films were taken within 7 days of birth in 34 newborn with myelomeningocele. There appears to be a correlation between hydrocephalus or Arnold-Chiari malformation and the severity of craniolacunia. Craniolacunia was observed in 28 cases (82%). The incidence of craniolacunia in myelomeningocele in this series is higher than in previous reports. One of the reasons is that plain skull films of newborn with myelomeningocele are usually not taken early at birth. We would like to emphasize that plain skull films be taken early at birth in newborn with myelomeningocele and that the presence of craniolacunia be considered as being associated with hydrocephalus and the Arnold-Chiari malformation.


Congenital meningioma.

Congenital meningioma. The clinical, operative and autopsy findings associated with a huge meningioma in an 8-month-old boy are described. Especially noteworthy are the patient's age, the size of the tumour and the poorness of neurological symptoms.


Congenital brain defect masked by subdural fluid collection. Two rare cases of subdural fluid collection are reported. In these cases, the subdural space was in direct communication with the lateral ventricle through the congenital brain defects. The subdural fluid was formed by the cerebrospinal fluid which passed from the lateral ventricle through the brain defects. The difficulty to diagnose these cases from the usual subdural hygroma is emphasized.


[Capsular arthroplasty of the elbow joint for the treatment of recurrent dislocation. Personal results in comparison with case reports in literature. Indication--methods--after care]. Four cases of recurrent dislocation of the elbow joint are reported. Instability of the postero-lateral ligaments were found in all patients, both clinically and during operation. In one case there was also instability of the medial ligament. Lateral instability is regarded as the primary lesion responsible for recurrent dislocation. Intraarticular pathological lesions such as osteochondral fractures were also diagnosed in our patients. All were treated by a capsuloligamentous repair as proposed by Osborne and Cotterill [8]. Based on follow-ups of 2 to nearly 5 years no recurrences were seen. The patients were free of pain with a nearly full range of motion. Considering the results reported in the literature of cases treated by the same method, the authors are convinced that the operation repairs the essential lesion.


[Habitual scapholunar dissociation].

[Habitual scapholunar dissociation]. The authors discuss a rare form of wrist injury, involving scapholunar dissociation, which is manifested by subluxation of the scaphoid bone. The radiologic, clinical, and therapeutic aspects are described. The authors also represent a case of their own where the subluxation of the scaphoid bone became habitual.


[Dysphagia as a symptom of idiopathic fibrous mediastinitis]. A case of idiopathic chronic fibrous mediastinitis accompanied only by dysphagia is reported. Symptoms, etiology, and differential diagnosis are discussed with reference to the literature reviewed. The various conservative and operative methods of treatment are presented. In this case, attempts to mobilize the oesophagus were unsuccessful. Therefore, the oesophagus was bypassed via the colon.


[Delayed surgery in acute pancreatitis]. In 32 patients with acute pancreatitis, delayed operation was performed between 13 and 44 days after onset of the illness. The indications for the operation were development of a palpable mass together with clinical deterioation and other complications. In all patients we found a necrotizing pancreatitis and/or abscesses of the pancreas. The surgical procedure consisted of digital removal of necrotic tissue (sequestrotomy) and/or abscess incision in 20 patients, of left-sided resection in 11 patients and partial duodenopancreatectomy in 1 patient. Twenty-three patients survived, 9 died.


[Management of upper-bile-duct occlusions using the Rodney Smith method]. This is a report on 10 cases of hepaticojejunostomy (Rodney Smith) with a sutureless technique. The method is very easy and the diameter of anastomosis is more than 5 mm.


[Pseudotumor of the urinary bladder and intestino-vesical fistula in ileitis regionalis (Crohn's disease) and diverticulitis. Surgical tactic and technic]. Pseudotumor of the urinary bladder and intestino-vesical fistula caused by regional ileitis (Crohn's disease) and diverticulitis require radical en bloc resection. The authors present their own procedure.


[Experiences with the Erlangen magnetic closure system]. At the surgical hospital of the University of Erlangen/Nürnberg a magnetic closure system was developed for colostomies and ileostomies, which can give continence. Since November 1974 113 magnetic systems have been implanted. We have good results in 31% of the patients, less good results in 16%, and bad results in 53%. The authors demonstrate faults in the indication for the operation and faults in the surgical technique which lead to bad results. Avoiding these faults continence in 70% of patients can be achieved. In no case was the magnetic closure system the reason for bad results.


[Progresses in the treatment of skull-brain injuries in childhood]. In a group of children with severe head injury it was possible to lower the rate of mortality in a comparable group of injured children. Besides consistent neuroradiologic diagnosis and the possibility of immediate neurosurgical intervention, improvement of intensive therapy by monitoring of intracranial pressure and rehabilitation at an early stage brought about significant progress.


[Course of immunoglobulins G and M in seriously burned patients]. IgM and IgM levels were measured in 108 burn patients. A marked decrease was evident in these immunoglobulins. The initial fall of IgG can be attributed to the loss of serum via the body surface, i.e. burn blisters. The loss of IgM may be taken as indication of the catabolic phase. Quantitative substitution was possible in almost all cases.


[Factor XIII deficiency in burns].

[Factor XIII deficiency in burns]. In 34 patients with severe burn injuries platelets, fibrinogen, prothrombin time, partial thromboplastin time, thrombin time and factor XIII were measured daily. Half of the patients were administered 15 000 IE of heparin per 24 hours. In the first 4 days there was a rapid fall of factor XIII to a value of approximately 30%. Values remained very low during the whole observation period of up to 20 days. However, in patients treated with heparin, values tended to be 10--15% higher. After an initial decline on the tenth day, the platelets had risen to the lowest normal level. Platelets were identical in both groups. The causes for the changes in these haemostasis parameters, their significance, and possible consequences of therapy are discussed.


[Value of triple diagnosis for the surgical treatment of breast carcinoma]ms. A special documentation in clinical examination of the breast with palpation, mammography, and aspiration cytology (triple-diagnosis) has been used since 1973. In 102 cases of breast cancer, the cytologic examination was, done before operation, in 54% of the cancer cases of primary modified radical mastectomy could be performed without waiting for the frozen section result.


[Drainage-dependent continence disorder after deep resection of the anterior rectum]. Anorectal continence following low anterior resection in 37 controlled patients from the University Hospitals of Innsbruck, Department of Surgery, in the years 1970 to 1974 is described. Of these 37 patients, 10% were partially incontinent for from 18 to 24 months. It is pointed out that the partial incontinence of these patients is due to the extensive perirectal-perianal drainage. The low anterior resection can be called continence-saving, if a too extensive perirectal-perianal drainage is avoided and the criteria of the operation are considered.


Treatment of sessile villous and tubulovillous adenomas of the rectum: experience of St. Mark's Hospital. 1963-1972. Between 1963 and 1972, 121 new patients were treated at St. Mark's Hospital for a sessile villous or tubulovillous adenoma of the rectum. Thirty patients (25 per cent) were found to have simultaneous neoplastic lesions in the large intestine. Sphincter-preserving operations were performed whenever possible, and the various methods of treatment used are analyzed. Fourteen patients (11.6 per cent) had postoperative complications, and three patients died. Twenty-six patients are know to have had further benign tumor at the same site during the follow-up period.


Ileostomates in Israel.

Ileostomates in Israel. A survey of 47 Israeli ileostomates known to the Israel Ostomy Association was performed. The outstanding features are 1) a low (5 per cent) referral rate of patients with inflammatory bowel disease for procto colectomy and ileostomy; 2) a high (64-85 per cent) incidence of cutaneous problems; 3) a low rate of rehabilitation, as measured by return to previous occupation, sexual life and social adjustment. However, our 47 ostomates were operated on 14 institutions in five countries and live in a subtropical climate-factors that may negatively affect the outcome. Since the study, the situation has improved.


Prophylactic oophorectomy in conjunction with large-bowl resection for cancer: report of two cases. This report, based on eight cases of our own and a review of the literature, indicates that colonic cancer metastatic to the ovaries has many unusual features and an extremley high mortality rate. Prophylactic bilateral oophorectomy in conjunction with large-bowel resection for cancer in women of all ages is strongly advised to decrease morbidity and improve the quality of survival.


Malignant appendiceal carcinoid with intussusception of the base manifesting as a cecal tumor: report of a case. A case of an appendiceal carcinoid tumor with regional lymph-node metastases is presented. The size of the tumor was remarkable, as the appendix was infiltrated throughout its length. The proximal part of the appendix was intussuscepted into the cecum. Preoperatively, the lesion was diagnosed as a polypoid tumor of the cecum. A primary right hemicolectomy was carried out.


Herniation through the foramen of Winslow: report of a case. Herniation into the lesser omental sac through the foramen of Winslow is a rare cause of intestinal obstruction. A successfully managed case is presented. The clinical history and physical findings are reviewed, and radiographic findings are discussed. The proper interpretation of these findings should suggest the diagnosis. Treatment is prompt surgical correction, and various technical maneuvers that may be necessary are outlined.


Retrorectal abscess with neurologic involvement of the lower extremities: report of a case. A case of retrorectal abscess with neurologic involvement of both lower extremities is presented. The authors believe that an adequate description of this entity is necessary for the clinician, insofar as rectal suppurations rarely cause neurologic symptoms. The clinician must be alert for the possibility of the presence of various presacral tumors, whose treatment and prognosis present much graver problems.


The use of a curved uterine vulsellum for removal of rectal foreign bodies: report of a case. Removal of retained foreign bodies can be a tedious process, requireing considerable skill and ingenuity on the part of the surgeon. Employment of a curved, double-pronged, uterine vulsellum can be useful in simplifying removal of certain of these objects. A method which can be employed on an outpatient basis is described. When this method fails, suitable cooperation by the patient is lacking, or there is evidence of serious rectal injury or perforation, hospitalization for appropriate treatment under general or regional anesthesia is indicated.


Concomitant administration of haloperidol and lithium carbonate in acute mania. Prospective and retrospective studies of 55 psychotic patients treated concomitantly with oral haloperidol and lithium carbonate did not reveal any evidence of permanent brain damage or persistent dyskinesias; adverse reactions were transient and without sequelae. Results in these patients afford further evidence that combined use of haloperidol and lithium is safe and effective in the treatment of mania. Careful management is essential to minimize the risk of serious adverse reaction.


Alcoholics and high-low sensory input: a pilot study. It is hypothesized that alcoholics possess a perceptual-neurophysiological sensitivity which renders them vulnerable to the effects of information or stimulus overload: the resort to alcohol, therefore, may represent an adaptive attempt to restore physiologic homeostasis through the pharmacologic "dampening" properties of this drug. Twelve alcoholic subjects were assigned to three different levels of audio-visual sensory stimulation (no, medium, high) and three different doses of alcohol (placebo, low, high) according to a balanced incomplete block design. The results indicated trend level and significant interactions between alcohol and sensory level effects on craving intensity and systolic blood pressure, respectively, as well as a number of other intriguing findings. Should the findings of this pilot study be replicated, they will have important implications for the understanding of alcoholism.


The medication clinic in the spectrum of children's services. The use of stimulant drugs for control of hyperactivity in children led one mental health center to centralize the procedure in a medication clinic. A number of benefits were derived from monitoring the children through routine folow up visits. One of the retrospective findings over a three-year period was the low incidence and prevalence rates of medicated hyperactive youngsters in a high volume children's service.


Brain death.

Brain death. Brain death occurs whenever there is involvement of higher centers such as Cerebral Cortex and Thalamus (unresponsiveness and deep coma) and Brainstem and Basal ganglionic structures (loss of spontaneous respiration all cranial nerve, and postural reflexes). Involvement of Spinal Cord is less constant. Drug intoxication should be excluded. An electroencephalogram may be done but what is paramount is the physician's clinical judgment. The medico-legal implications of brain death is less complicated than it is generally presumed to be. It is extablishment of the legality of brain death concept that is crucial. This allows the physician to use his judgment to implement the law.


Electrocardiographic findings in patients undergoing amitriptyline treatment. Fifteen depressed patients were treated with amitriptyline in a dosage ranging from 75 mg to 200 mg/day for a minimum of three weeks, two of which were at a fixed dosage. Plasma samples were drawn 12 to 16 hours after the bedtime dose of medication for determination of amitriptyline and its metabolite nortriptyline. Electrocardiograms were taken prior to treatment and after three weeks of drug treatment. The only abnormality noted prior to treatment was bradycardia in one patient. After treatment, two patients exhibited nonspecific T-wave abnormalities. Otherwise, the electrocardiograms were unremarkable. A significant increase in heart rate (p less than 0.001) was noted. The mean increase in rate was sixteen beats per minute. Those patients having a rate change greater than sixteen beats per minute had significantly higher amitriptyline levels (p less than 0.05), and total tricyclic antidepressant levels (p less than 0.05), than those patients having a mean rate increase less than sixteen. While tricyclic antidepressants can produce multiple cardiac effects, the risk of cardiac morbidity and mortality is relatively low in patients undergoing tricyclic antidepressant treatment with moderate dosages.


Psychotic pica, nicotinism, and complicated myocardial infarction. The authors report a case of a schizophrenic patient who repeatedly consumed a wide variety of inedible materials, including significant quantities of tobacco. The phenomenology of this behavior, as well as its psychiatric and medical complications are discussed. It is probable that chronic nicotinism contributed to this patient's refractoriness to psychiatric treatment and to his eventual cardiovascular crisis. The occurrence of pica as a manifestation of severe psychopathology was vividly described by the early pioneers of neuropsychiatry, but has received little attention in recent psychiatric literature. This is in marked contrast to the syndrome of psychogenic water intoxication which continues to be reported frequently. The majority of descriptions of pica have dealt with its occurrence in children, in pregnant women, and as a societal practice in certain cultures studied from a medico-anthropologic point of view. The toxic organic brain syndrome caused by chronic ingestion of nicotine-containing products has also been neglected in psychiatric publications. Descriptions of the neuropsychiatric complications of subacute and chronic nicotinism have been restricted to textbooks of toxicology, where greater emphasis has been given to the acute effects of large quantities of nicotine, often in forms other than tobacco. The following case illustrates the near-fatal practice of tobacco pica in a psychotic patient and dramatically demonstrates the systemic and central nervous system effects of nicotinism.


Catatonia and systemic lupus erythematosus. Catatonia has generally been assumed by many physicians to be a subtype of schizophrenia. Numerous cases have been reported in the literature associating catatonia with other psychiatric and also medical illnesses. The present report describes a patient with Systemic Lupus Erythematosus (SLE) who presented in a catatonic state. A brief differential diagnosis of catatonia is also included.


Spontaneous improvement in "normal" pressure hydrocephalus. A patient is presented with "normal" pressure hydrocephalus including dementia, incontinence, and apraxic gait. He had a normal lumbar CSF pressure, hydrocephalus with lack of air over the convexities on pneumoencephalography, and ventricular filling with prolonged retention on cisternography. He did not receive a shunt and, nevertheless, showed spontaneous improvement in his mental function over the next few years. This cases emphasizes the necessity for a controlled study of shunting for "normal" pressure hydrocephalus.


Masking of tardive dyskinesia with four times-a-day administration of chlorpromazine. Two chronic schizophrenic out-patients with tardive dyskinesia were treated with chlorpromazine in 2 regimens -- once-daily and four times-daily -- using a cross-over design. Two "blind" raters evaluated the severity of symptoms of tardive dyskinesia, pseudoparkinsonism and schizophrenia on rating scales every week during the 14-week-trial period. Results showed that the intensity of dyskinesia was significantly lower, and that of pseudoparkinsonism higher (but not significantly) with Q.I.D. than with O.D. medication. Symptoms of schizophrenia did not vary in severity appreciably with the two frequencies of drug intake. It is suggested that multiple-dose administration of a phenothiazine maintains a steady level of dopamine blockade throughout the day and thus masks the manifestations of tardive dyskinesia.


Corneal topography.

Corneal topography. This paper explores the many aspects of the nature and measurement of the corneal surface. Its structure and the factors that influence it are described. The traditional techniques of keratometry are summarized and there is an emphasis on new experimental methods of determining corneal topography including moiré, holographic interferometric and profile techniques. The advantages and disadvantages of these procedures are considered.


On the individual pressure tolerance of the glaucomatous eye. The individual pressure tolerance of any eye can be determined by taking account of the age, the values of the mean arterial pressure APm, the C/D ratio and the degree of deterioration of the visual field. The method developed opens the way to new possibilities in anti-glaucomatous therapy by making it possible to know the value of the maximum pressure (IPT) which can be supported by the eye under treatment. That treatment must succeed in reducing the value Pi to below the value IPT, if it is to be hoped that the evolution of the glaucoma will be stopped.


Spheroidal degeneration of the cornea. Prevalence and association with other eye diseases. A sample of 2,427 South African Negroes of the Pondo tribe was specifically examined for spheroidal degeneration of the cornea (S.D.C.). The prevalence of S.D.C. was 7.0% for the whole sample. It was twice as prevalent in men (9.9%) as in women (4.3%) and the prevalence increased with age over 50 for both sexes. The risk of having developed Stage II and III S.D.C. increased with age for men but not for women. The risk of having developed Stage III S.D.C. was not related to age or sex. No significant associations were found between S.D.C. and pterygium, cortical or nuclear cataract and glaucoma (all types and absolute glaucoma). There was a significant association between S.D.C. and pseudocapsular exfoliation for elderly men but elderly men with arcus senilis were less likely to have developed S.D.C. Poor corneal nutrition or metabolism are possible aetiological factors in the progression of S.D.C. to Stages II and III.


[Patient's understanding of their illness and patient-doctor relationship in the out-patient clinic (author's transl)]. 96 randomised outpatients of the Medical University Policlinic at Basle were interviewed at their first medical examination: 88 patients were told their diagnosis. Afterwards 76 were able to name the diagnosis correctly, with 55% showing good, 26% mediocre and 19% insufficient understanding of their illness. This understanding was influenced by profession, age and sex. With the aid of 25 medical terms familiar to a layman, basic medical knowledge of the patient was tested. Half of the questions were answered correctly, with a good correlation between understanding of the disease and basic medical knowledge. Half the patients complained of having insufficient comprehension of the medical explanation of their illness, the main reason being the use of latin terms by the doctors. Better medical information of the public, and conscientious and comprehensive explanation of the illness by the doctor are obviously essential conditions for the better understanding of his disease by the patient.


[New aspects of the pathogenesis and treatment of haemorrhoids (author's transl)]. Blood flow out of the corpus cavernosum recti (which has an arterial blood supply) was studied by injection of veins in the anorectal region. Venous flow occurred across the sphinctre and proved of considerable significance in the pathogenesis of haemorrhoids. An understanding of the pathomorphological changes in the three stages of haemorrhoid development made appropriate therapeutic consequences possible.


[Spontaneous platelet aggregation associated with administration of sex hormones in men and women (author's transl)]. Spontaneous platelet aggregation was measured by an identical rheological method in 19 women and 17 men. Eight of the women (average age 26 years, range 19-56) were at the time on oral contraceptives (group A), the other eleven (average age 26, range 19-50 years) served as controls (group B), as did 17 men (group C) of similar age (average 28, range 22-50 years). Mean maximal aggregation amplitude was significantly greater in group A than B and C (P less than 0.05 and less than 0.025, respectively), which makes it probable that there was a greater tendency to aggregation of the blood platelets under the influence of the oral contraceptive.


[Regional suppurative lymphadenitis after BCG vaccination (author's transl)]. In the first half of 1975 there occurred in the Federal Republic of Germany an unusual rise in the incidence of suppurative inguinal lymphadenitis after BCG vaccination of newborns, in immediate time relation with change of the vaccine by its manufacturers, Behringwerke. The attenuated daughter strain Göteborg had been replaced by the effective but also rather aggressive strain Copenhagen 1331. The complication rate was 1.5% in West Berlin. Clinical course, operative technique as well as microbiological and histomorphological features of these cases were analyzed in a joint study. Since it is likely that, after re-admission of the Copenhagen vaccine, such complications may again occur despite reduced micro-organism count, vaccination of newborns should in future be restricted to those at risk.


[Agranulocytosis due to cotrimoxazole in a seven-year-old boy (author's transl)]. A seven-year-old boy presented with agranulocytosis after receiving cotrimoxazole for eight days. Three years previously he had had another episode of untoward reaction to the drug with transient, mild leucocytopenia. But four periods of cotrimoxazole treatment in the intervening years had been tolerated without complications. There was no improvement in the critical state of the child while on broadspectrum antibiotics, until granulocytes reappeared in peripheral blood. This reaction to cotrimoxazole, although extremely rare, requires serial white blood cell and granulocyte counts during repeated and prolonged cotrimoxazole administration, if signs or symptoms of infection persist.


[Percutaneous puncture of the femoral vein for haemodialysis: report of 5000 punctures (author's transl)]. Using the Seldinger technique, a total of 5306 percutaneous femoral vein catheterisations were performed in the course of ten years. Two-catheter venovenous dialysis was performed 2357 times and single-needle technique 592 times. There were five important complications: severe retroperitoneal bleeding after perforation of the external iliac vein three times, fatal bleeding from the femoral artery once, and reversible damage to the femoral nerve once. The results indicate that for every 1000 percutaneous femoral-vein catheterisations one must expect one severe complication. However, by using the correct catheter technique, especially careful manipulation of the wire, complications can be largely avoided.


[Progress in the differential diagnosis of myocardial infarction by determining isoenzyme CK-MB with inhibitory antibodies (author's transl)]. Sensitivity and value of the quantitative measurement of the isoenzyme creatine kinase-MB by means inhibitory antibodies were studied in a number of experiments. The results indicate that concentrations of more than 3 U/1 are abnormal: they were found only in patients with myocardial cell damage but not after intramuscular injection or physical exercise. Determining CK-MB apparently offers a better way of assessing low or moderate increases of total CK activity than, e.g., the CK/GOT ratio. The method should therefore be introduced into clinical diagnosis. But the question of whether CK-MB measurement can differentiate between myocardial infarction and reversible myocardial cell damage remains unanswered: it is not 100% specific for myocardial infarction.


[Low-dose heparin and acetyl-salicylic acid after elective operations on the hip joint (author's transl)]. 3.6 g acetylsalicylic lysin was injected into 30 patients daily after operative replacement of the hip-joint. Pulmonary embolism and (or) deep-vein thrombosis were diagnosed in 19 patients. Low-dose heparin (3 X 5000 IU/24 h) significantly reduced the incidence of deep-vein thrombosis (ten of thirty patients: P less than 0.05) compared with the acetylsalicylic acid group. The results demonstrate not only the inadequate thrombosis prophylaxis provided by acetylsalicylic acid, but also that low-dose heparin prophylaxis in these specially at risk patients is of limited efficacy.


[Hyperreninism without hyperaldosteronism in diuretic abuse: a report of a case with identification of mefruside and ethacrynic acid in urine (author's transl)]. A 46-year-old nurse had been hospitalized 16 times during the preceding five years because of episodes of excessive hypokalaemia. On admission to hospital there was hypokalaemia, polyuria, excessive plasma renin activity but no increased aldosterone secretion rate. Diuretic abuse was confirmed by gas-chromatography and mass spectrometry of mefruside and ethacrynic acid in the patient's urine. Apart from other interesting aspects of this case there was the demonstration of hyperreninism without hyperaldo-steronism. The stimulating effect of renin on aldosterone secretion was obviously lower than the inhibiting effect of hypokalaemia. The general term "renin-angiotensin-aldosterone system" is, therefore, misleading because it mentions only one pathway of aldosterone regulation. The combination of hypokalaemia, polyuria, hyperreninism without hyperaldosteronism is apparently the principal but not widely recognised feature of diuretic abuse.


[Digitalis effects on the electrocardiogramm: ergometric studies in healthy subjects and patients with coronary artery disease (author's transl)]. Therapeutically effective doses of beta-acetyldigoxin in healthy subjects produced no or only minor S-T depression both at rest and under maximal cycle-ergometry, in individual instances the S-T segment never being depressed by more than 0.1 mV. On the other hand, similar exercise in patients with latent coronary insufficiency produced marked, significantly and dose-dependent S-T segment depressions under increasing digitalisation within the therapeutic range, and in some of the patients there was also decreased exercise tolerance before anginal symptoms. It is concluded that the so-called digitalis effect is definitely of diagnostic significance in the recognition of latent coronary insufficiency, contrary to previously held belief.


[Fetoscopy under ultrasound control (author's transl)]. Under local anaesthesia and ultrasound control (beta-mode; Vidoson) the fetoscope was introduced into the amniotic cavity in 23 women, 13-20 weeks pregnant. Used before planned surgical abortion the method decisively reduced the dangers of damage to the fetus. In 21 women introduction of the fetoscope was without problem, but twice obesity made it difficult. Placental surface, umbilical cord, fetal head and fetal limbs were more commonly seen than other fetal parts. In one instance fetoscopy made it possible to exclude Mohr's syndrome. Preliminary attempts to obtain fetal blood by puncture of placental vessels under fetoscopy were successful. The described technique seems highly promising. Further experience will demonstrate whether it is without danger and simple enough to be used routinely in the prenatal diagnosis of congenital anomalies.


[Abnormal myocardial blood flow pattern after non-transmural infarction (author's transl)]. While coronary angiography was within normal limits in three patients with recurrent severe attacks of angina and non-transmural postero-lateral wall myocardial infarction, myocardial perfusion scintigraphy demonstrated an abnormal distribution pattern. In addition to recanalised thrombosis, embolism or spasm, abnormalities in the microcirculation are possible causes of the discrepancy between the coronary arteriogram and the scintigram. Myocardial perfusion scintigraphy is of particular diagnostic significance in this group of patients with coronary heart disease but normal coronary angiography. Treatment in the presence of this finding consists of administration of platelet-aggregation inhibitors.


[Cutaneous iontophoresis of hyaluronidase in the treatment of hemorrhages in hemophilic patients]. After a surgery of the theoretical background of iontophoretic technic and the physico-chemical properties of hyaluronidases, a clinical application is presented, based on over 500 hemophilic patients treated percutaneously, in cases both of hemarthrosis and hematomas. The results are presented and discussed. The conclusion is that hyaluronidase iontophoresis is useful and should be performed together with the other measures for the prevention and the treatment of the damages produced by hemorrhages in hemophilic patients.


Blood biochemical alterations during recovery from competitive marathon running. The occurrence of possible prolonged alterations in plasma levels of cortisol, epinephrine, norepinephrine, selected energy metabolites, and water and electrolyte balance was assessed in six highly trained male marathon runners by measuring blood biochemical constituents on the 10th day before and for the three days following the running of a marathon. Post-race changes in hemoglobin, hematocrit, and protein levels indicated that a hemodilution had occurred, possibly as a result of elevated sodium levels. Epinephrine remained elevated until the second day. Cortisol was depressed on the first and third post-race days while variable levels were observed on the second day. No prolonged alterations were noted in norepinephrine, FFA, glycerol, triglycerides, glucose, lactate, and pyruvate.


Failure of noise  exposure to modify temporal patterns of plasma cortisol in man. The purpose of this investigation was to assess the modification in the temporal pattern of plasma cortisol levels during exposure to noises of different intensities, frequencies and durations. Plasma cortisol concentrations were measured from 08.00 h to 15.00 h at 10 min intervals in eight subjects on a control day and one or two exposure days. Noise exposures induced no significant increase in plasma cortisol concentration. It is concluded that noise, at "safe" levels for human hearing conservation, when not associated with other potentially noxious stimuli does not cause hyperactivity of the pituitary-adrenocortical system. These results do not tally with those from animal studies where noise is known to activate corticotrophin (ACTH) secretion.


Effect of glucose ingestion on energy substrate utilization during prolonged muscular exercise. The distribution of substrates utilized during prolonged exercise was investigated in normal human volunteers with an without ingestion of 100 g exogenous glucose. The energy provided by protein oxidation was derived from urinary nitrogen excretion and the total energy provided by carbohydrates and lipids was calculated from respiratory quotient (RQ) determinations. The contribution of exogenous glucose to the energy supply was determined by an original procedure using "naturally labeled 13C-glucose" as metabolic tracer. Protein oxidation provided between 1 and 2% of the total energy requirement; this amount was not affected by glucose ingestion. In the absence of exogenous glucose ingestion, carbohydrate were progressively replaced by lipids as source of energy. Exogenous glucose contributed markedly to total carbohydrate oxidation and decreased the percentage of energy derived from lipids. In addition, ingestion of exogenous glucose resulted in a significant economy of endogenous carbohydrates and permitted to prolong the duration of exercise.


Muscle amino acid arylpeptidases and their serum changes with exercise. Activities of serum amino acid arylpeptidases were determined in five groups of healthy male adults at rest and after various exercise types using the following substrates: Ala-, Leu-, Phe-, Tyr-, Gly- and Pro-4-Nitroanilide. The exercise-induced changes were compared to the activities of the respective enzymes in resting leg muscles. A regression function was found, showing a close correlation between the mentioned parameters in all groups. The influence of haemoconcentration and intravascular hemolysis on the postexercise measured activities was of no consequence.


Regional blood flow in response to exercise in conscious dogs. Regional blood flow was measured with the microsphere method in conscious dogs under resting conditions and during moderate exercise on the treadmill. With respect to total organ blood flow, exercise induced a marked increase in blood flow to the calf muscles and to the myocardium, and a significant decrease in the arterial blood supply to the liver. Slight changes in blood flow to the other organs under study (various skeletal muscles, skin, brain, kidneys, intestine) were not significant. Study of the blood flow distribution within the myocardium showed a slight decrease of the ratio of subendocardial to subepicardial blood flow in the left ventricular free wall in response to exercise, and within the brain there was a relative increase in the blood flow to the cerebellum.


Comparison of supine and sitting body position during a triangular exercise test. I. Experiences in healthy subjects. A comparison of haemodynamic parameters is performed during a triangular exercise test on bicycle ergometer in respect of studying the influence of supine and sitting body position. At the maximal symptom-limited work load reached the heart rate is on the average 9.2% higher, the arterial systolic pressure 16.1% and the cardiac output 17.2% less in the sitting body position (P less than 0.001). On the opposite the pulmonary artery pressure during work is of slightly but not significantly higher level in the sitting position than in the supine. This phenomenon is explained by a prevailing of the beta-adrenergic tonus in our untrained subjects, while total sympathetic stimulation seems to be comparable in both body positions.


Effects of fatiguing isometric and isotonic exercise on resisted and unresisted reaction time components. Fractionated resisted and unresisted RT for a knee-extension task was assessed on 12 male subjects over a 10-day treatment period. The first 4 days were baseline days and were designed to stabilize all RT values as well as strength measures. For the next 6 days the subjects were alternately administered isometric and isotonic exercise designed to fatigue the quadriceps musculature. Although significant strength decrements were manifested for both isometric exercise (57%) and isotonic exercise (35%), no changes were shown in the unresisted fractionated RT components. Conversely all resisted RT changes were manifested in the muscular component suggesting a peripheral site for neuromuscular fatigue.


[Evaluation of changes in pulse rate caused by stimuli (author's transl)]. Short acoustical stimuli induce a biphasic reaction in pulse rate. After an initial increase in frequency, pulse rate decreases below the value calculated before stimulation. This decrease is followed by a slow increase towards the baseline value. As described by other authors the maximum occurs at the 4th heart beat after onset of stimuli. It could be pointed out that the occurrence of the maximum is related to the pulse rate measured before the stimuli. The higher this rate, the "later" the maximum occurs if it is expressed in beats after stimulation. A new mode of evaluation which is independent of pulse rate pointed out that the time between stimulus and maximum is constant. It is proposed to use the evaluation described here in order to allow a most exact location of the extreme values. For experiments with very small variability of pulse rate the evaluation used till now will be sufficient, but only if the mean pulse rate and it's standard deviation before stimulation is mentioned.


A portable heart rate distribution recorder for studying daily physical activity. This paper provides a brief description of a new 8-register heartbeat integrator for recording the heart rate over a long period (24-h or more) in order to assess daily physical activity in children and adults. This compact, rugged device records the cardiac beat to beat interval in seven registers, ranging from 40--225 H4/min. An eight register, the so called "quality level"; (range 225--300 Hr/min) is added to count all non-physiological pulses resulting from muscle noise, etc. To test for validity this system was evaluated simultaneously against two established systems; a manual acoustic monitoring system and a heart rate recording system. Comparison of the results demonstrated good agreement. Integrator influences on the normal daily activity behaviour of the children (age 5 yrs.) was checked with the pedometer method. It was found that wearing of the heartbeat integrator did not appreciably influenced the normal behaviour of the children.


Effect of hyperoxia on performance capacity of firemen. We examined the effect of O2-enriched air upon performance capacity and some physiological and psychological variables. Eight firemen were studied during seven bouts of 2 min treadmill-running while breathing air with 21 or 40% oxygen. The duration of the resting periods between the working bouts was chosed by the subjects themselves, with the instructions to rest as short as possible. Total resting time decreased by 29% and total amount of air used by 6%, under the 40% oxygen condition. There were no differences in 1) minute ventilation during working periods (when the subjects breathed 40% oxygen respiratory rate decreased whereas tidalvolume increased), 2) heart rate reached during working periods, 3) subjective feelings of fatigue as indicated by the subjects at the end of every working period. Advantages of the use of O2-enriched air by firemen are discussed and it is concluded that breathing air with 40% oxygen does not mean an extra physiological or psychological load for the organism. Finally, possible factors that made a subject decide to start again are discussed and the importance of the respiratory rate in this decision is indicated.


Validity and reliability of pedometers in habitual activity research. In 12--18 year old boys actual steprate on a treadmill was compared to the scores of two types of mechanical pedometers (Russian and German), attached to the waist. Both types show deviations from actual steprate in running at speeds of 8 and 10 km - h-1 of ca. 5% (+/- 9%). In walking or running at 6 km - h-1 and in running at 14 km - h-1 both types give an overestimation of ca. 8.5% (+/- 8%). In walking at a speed of 2 and 4 km - h-1 the scores are not reliable because of the big standard deviation of ca. 34%. Oxygen uptake (ml - kg-1) and heart rate (beats - min-1) increase more in running than in walking, actual steprate (steps - min-1) however increases less in running compared to walking. If pedometers register only during running they reflect actual steprate fairly good and give a good estimation of the change in oxygen uptake as speed gathers.


Signal characteristics of EMG during fatigue. Electromyographic (EMG) activity of m. rectus femoris muscle was registered from young male and female subjects during maintained isometric knee extension at 60% of maximal voluntary contraction. The following EMG parameters were analyzed for the entire fatigue time: integrated EMG (IEMG),  averaged motor unit potential (AMUP) and power spectral density function (PSDF). The results indicated a slight but continuous rise of IEMG during the fatigue period. AMUP showed sensitivity to fatigue with increase in amplitude, rise time, and number of spikes counted. PSDF was also easily affected by  fatigue so that the total power density curve was shifted towards lower frequencies with a high frequency decay. The mean power frequency decreased linearily as a function of fatigue time. The findings suggest that in addition to natural recruitment of new motor units the fatigue is characterized by marked reduction in the conduction velocities of action potential along the used muscle fibers.


A comparison of three W170 protocols.

A comparison of three W170 protocols. This study compared the W170 scores of 9 male subjects in kgm/kg X min resultant from the following protocols: 2 X 6 min workloads (3 min rest between each bout), 3 X 4 min workloads (1 1/2 min rest between each bout), and 4 X 3 min workloads (1 min rest between each bout). Each subject experienced 2 preliminary rides in order to overcome the problems of learning and habituation and the order of the 3 experimental treatments was randomly assigned to each subject. An analysis of variance repeated measures design revealed that there was no statistically significant difference between the 3 protocols at the 0.05 level. The scores for the three W170 protocols correlated -0.084, 0.040, and -0.142 with VO2 max in ml/kg X min. The correlation coefficient between actual VO2 max in ml/kg X min and that predicted from the Astrand-Ryhming nomogram was 0.723.


Influence of water temperature on thermal, circulatory and respiratory responses to muscular work. Different muscular exercises have been executed on a bicycle ergometer during immersion in water, the temperature of which varied between 20 and 40 degrees C. During submaximal works, O2 consumption was not modified by the temperature of the water. On the other hand, body temperature (rectal and muscular) are clearly influenced by environment. The temperature of the quadriceps varies from 37.7-38.5 degrees C when the bath temperature rises from 20-40 degrees C during the same work intensity corresponding to 1/3 of the individual maximal work capacity. The rectal temperature was always lower about 0.5 degrees C. Ventilation and heart rate underwent modifications which were significantly accentuated in hot water. Maximal O2 consumption does not reach its highest level in cold water. The low muscular temperature observed in these conditions seems to limit the aerobic metabolism and the working of the muscles. Maximal O2 consumption then rises in parallel with the increase in bath temperature and in body temperatures. In very hot water however (40 degrees C), when rectal temperature rises unduly, the circulatory demand linked to thermolysis becomes excessive, and maximal O2 consumption decreases.


[Behavior of physiological parameters and performance in a compensatory tracking task from the standpoint of aptitude judgements (author's transl)]. Activation behavior and performance were examined in twenty five subjects participated in a compensatory tracking task. The employed physiological parameters were useful for demonstration of interindividual differences in the activation behavior, personality characteristics are considered. Groups were formed according to the level of heart rate, arrhythmia, respiratory rate and level of performance. It was shown that exists a relation between activation level and performance. With regard to the relation between activation and performance may be derived psychophysiological aptitude judgements.


Relationship of triceps surae torques to photographed tibia-calcaneum angles in man (II). A previous paper described an apparatus and method for giving the relationship between triceps surae torque and the tibia-calcaneum angle. As a first approximation we took the angle between the calcaneum and the foot-plate as being invariable in all subjects, when the torque was zero. The aim of the present work is to measure the inter-individual variations of the angle. 1. Guide-marks are selected on the skin; showing the axes of the calcaneum and of the leg. Metal rods indicate the axes thus defined and the true angle between the leg and the calcaneum is measured by photography. The curves drawn from these true angles differ from the preceding curves by 0 degrees to 10 degrees for normal children and +12 degrees to -15 degrees for cerebral palsied children. 2. The photographic method verifies the exactitude of the trigonometrical method of correcting angles that we proposed in the previous paper.


To what extent is the tibia-calcaneum angle a reliable measurement of the triceps surae length? Radiological correction of the torque-angle curve (III). Previous papers gave some methods for the reliable measurement of the tibia-calcaneum angle. It is of common use to evaluate the physical properties of triceps surae on the basis of torque-angle curves. However this method is reliable only if each tibia-calcaneum angle corresponds to a defined distance between the insertions of the muscle in subjects of the same height. Evidence is given by radiological measurements that this correspondance is correct in normal children. However, this is no longer true in certain cerebral palsied children because of abnormal translation of the calcaneum and/or abnormal ratio of bone sizes. In this case the torque-angle curves do not define properly the torque-length curves. A method of correction is given. This correction may be as high as 15 degrees.


The relationship of level of habitual activity to measures of leanness-fatness, physical working capacity, strength and motor ability in 17 and 18 year-old males. The relationships between physical working capacity (PWC), level of habitual activity, relative leanness-fatness, isometric strength and motor ability have been examined in 85 17 and 18 year-old school boys. Level of habitual activity was found to be significantly related to PWC and to the strength and motor ability scores, whilst relative leanness-fatness was not significantly related to any of the other variables studied. Some of the apparent association between PWC and the strength and motor ability scores was due to a common dependence on body size, but the relationship between PWC and four performance variables remained significant when the influence of differences in size of the subjects was removed. It is suggested that differences in the level of habitual activity of post adolescent male school boys influence the physical working capacity but not relative leanness-fatness. The association between level of habitual activity and strength and motor ability scores suggests that the latter variables may possibly influence the level of habitual activity in this type of subject.


Familial trisomy 9p and spinal muscular atrophy: clinical, cytogenetic and embryological findings. The pre- and postnatal clinical, cytogenetic and embryological findings in a family suffering from trisomy 9p and spinal muscular atrophy are presented. The clinical picture of the "trisomy 9p" -syndrome is delineated. Concurrence of autosomal aberration and spinal muscular atrophy, probably of the Werdnig-Hoffmann type, is discussed.


Uric acid infarctions in the kidneys of newborn infants. A study on the changing incidence and on oxypurine ratios. Among 1115 newborns who died during 1957--1976, 136 (12.2%) showed macroscopic renal uric acid infarctions. The incidence depended on the age of the infants and their fluid supply during the first days of life. After introduction of parenteral alkali-glucose infusion in the treatment of perinatal complications, the incidence of renal uric acid infarctions decreased from 19.3% to less than 1.0%. Analysis of the oxypurines in the renal uric acid infarctions of three newborns revealed high percentages of hypoxanthine (31.1%, 21.8% and 11.0%) along with the uric acid. Hypoxanthine ratios above 15% retrospectively point to chronic hypoxia of the newborn.


Use of saliva in monitoring carbamazepine medication in epileptic children. In 17 children on carbamazepine medication alone and 15 children on combined drug regimens, carbamazepine levels were determined in paired samples of serum and mixed saliva by enzyme immunoassay. Carbamazepine levels in serum and saliva were highly correlated in within-patient and between patient series (r = 0.87--0.94). Salivary levels were altered to a minor and clinically insignificant degree by stimulation of saliva flow. Mean saliva/serum ratios, calculated from drug concentrations in saliva specimens collected without and with stimulation were 0.44--0.45 and 0.41--0.43, respectively. The saliva/serum ratio was independent of the serum carbamazepine level and was not affected by concomitant drug medication. The data indicate that measuring salivary levels by enzyme immunoassay is suitable for predicting serum carbamazepine levels. Thus, measurement of carbamazepine levels in mixed saliva samples obtained by a noninvasive technique is recommended for routine monitoring of carbamazepine medication in epileptic children.


Quantitative determination of lactose, maltose, and sucrose in urine. A simple method for determination of lactose, maltose and sucrose in urine is described. The principle of the method consists of enzymatic splitting of these disaccharides and specific measurement the resulting glucose by the Beckman Glucose-Analyzer. The precision and accuracy of the method have been evaluated and its clinical application is briefly discussed.


Serum alkaline phosphatase isoenzymes in childhood. Using a combination of L-phenylalanine inhibition and heat inactivation, the serum alkaline phosphatase (AP)  in 2 to 13 year old children without evidence of hepatobiliary, osseous, or intestinal disease was separated in three fractions; i.e. L-phenylalanine sensitive AP (LPSAP), heat-stable non-L-phenylalanine sensitive AP (heat-stable non-LPSAP) and heat sensitive non-L-phenylalanine sensitive AP (heat-sensitive non-LPSAP). The activities of total AP and the different fractions were measured using optimized test conditions. LPSAP, (mainly intestinal AP), accounts for approximately 12% of the total serum AP activity, heat-stable non-LPSAP (mainly hepatobiliary AP) for approximately 9%, and heat-sensitive non-LPSAP (mainly bone AP) for approximately 77%. To give a better differentiation between bone and liver AP, the percentage ratios of heat-stable non-LPSAP/non-LPSAP (Q value), and heat-stable non-LPSAP/total AP, were determined. Both quotients showed a significant negative correlation with total AP, which has to be taken into account in the interpretation of the results of isoenzyme determinations of serum AP activity. The above semiquantitative separation of AP isoenzymes can be readily done in a routine clinical laboratory.


Congenital adrenal hyperplasia: renin and steroid values during treatment. Plasma renin activity (PRA), aldosterone (Aldo), 17alpha-hydroxyprogesterone (17-OHP) and testosterone (T), together with urine sodium, pregnanetriol, 17-oxosteroids and the 11-oxygenation index (11-OH) were estimated in 23 patients (age 5.7--18 yrs.) with congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency during glucocorticoid treatment. Elevated PRA levels (1400--17200 ng Al/l/hr) were found in 13 out of 15 patients with a history of salt loss. Three non-salt losers showed high PRA levels and in the remaining 5 the levels were in the upper normal range (540--900 ng Al/l/hr). Plasma Aldo levels were normal (25--620 pmol/l) in 18 patients and slightly elevated (690--2360 pmol/l) in 5. While these results indicate persistent impairment of sodium homeostasis in CAH patients, no significant correlations between log. PRA, log. Aldo and urinary sodium excretion were found. Mid-day 17-OHP levels ranged from 9 to 117 nmol/l and T from 0.3 to 18.0 nmol/l. Neither the 17-OHP nor the T results correlated well with the clinical assessment of therapeutic control. The results of the urinary steroid determinations showed better agreement with the clinical assessment of treatment and the 17-oxosteroid, pregnanetriol and 11-OH index results appeared to be better discriminants between good and poor control. Twelve of the patients with a history of early salt loss were reinvestigated after one month's treatment with oral 9 alpha-flurohydrocortisone (0.05 mg/day). PRA was reduced in 7 patients and 17-OHP fell in 10 patients. No consistent changes were found in Aldo, T, or urinary sodium and steroid excretion during this low-dose mineralocorticoid treatment.


A case of progressive external ophthalmoplegia (Kiloh-Nevin type) with abnormal mitochondria. Clinical, histochemical and ultrastructural findings. A case of progressive external ophthalmoplegia is described, in which the onset of the illness was at 28--30 years, with fatigability and muscular pains in the lower limbs as presenting symptoms. At 36--37 years weakness of the mimic muscles also appeared and fatigability and muscular pains spread to the upper limbs: EMG examination showed signs of light myopathic involvement of the shoulder-girdle muscles, so that a muscular biopsy was performed (right deltoid). Histoenzymologic studies showed the presence of generally atrophic dark fibres, which can be brought about to red-ragged fibres. Ultrastructural study showed bizarrely shaped mitochondria, with dense matrix and circular and confluent cristae, which were found in fibres with plenty of indifferent sarcoplasm and with anomalies in myofibrils. No mitochondrial inclusions were seen.


An experimental permeabilization of the blood-brain barrier by electric field application. This work investigates the method of 'transcerebral electrolysis' in rabbits previously used by other authors (e.g. G. Bourguignon). The observation of the animal, with EEG record, and the macroscopic and microscopic studies, have allowed to precise the physical parameters which do not damage the brain functions: current intensity of not more than 5 mA, applied on large electrodes. In this manner, without traumatization of the brain, the blood-brain barrier allows passage of many substances (dyes, tracers, drugs) and this permeability remains for several days.


Cough syncope: the possible relation to hydrocephalus ex vacuo. Pneumoencephalographic data in five male patients with cough syncope were compared to those from age-matched patients with syncope from other causes. The 3rd ventricle width was significantly larger in patients with cough syncope than in the control group (p less than 0.01). Theoretically, the most plausible role of hydrocephalus ex vacuo in cough syncope may be: either it causes increased sensitivity to changes normally encountered during coughing, or--which seems less likely--it may abolish mechanisms normally restraining cough.


Hypotensive effects of sodium volume depletion and 1-sar-8-ala-angiotensin II in relation to plasma renin in hypertensive patients. The hypotensive effect of acute sodium volume depletion, produced by chlorthalidone and a low sodium diet, was inversely related to the plasma renin concentration (PRC) in 13 hypertensive patients of varying aetiology (r = 0.61; p less than 0.05); weight reduction induced by this therapy was not related to PRC (r = 0.12; p greater than 0.1). The angiotensin II antagonist 1-sar-8-ala-angiotensin II failed to reduce arterial pressure when the patients ingested 130 mEq sodium per day, but pressure fell when it was infused during sodium volume depletion, except when PRC remained low; the changes in pressure were related to the plasma renin level (r = 0.78; p less than o.005). The combined hypotensive response to acute sodium volume depletion and to angiotensin II blockade during sodium volume depletion was not related to PRC (r = 0.15; p greater than 0.1). The results demonstrate that acute sodium volume depletion caused similar weight loss in patients with high and low PRC values, and it would have had similar hypotensive effects but for angiotensin-induced vasoconstriction in the high renin patients. Since 1-sar-8-ala-angiotensin II also reduced arterial pressure in 6 patients during chronic diuretic therapy, angiotensin II must still induce vasoconstriction in these circumstances.


Distribution, elimination and effect of furosemide in normal subjects and in patients with heart failure. After furosemide 40 mg i. v. its plasma concentration was significantly higher during an 8-hour period in 6 patients with left sided heart failure than in 8 normal subjects. The plasma clearance was significantly lower in the patients than in the normal subjects--1.23 and 2.34 ml/kg/min, respectively. The apparently smaller volume of distribution in the cardiac patients (0.140 1/kg and 0.181 1/kg, respectively) was not significantly different. In the group of normal subjects, whose ages ranged from 27 to 74 years, no correlation was found between age and either plasma clearance or volume of distribution. In all the patients, the renal clearance of furosemide rose from the first to the second hour after the injection (average +/- SD)--39 +/- 17 and 77 +/- 51 ml/min. In normal subjects, the average values did not change--116 +/- 79 and 117 +/- 54 ml/min. The urinary excretion of furosemide and a metabolite (probably a glucuronide) was measured in 16 individuals. 24-hour urines from all the subjects investigated contained between 20 and 30 mg unchanged furosemide (average 25.2 mg). In addition, between 2.7 and 11.2 mg (average 6.7 mg) furosemide was excreted as the metabolite in five patients who had been treated with furosemide for at least the preceding 6 months. An average of 0.8 +/- 0.8 mg of the metabolite was found in 11 subjects who had not previously been treated with furosemide.


Recording of drug prescriptions in the county of Jämtland, Sweden. I. Methodological aspects. Prescribed drugs dispensed to 13% (17000) of the inhabitants in the county of Jämtland, Sweden, have been continuously recorded since 1970. Individual patients in the investigation are fully identifiable by their identity number as used in Sweden, so patients exposed to a particular drug or group of drugs can be reached subsequently, e. g. for studies of the incidence and nature of side effects. The following information is coded at the local pharmacies: prescribing physician, dispensing pharmacy, year and week of dispensation, name, amount and price of drug, dosage, type of prescription record. In a five year period the drop-out rate has decreased from 9% in 1970 to 4% in 1974. Every year at least one drug is prescribed for approximately 60% of the population. During the five year period 74% of the male and 80% of the female population purchased prescription drugs. The representative nature of the data is discussed, as well as their value in detection of irrational drug usage and ascertaining any particular patient's drug history.


Recording of drug prescriptions in the county of Jämtland, Sweden. II. Drug exposure of pregnant women in relation to course and outcome of pregnancy. Prescription data have been analysed in order to study drug exposure of women before, during and after pregnancy as compared to non-pregnant controls. During full term pregnancy (n = 341) drug exposure increased markedly, mostly due to prescription of drugs such as iron and vitamins. Excluding these drugs, the increase was statistically significant only for one third of the women whose case records revealed some intercurrent disease during pregnancy. Women whose pregnancy ended in a spontaneous abortion (n = 29) did not differ significantly from controls in terms of drug exposure before, during or after pregnancy. In an induced abortion group (n = 60), drug exposure was more pronounced before pregnancy than in the other pregnant patients or controls. On comparing the drug history obtained from delivery records with that obtained in this study it was found that only diuretics and urinary tract chemotherapeutics had been noted fairly consistently in the former records.


Plasma and intracellular kinetics of lithium after oral administration of various lithium salts. Five healthy volunteers were treated orally with lithium carbonate, sulphate, or chloride. There were no significant differences in area under time-concentration curves, half-lives, total body clearance or apparent distribution volumes between the various salts, either in plasma or in the RBC compartment. The carbonate salt did show a higher RBC/plasma distribution ratio than the other salts, which might possibly imply greater therapeutic effectiveness of this salt. Some considerations on the tolerability of various lithium salts are discussed.


The effect of an antacid on the bioavailability of indomethacin. The biovailability of indomethacin from two indomethacin-antacid (aluminum hydroxide magnesium carbonate and magnesium hydroxide) combinations was compared with the bioavailability of oral indomethacin. Relative bioavailability was estimated by three methods: comparison of plasma concentrations at various times, comparison of areas under plasma concentration time curves, and comparison of the amount of drug excreted unchanged in the urine. A double blind three-way crossover study was conducted in twelve healthy volunteers. The combination with the slightly smaller amount of antacid (preparation A) showed significantly decreased bioavailability by all three methods in comparison with indomethacin alone (preparation C). The combination with the larger amount of antacid (preparation B) was also less bioavailable than preparation C. This effect was significantly only for the comparison of areas under curves and not for plasma levels, although the mean plasma levels produced by preparation B at all times were lower than those for preparation C. These findings suggest that aluminum hydroxide magnesium carbonate and magnesium hydroxide decrease the bioavailability of indomethacin.


Dose-dependence of the pharmacokinetics of quinidine. Quinidine was administrated orally to five healthy male volunteers. Doses of 0.2 g t.i.d., 0.3 g t.i.d. and 0.4 g t.i.d. were given for five days with at least four weeks between each test period. The plasma concentration of quinidine was measured before the morning dose on Days 2-5 of treatment, and 1, 2, 4 and 8 h after the morning dose on the 5th day. There was not a linear relationship between the increase in dose and the increase in plasma concentration of quinidine. A dose increase of 50% from 0.6 to 0.9 g quinidine sulphate per day resulted in an increase in steady state concentration of 94%. A further 33% increase in dose, from 0.9 to 1.2 g daily, resulted in a 55% increase in the steady state concentration of quinidine. The results demonstrate dose-dependent pharmacokinetics for quinidine. Possible explanations for the nonlinear pharmacokinetics are discussed.


Genetic control of two different types of antibody responses to oxazolone. The genetic control of antibody responses induced by contact sensitization with oxazolone and immunization with an oxazolone-mouse serum albumin conjugate was studied in inbred, H-2 congenic and nude mice. Both types of antibody responses are T cell-dependent and regulated by immune response genes mapping at the I-B subregion of the H-2 complex. The relative magnitude of antibody responses induced by the two methods of immunization is governed by a gene or genes mapping at the I-B subregion of the H-2 complex. Presentation of antigen by these two methods gives H-2-dependent distributions of high and low responsiveness which are exactly opposite. Non-H-2 genes affect the overall level of antibody response but not the relative magnitude of the responses.


Study of two different subpopulations of anti-acetylcholine receptor antibodies in a rabbit with experimental auto-immune myasthenia gravis. Two different subpopulations of anti-acetylcholine receptor antibodies were studied during the evolution of experimental autoimmune myasthenia in one rabbit immunized with Torpedo acetylcholine receptor. The results show that the subpopulation of antibodies directed against the toxin-binding site of the receptor might play a role in the appearance of the paralysis observed in this particular case.


Genetic variation in antibody response and natural killer cell activity against a Moloney virus-induced lymphoma (YAC). Antibody formation against the Moloney virus-determined surface antigen (MCSA) was found to be under genetic control. In the (A X C57BL)F1 cross one dominant gene played a major role, resulting in bimodal distribution of the antibody response. This gene showed no linkage to H-2, IgG heavy chain immunoglobulin allotype, the coat color markers B and C, and five different isozyme markers representing chromosome numbers 1, 4, 7, 8 and 9. Antibody response to MCSA was not correlated with antibody titers against the virion proteins, confirming that MCSA was an independent entity. There was no relationship between the segregation of natural killer cell activity and antibody response in a [(A X C57BL) X A] backcross population.


Rat bile as a convenient source of secretory IgA and free secretory component. Rat hepatic bile contains three proteins as major constituents: secretory IgA (SIgA), free secretory component (FSC) and albumin. Traces of alpha-macroglobulin, transferrin, IgG and IgM are also detectable. The bile duct daily pours between 5-12 mg each of SIgA and FSC into the rat duodenum. The origin and function of these proteins in bile may represent important clues in the understanding of the SIgA system.


Differential effect of various 6-hydroxydopa treatments on the development of central and peripheral noradrenergic neurons. 6-Hydroxydopamine or 6-hydroxydopa injected systemically into newborn rats produced marked changes in the development of central and peripheral noradrenergic neurons. Noradrenaline concentration was elevated in the brain stem, particularly in the pons, and decreased in the cerebral cortex and the spinal cord while in the cerebellum, the effects were dependent on the mode of administration. The changes produced by 6-hydroxydopa in brain regional noradrenaline were related to the dose injected at birth. Similar modifications in the development of central noradrenergic neurons were found in the offspring of rats which had received 6-hydroxydopa at 16 days of gestation. The involvement of peripheral sympathetic neurons varied with the compound used and the form of its administration. Thus, 6-hydroxydopamine produced a permanent although partial peripheral sympathectomy, an effect which was less evident following multiple injections of 6-hydroxydopa after birth and almost minimal after a single injection. The prenatal administration of 6-hydroxydopa did not alter peripheral sympathetic neurons. It is concluded that with the appropriate treatment schedule, it is possible to lesion selectively the noradrenergic neurons in the central nervous system.


Effects of the phenothiazine analog, EN-313, on ventricular arrhythmias in the dog. Effects of the phenothiazine analog, EN-313, on ventricular electrical activity were studied using isolated blood-superfused canine Purkinje fibers and conscious dogs with sustained ventricular arrhythmias following a 2-stage ligation of the left anterior descending coronary artery, EN-313, less than 3 mg/kg, i.v., had no significant effect on transmembrane potentials of Purkinje fibers. At 3 mg/kg, EN-313 significantly decreased maximum upstroke velocity of phase 0 depolarization and action potential duration. In conscious dogs, EN-313 (1-3 mg/kg i.v.; 10-20 mg/kg p.o.) reduced arrhythmias that occured larger than or equal to 24 h after coronary artery ligation. No excessive changes in electrocardiographic parameters were observed following EN-313. These studies demonstrate that EN-313 suppresses ventricular arrhythmias in doses which have little effect on cellular electrophysiologic properties of normal Purkinje fibers and suggest that EN-313 should be useful in treating cardiac arrhythmias arising as a result of coronary occlusion.


Time-response curves for barium and noradrenaline in vas deferens of castrated rat. Time-response curves for barium chloride and noradrenaline were obtained in the isolated vas deferens of 30-day castrated rats. The contractions induced by a maximal dose of barium chloride reached a peak after about 20-30 sec and then decreased to a lower level (fade). 5 min after drug addition the response had faded to about 20% of the peak contraction while in normal preparations it decreased to about 55%. When calcium was removed from the nutrient solution, both peak and 5-min effects of sequential doses were reduced, and fell progressively at a faster rate than in normal preparations. When Ca2+ concentration was increased from 1.8 mM up to 36.0 mM, fading was abolished. The data were analyzed on the basis of receptor changes involving the translocation of calcium in smooth muscle.


Effect of anticonvulsants on seizures developing in the course of daily administration of pentetrazol to rats. Progressive behavioral and electroencephalographic (EEG) changes were examined following daily administration of pentetrazol (PTZ) to rats. A dose (40 mg/kg/day i.p.) of PTZ which, on the first day, induced clonic convulsions with spike and wave complexes, over several days progressively increased its effect and finally induced 'violent convulsions' with EEG seizures of high frequency components. In rats showing these violent convulsions, the PTZ convulsive threshold was decreased and, even after a 4- to 10-month resting period, the violent convulsion was elicited with the same dose of PTZ. Trimethadione and phenobarbital in doses blocking clonic convulsion in normal rats, did not suppress these violent convulsions. Higher doses of the two drugs were necessary to suppress the violent convulsion. Diphenylhydantoin did not suppress either type of convulsions. It is suggested that the progressive development of seizure by PTZ is a kindling effect and that a part of the neuronal mechanisms by which the violent convulsion occurs is involved in the mechanisms underlying the clonic convulsion.


Effect of bradykinin on the renal medullary osmotic gradient in water diuresis. The effect of bradykinin on the renal medullary osmotic gradient was evaluated in anesthetized dogs which were undergoing water diuresis and which received a unilateral renal arterial infusion of bradykinin. The effect of the peptide on the medullary osmotic gradient was determined by analysis of medullary tissue electrolyte and urea concentrations and by analysis of changes in urine osmolality induced by vasopressin. Bradykinin decreased the total osmolality per kg H2O in tissue from inner medulla and papilla (-18.7 +/- 6% and -19.3 +/- 8%) and increased fractional water excretion (3.8 +/- 1.3%). Furthermore, a direct relationship between changes in free water clearance and changes in papillary tissue, osmolality was found. Finally, the increase in urine osmolality after ADH was significantly less in vasodilated than in control kidneys. These results indicate that bradykinin can diminish the medullary osmotic gradient during water diuresis in the dog. Thus, a bradykinin-induced increase in free water clearance may be accounted for by other than an inhibition of proximal tubular sodium reabsorption.


Antiarrhythmic and electrophysiological effects of CH-200. A new antiarrhythmic drug CH-200, 5-phenacyl-thieno[3,2-c]yridinium, was compared with procainamide and lidocaine in a two-stage coronary ligation arrhythmia model for its efficacy and electrophysiological properties. CH-200 suppressed arrhythmia in beagle dogs more effectively than did procainamide and lidocaine. The antiarrhythmic effects of CH-200 and procainamide developed slowly and lasted longer than those of lidocaine. Electrophysiological studies with CH-200 showed that it decreased max dV/dt of the action potential. This effect was dependent on the heart rate: the higher the rate, the stronger the effect. CH-200, procainamide and lidocaine prolonged the effective refractory period and this effect seemed to be responsible for suppressing the arrhythmia after coronary ligation. CH-200 and procainamide increased the frequency of ventricular pacemaker activity, while lidocaine decreased it. These effects appear to be unimportant for the antiarrhythmic effects.


Some possibilities for prostaglandin mediation in the contractile response to ATP of the guinea-pig digestive tract. Several contractile responses of longitudinal muscles of the guinea-pig digestive tract to exogenously applied ATP (10-300 micrometer), including "rebound" contractions, were inhibited by indomethacin (3-20 micrometer) or polyphloretin phosphate (10-100 microgram/ml). Relaxations to ATP  in stomach and large intestinal muscles were increased by these drugs. Prostaglandin release might therefore contribute to the contractile responses of the guinea-pig digestive tract to ATP.


The interaction of erythropoietin with fetal liver cells. II. Inhibition of the erythropoietin effect by interferon. To investigate the effect of interferon on the proliferation of normal erythroid precursor cells, various interferon preparations were added to mouse fetal liver cells cultured in a liquid microculture system. The effect of interferon was studied using cellular tritiated thymidine incorporation both in the presence and in the absence of erythropoietin. Interferon was found to suppress cellular tritiated thymidine incorporation. The suppression was directly related to the antiviral activity and was not found when control preparations were used. The mechanism of suppression seemed to involve a direct effect on the cells which was dependent of erythropoietin. These studies suggest that the viral inhibitory effects of interferon may also be accompanied by effects on normal cellular proliferation.


Effects of fibroblasts on the growth of erythroid progenitor cells in vitro. The effect of embryo fibroblasts on the growth of erythroid colony-forming cells in vitro (CFU-e) from mouse bone marrow was investigated. First, the maintenance of CFU-e number in suspension culture was assayed. CFU-e recovered from suspension culture fell rapidly to values below 30% of the initial number. When erythropoietin (EP) was added, the initial decline during the first day was followed by a rise to 80%. In cultures supplemented with irradiated fibroblasts, the number of CFU-e did not show an abortive fall, but there was a slight increase during 3 days of culturing. The influence of fibroblasts on the colony-forming ability of CFU-e was studied in a semisolid culture system composed of an agar underlayer and a methylcellulose overlayer. The number of erythroid colonies scored after 5 days of culture in the presence of different levels of EP was proportional to the number of added fibroblasts and the colony size (depending on the number of fibroblasts) increased to macroscopic dimensions. Fibroblasts alone, without EP, induced colony formation by CFU-e if added in concentrations of 1 X 10(5) or higher. EP was not detectable in medium conditioned by the fibroblasts. These data indicate that fibroblasts may stimulate erythroid colony formation (in the absence of EP) and enhance the colony-forming ability of CFU-e in the presence of EP. From these results, it is suggested that fibroblasts exert proliferation activating effects on CFU-e target cells.


Factors regulating yolk sac hematopoiesis in diffusion chambers: various types of sera, cyclophosphamide, irradiation and long-term culture. A series of studies were conducted using suspensions of murine 10 1/2 day yolk sac cells, cultured in diffusion chambers (DC), to evaluate the effects of several variables on cell growth and differentiation. The variables evaluated were: treatment of chamber recipients with cyclophosphamide (Cy) or sublethal total body irradiation (TBI), culture medium supplementation with different sera, and long-term culture. The growth of cells in Cy- and TBI-groups was parallel to that of the control group (C) until day 7 of culture. Thereafter, cells in the chambers of each group proliferated at a different rate. Whereas, cell growth in Cy-hosts was significantly greater than in C-hosts, growth of TBI-hosts was less than that in C-hosts. Horse serum supported chamber cellularity better than syngeneic mouse serum or fetal calf serum. Long-term cultures showed an increase in cell numbers until day 56, followed by a steady decrease to day 70, reaching a new level that was maintained until day 98. By day 14 of culture, and throughout the long-term culture study, there was no difference in the pattern of differentiation of DC cultured yolk sac cells. Regardless of the type of host treatment or culture medium the cells harvested were macrophages, plasma cells and lymphocytes.


Hydroxyurea (HU) in experimental hematology. I. Characterization of in vitro and in vivo effects on progenitor and transit cells. The lethal effect of hydroxyurea (HU) on normal and regenerating mouse bone marrow was examined in vivo and in vitro. Progenitor cells (DCPC) were assayed by their capacity to form granulocytes and macrophages in 7-day diffusion chamber (DC) cultures. Dose-response experiments showed that a plateau effect was obtained in vitro for HU concentrations above 1 mM, killing about 40% of regenerating progenitor cells or normal proliferative granulocytes. Similarly, a plateau effect was found for doses exceeding about 15 mg i.p., when lethal effects on 3-4 day DC cultures were measured. Time-response studies in vitro showed that about 60% of maximum killing was achieved after only 10 min, with a levelling off of the effect for exposure times between 1 and 3 h. Total depression of 3H-thymidine incorporation in DC cultures was achieved in less than 0.5 h, and subsided within 4-6 h, after one i.p. injection of 23 mg HU. HU had no appreciable effect on DCPC of adult normal marrow, but killed 15% of agar colony-forming cells.


Hydroxyurea (HU) in experimental hematology. II. Similarities and dissimilarities between HU and 3H-thymidine killing. The lethal effects of hydroxyurea (HU) and 3H-thymidine (3H-dT) on mouse hematopoietic cells were compared after various experimental procedures. The aim was to explore the relative efficiency of these two methods in analyzing the kinetic properties of progenitor cells. Both methods indicated that 40-50% of progenitor cells assayed with diffusion chamber culture (DCPC) were in S phase 3 days after cyclophosphamide treatment. Effects of HU, but not 3H-dT, were altered by neostigmine triggering of normal DCPC into cell cycle. On the other hand, cooling marrow cells before exposure to HU or 3H-dT largely abrogated the effect of HU, but not of 3H-dT. Blood-borne DCPC were not in cycle according to the HU effect. Separated blood DCPC were apparently in cycle, as judged with 3H-dT, but the Isopaque-Ficoll separation procedure rendered normal marrow DCPC susceptible to 3H-dT killing. When marrow cells were cultured in DC the HU technique appeared to be suitable for evaluation of modulation of progenitor cell (CFU-S or CFU-C) proliferation, whereas our previous experiments have shown that the 3H-dT technique is a convenient method to assess the initial triggering of CFU-S into cycle in DC culture.


In vivo synchronization of haemopoietic stem cells with hydroxyurea. Four injections of hydroxyurea 1 mg/g body weight, given to normal mice 31, 24, 10 and 7 h before sampling bone marrow, reduced CFU-S content of femoral marrow to 30% of normal in Balb/c female and to 10% of normal in C57 B1 male mice. Over 80% of the surviving CFU-S were in the S phase of cycle, as judged from their sensitivity to killing by hydroxyurea or ARA-C.


Pulse cytophotometric investigations concerning ploidy and proliferation pattern of invasive squamous cell carcinomas of the cervix uteri. Tumor cell suspensions from 100 biopsies of squamous cell carcinomas of the cervix uteri were investigated by impulse cytophotometry (ICP) after staining with pepsin-ethidium bromide. We estimated the ploidy pattern by comparing the ICP curves with normal diploid material. The originally linearly classified curves were transformed in a logarithmical manner. We found 48 diploid populations and 42 polyploid populations, among them 19 tetraploid tumors. In these the 4c-peak was the highest. In 10 cases there were aneuploid stem lines, mainly lying between 2c and 4c; 2 curves had a hypertetraploid pattern. Helpful for interpretation of the whole curve is the introduction of an index: the "relative mean DNA-content" (DNA). In 15 diploid tumors we found a low proliferating rate, characterized by low 4c-peaks. For interpretation of polyploid cell cycles a completed nomenclature of cell cycle phases was introduced. Comparing our material with chromosome analyses in laterature we found more polyploid, e.g. tetraploid tumors. It can be assumed that the estimation of ploidy pattern solely by DNA measurements has another meaning than by chromosome analyses. The higher ploid peaks in DNA distribution curves (e.g. ICP-karyograms) represent not only true polyploid nuclei but also nuclei which are in a blocked premitotic resting phase (G2 for 4c; G'2 for 8c and so on). The ICP is a valuable method for estimating biological pecularities of tumor cell suspensions.


Prevention of 2-acetylaminofluorene-induced extrahepatic short-term effects by 3-methylcholanthrene. It is well known that simultaneous application of polycyclic carcinogenic hydrocarbons, especially 3-methylcholanthrene (MC) inhibits or prevents tumorigenesis induced by carcinogenic aromatic amines or azo dyes. Short-term tests showed a mitogenic effect upon adrenal cortex 48 hours following a single dose of 2-acetylaminofluorene (AAF) among other carcinogenic substances. 6 mg/kg body weight given simultaneously prevent the proliferative response of the adrenals by AAF (60 mg/kg b.w.) in male Sprague-Dawley rats. These different effects can be assumed to depend on the production of carcinogenic derivatives or their non-production. Therefore, the positive adrenal reaction by other substances tested is probably also provoked by carcinogenic compounds. The lack of responsiveness by MC may reflect a fundamental change of AAF metabolism. The mode of action is unknown. Possible explanations are discussed.


[Studies on the cytotoxicity of poly-L-arginine, poly-L-lysine and DEAE-dextran in L-cells and mouse embryonic fibroblasts]. Cellular insulin uptake is influenced by poly-L-arginine, poly-L-lysine and DEAE-dextran. In this study it is asked for the mechanisms of these influences as well as for the cytotoxicity of different concentrations of these substances. The experiments aim to contribute to the knowledge on toxic concentrations of polycations.


Scanning electron microscopic studies on untreated and transformed mouse embryo fibroblast cell cultures. Cultures of CBA T6T6 mouse embryo cells were transformed by 20-methylcholanthrene (MC) treatment in vitro. Untreated and MC treated cells and reexplanted cells of tumours originating from MC treated cells were compared by scanning electron microscopy (SEM). The 3 cultures showed considerable differences in the situation of the cells compared to each other, as well as in the number and shape of the surface formations.