Multifactorial index of cardiac risk in noncardiac surgical procedures. To determine which preoperative factors might affect the development of cardiac complications after major noncardiac operations, we prospectively studied 1001 patients over 40 years of age. By multivariate discriminant analysis, we identified nine independent significant correlates of life-threatening and fatal cardiac complications: preoperative third heart sound or jugular venous distention; myocardial infarction in the preceding six months; more than five premature ventricular contractions per minute documented at any time before operation; rhythm other than sinus or presence of premature atrial contractions on preoperative electrocardiogram; age over 70 years; intraperitoneal, intrathoracic or aortic operation; emergency operation; important valvular aortic stenosis; and poor general medical condition. Patients could be separated into four classes of significantly different risk. Ten of the 19 postoperative cardiac fatalities occurred in the 18 patients at highest risk. If validated by prospective application, the multifactorial index may allow preoperative estimation of cardiac risk independent of direct surgical risk.


In vitro cell-mediated immunity of cerebrospinal-fluid lymphocytes to myelin basic protein in primary demyelinating diseases. In an attempt to characterize the immunologic reactivity of cerebrospinal-fluid lymphocytes in demyelinating diseases, we compared the myelin-basic-protein-induced in vitro responses of these cells to peripheral blood lymphocytes from the same subjects with a variety of neurologic diseases. Peripheral blood lymphocytes from patients with acute disseminated encephalomyelitis and progressive multiple sclerosis had increased reactivity as compared to those of normal volunteers (P less than 0.01 and P less than 0.05, respectively). Cerebrospinal-fluid lymphocytes from patients with acute disseminated encephalomyelitis and acute and progressive (but not stable) multiple sclerosis were more reactive than cells from subjects with other neurologic diseases (P less than 0.005, P less than 0.02 and P less than 0.05, respectively). Cerebrospinal-fluid lymphocytes manifested a greater reactivity than peripheral blood lymphocytes in acute and progressive multiple sclerosis but not in acute disseminated encephalomyelitis. These findings demonstrate that lymphocytic cells reactive to myelin basic protein are present in the spinal fluid during active demyelinating disease; and that these cells may be more reactive than peripheral blood lymphocytes.


Effect of hypophosphatemia on myocardial performance in man. Severe hypophosphatemia is associated in man with low intracellular stores of ATP and a set of specific cellular dysfunctions. To investigate whether hypophosphatemia affects myocardial performance, we measured cardiac output by thermodilution and calculated stroke work in seven patients with severe hypophosphatemia before, during and after repletion with an intravenous potassium phosphate solution. Mean left ventricular stroke work for these patients increased from 49.57 to 71.71 g-m per beat (P less than 0.01) at the same or higher afterload whereas pulmonary-artery wedge pressure fell from a mean value of 10.1 to 6.7 torr (P less than 0.02). Return of serum phosphate to normal, therefore, improved myocardial stroke work independently of the Starling effect. The mechanism of this improvement in contractile force is unknown but may be related to intracellular availability of ATP.


Structure of a dinucleoside phosphate--drug complex as model for nucleic acid--drug interaction. The crystal structure of a 3:2 complex of the frameshift mutagen proflavine with the dinucleoside phosphate cytidylyl-3'5'-guanosine has been determined. The complex has one drug molecule intercalated between Watson--Crick base pairs of the nucleotide duplex. The other two proflavine molecules are bound to the exterior of the miniature double helix. The orientation of the base pairs in this miniature double helix has aspects similar to that found in RNA 11.


Orientation of cell-surface antigens in the lipid bilayer of lymphocyte plasma membrane. Human HLA-A, B, C and Ia antigens were labelled by lactoperoxidase-catalysed iodination of the inner surface of lymphocyte plasma membrane and thus are transmembrane proteins. In contrast, membrane-bound human IgM and mouse IgM, IgD and Thy-1 antigen were not labelled on the inner membrane surface.


Femoral vasodilatation produced by piribedil (ET495) and its metabolite S584 in the hindleg of the dog. On local injection into the innervated hindleg of the dog piribedil, like apomorphine, produced a vasodilatation blocked by haloperidol. S584, the catechol metabolite of piribedil, produced a vasodilatation which was not blocked by haloperidol. Neither propranolol nor atropine influenced the vasodilatation produced by piribedil or S584. Denervation of the hindleg abolished the responses to piribedil and S584. During the infusion of noradrenaline into the denervated hindleg, the responses to S584 reappeared but those to piribedil did not. It is concluded from these experiments that the vasodilatation produced by piribedil in the innervated hindleg of the dog, like that of apomorphine, is mediated by dopamine receptors and that the effect of piribedil cannot be explained by the formation of its catechol metabolite S584.


The effect of intracerebroventricularly administered GABA on brain monoamine metabolism. Intracerebroventricular injection of gamma-aminobutyric acid (GABA) was performed in male rats and the brain monoamines, 5-hydroxyindoleacetic acid (5-HIAA), tyrosine and tryptophan levels were measured. GABA induced within 30 min a marked dose-dependent increase in the brain contents of dopamine (DA), serotonin (5-HT), tyrosine and tryptophan, while noradrenaline (NA) was lowered. Large doses of GABA, i.e. 1.5-3 mg/rat, were required for these effects. Aminooxyacetic acid (AOAA), an inhibitor of GABA-transaminase, when given alone in a dose of 25 mg/kg i.p. caused a significant rise of DA, 5-HT and tryptophan. The combination of GABA and AOAA raised these levels more than either agent alone. Picrotoxin (4 mg/kg, i.p.) a claimed GABA receptor antagonist partially counteracted the GABA-induced DA rise. Monoamine synthesis was studied in different parts of the brain by measuring the accumulated dopa and 5-hydroxytryptophan (5-HTP), 30 min after NSD 1015 (3-hydroxybenzylhydrazine HCl, 100 mg/kg) an inhibitor of aromatic L-amino-acid decarboxylase, given i.p. 5 min after GABA. GABA caused a marked rise in dopa formation both in DA- and NA-predominated brain regions. Also 5-HTP formation was enhanced. The effects on both dopa and 5-HTP formation showed marked regional differences. The data suggest that GABA, by activating specific receptors, causes inhibition of firing of dopaminergic neurones and the opposite effect on the noradrenergic neurones. The nature of the effect on 5-HT metabolism needs further investigation.


The effect of intraperitoneally administered GABA on brain monoamine metabolism. GABA was injected intraperitoneally to rats in single doses of 2.5 to 1500 mg/kg. Thirty minutes after injection a dose-dependent increase in dopamine (DA) and a decrease in noradrenaline (NA) content were observed in the brain. However, in the lowest dose range these levels showed small but significant changes in the opposite direction. The accumulation of dopa after inhibition of the aromatic L-aminoacid decarboxylase was enhanced by i.p. GABA both in DA- and in NA-predominated brain regions, the dose-response relations being complex. Increased levels of serotonin (5-HT), 5-hydroxyindoleacetic acid (5-HIAA) and tryptophan as well as enhanced accumulation of 5-hydroxytryptophan, induced by decarboxylase inhibition were also observed. The general pattern of effects was similar to that previously observed after intracerebroventricular injection of GABA, although the intraperitoneal doses required were higher. It is suggested that a certain penetration of GABA from the blood into the brain can occur, leading to changes in the physiological activity of monoaminergic neurons.


Haemodynamic and coronary actions of ouabain during coronary infusion. The investigations were carried out on 24 mongrel dogs which were anaesthetized with chloralose or sodium pentobarbital. Ouabain was added to the coronary blood (50, 100 and 200 ng/ml coronary blood or 0.7, 1.4 and 2.8 X 10(-7) M) over periods of 30 or 60 min by intracoronary infusion of the glycoside. Under chloralose anaesthesia, ouabain at concentrations of 100 and 200 ng/ml coronary blood augmented left ventricular dp/dt significantly. No significant changes were observed in coronary resting flow and flow per beat at the same time. Likewise, the maximum reactive hyperaemic blood flow remained constant, indicating the absence of any changes in the tone of the large extramural arteries. Under sodium pentobarbital anaesthesia small decreases in heart rate and increases in left ventricular dp/dt were seen only at the highest ouabain concentration (200 ng/ml). All flow parameters remained unchanged. These experiments provide evidence that concentrations of ouabain which 100- and 200-fold exceed therapeutic maintenance levels and 10- and 20-fold exceed the concentrations that produce constriction of helically cut pig and rabbit coronary arteries in vitro, do not diminish the coronary blood supply of the anaesthetized dog in vivo.


The function of prostaglandins in transmucosal water movement and blood flow in the rat jejunum. 1. Jejunal loops of anaesthetized rats were perfused with isotonic buffer containing PGE1, PGF2alpha or indomethacin. Intestinal blood flow, absorption and secretion of tritiated water were measured. 2. PGE1 at the low concentration of 0.1 microgram ml-1 did not influence intestinal blood flow but increased secretion and decreased absorption of tritiated water. In higher concentrations (0.5 and 6.5 microgram ml-1), blood flow, secretion and absorption were enhanced. 3. PGF2alpha, even in the high concentration of 50 microgram ml-1, did not influence intestinal blood flow but enhanced secretion and decreased absorption of tritiated water. 4. Indomethacin (1 microgram ml-1) decreased intestinal blood flow and secretion but enhanced absorption of tritiated water. 5. The effects of indomethacin on blood flow can be prevented and those on secretion can be even reversed by an additional infusion of PGE1 (0.5 microgram ml-1). 6. PGs appear to play a physiological role in the regulation of intestinal blood flow and transmucosal water movement, since inhibition of endogenous PG synthesis by indomethacin results in effects opposite to those of intraluminally applied PGE1. The results obtained with the low concentration of PGE1 (0.1 microgram ml-1) and with PGF2alpha (50 microgram ml-1) strongly indicate that intestinal water movement can be changed independently of intestinal blood flow.


[Characteristics of inhibition in the receptive fields of the cat visual cortex]. The responses of visual cells in the 17th cortical area to stimulation with bright strips of various width were studied in immobilized cats. The impulse activity was counted in successive time intervals from the beginning of the stimulation and plotted as a function of the stimulus area. Significant differences in time course of the inhibitory process were found between the cortical and geniculate levels. The lag of inhibition behind excitation was much smaller in the cortex than in the geniculate body. Similar data were obtained from cortical response elicited by simultaneous or successive application of two bright strips, one in the excitatory centre and the second in the inhibitory zone of the receptive field. If both strips were placed in the excitatory zone of the field, inhibition depended on the order of illumination of the strips. When this order coincided with the direction in which a moving stimulus had a maximal effect, a large facilitation of the response to the second stimulus was obtained. When the order of presentation was reversed, a strong inhibition appeared. This selectivity of the inhibitory mechanism was attenuated at the periphery of the field where any succession of the stimuli elicited an inhibitory effect.


[Electrophysiologic analysis of cortico-pontine relationships]. Projections of different regions of orbitofrontal and basotemporal cortex as well as of the hippocampus in the pons varolii area were studied by means of focal recording in acute experiments on cats anesthetized with nembutal and chloralose. It is shown that different formations of the frontobasal regions of the neocortex have local projections into the rostral zones of pons varolii and relatively diffuse projections into its caudal regions. The representation of the hippocampus is weaker as compared with the representation of the frontobasal region, and the focal responses are more diffuse. All the studied structures are represented in the nuclei of the pons varolii. The region of the orbitofrontal cortex is not represented in the caudal part of the reticular formation, the basotemporal cortex has no projections into brachium pontis.


[Conditions for development of off-responses to photic stimulation among cat senso-motor neurons]. On- and off-responses to a prolonged optical stimulus (up to 1000 ms) were studied in the cat sensomotor cortex. Similarity of the minimum time of stimulation resulting in the off-response with the cycle of the functional restoration after a single flash was observed. It is suggested that IPSP arising in the cortical neurons form a basis of these time intervals. The influence of stimuli of other modalities (cutaneous) on the off-responses is shown. This influence was observed in the case when the cortical neuron produced an impulse discharge to the cutaneous stimulus.


[Analysis of the background activity of cat caudate nucleus neurons]. Background activity recorded extracellularly from the caudate nucleus neurons was analyzed in immobilized cats. Experimental data processing included the plotting of average frequency curves, interspike interval histograms, intensity functions, correlograms and association histograms. The frequency of the background activity in different caudate neurons varied from 0.5 to 20 imp/s and could change in the same neuron in different time intervals. According to the time structure and statistical parameters the background activity of the caudate neurons was classified in two types: unitary and group. Transformation from one type to the other could be observed in the same neuron. The obtained data do not allow considering the background activity of the caudate neurons as simple random pulse trains.


[Projections of the posterior region of the hypothalamus into its medial, anterior and lateral region]. Effect of stimulation of the lateral and medial supramammillary areas of the hypothalamus was studied in acute experiments on rabbits. The firing of neurons was recorded in the anterior, lateral, dorsal medial and ventral medial hypothalamic areas. Single pulse stimulation of the medial area of the posterior hypothalamus caused changes in discharge rate for 44% of neurons and the stimulation of the lateral area for 35% of the examined neurons. Repetitive stimulation resulted in changes of the discharge rate in 57% of neurons during stimulation of the lateral and in 74% of the medial supramammillary area. Most neurons responded by excitation. The data obtained are discussed from the view point of the role of posterior hypothalamus in the regulation of the adenohypophysis functions.


[Recurrent inhibition of the sympathetic pregnaglionic neurons of the lateral horns of the spinal cord]. 32.5% of the lateral horn sympathetic preganglionic neurons (B2-SPN) recorded in T3, T8-9 and L2 spinal segments of anaesthetized and immobilized cats were able to respond antidromically to repeated stimuli with time interval (16 ms and more) considerably exceeding the refractoriness of these neurons. This effect was not associated with axonal subnormality. A prolonged time interval between antidromic discharges correlated with the ability of orthodromic spikes to inhibit the generation of antidromic discharges throughout the same period which was substantially longer than the possible collision time. Preceding antidromic activation of a fraction of the described neurons partly inhibited the responses of other neurons in this segment elicited by stimulation of segmental nerves or spinal descending pathways. These data indicate that certain lateral horn sympathetic preganglionic neurons have a recurrent inhibitory mechanism.


[Insect interneurons sensitive to polarized light]. Neurons responding with a rhythmic discharge to rotation of a polarization plane (frequency being 0.7 Hz) were found in the optic lobe of scarabaeids Geotrupes. Responses to a polarized light stimulus were compared with those evoked by light intensity modulation and with suspected responses to apparent rotatory movement of a filter. The polarization sensitivity of some observed neurons was about 2. The on-component of the response to polarization coincided with the horizontal position of the electric vector.


[Membrane potential clamping in the horizontal cells of the fish retina]. The membrane potential of horizontal cells was clamped using uniform polarization of a layer of these cells by means of current passed via extracellular electrodes. It is shown that the voltage-current relationship of the nonsynaptic membrane of horizontal cells has in some cases sections with a negative slope. With fast shifts in the clamped potential level the changes in the membrane resistance are completed less than for 20 ms. Comparison of responses to light stimulation recorded with potential clamp and without it showed that participation of the nonsynaptic membrane in generation of responses to light stimulation can change significantly the form of the latter.


[Mechanisms of prolonged action potential generation in barium solutions]. The membrane currents were recorded under voltage clamp from identified nerve cells of the Helix pomatia. The replacement of the external Ca ions in normal solution by Ba ions produced a shift in the potassium conduction-voltage curve along the voltage axis in the positive direction. The decrease in the limiting value of the potassium conduction was also observed. In Na-Ca-free solutions containing Na ions but no other divalent cations the inward membrane current was recorded. This current was separated into two components: an early fast inactivating (I) and a smaller long lasting component (II). It seems that the prolongation of the action potential in barium solution is due to the suppression of K conduction by Ba ions and to the existence of the long-lasting inward current.


A new substance effective against transplantable tumors in vivo: L-cystine-bis-(N,N-beta-chloroethyl)-hydrazide. It is shown that L-cystine-bis-(N,N-beta-chloroethyl)-hydrazide-hydro-bromide possesses strong (50-100%) inhibitory effect in vivo against myeloma P-8, carcinosarcoma Walker, lymphosarcoma Pliss, sarcoma Yoshida, sarcoma Jensen and sarcoma 180 in doses 5-12 mg/kg/day. No suppression of the growth of Ehrlich ascites tumor was observed. The acute toxicity (LD50) of this substance on mice and rats is 71 mg/kg and 47 mg/kg respectively.


Cardio-toxicity of Daunomycin and Adriamycin. Our aim was to check the possibility of modifying the cardio-toxicity of Daunomycin and Adriamycin on guinea pig atria in vitro, through a reduction of calcium concentration in the medium. In a first series of tests, left and right atria still beating were put in a bath containing Tyrode solution. In order to test the influence of hypocalcic conditions on the negative inotropic effects of the two drugs. Tyrode solution contained either the usual amount of calcium or only 50% of it. In a second series of experiments isolated tissues were electrically stimulated in Krebs-bicarbonate solution. In order to avoid the spontaneous activity of the preparations, only isolated left atria were used. Again the medium contained either the normal quantity of calcium or only 50%. The reduction of calcium concentration in the medium results in a statistically significant potentiation of the negative inotropic activity of the two drugs.


VM 26 (4-demethyl-epipodophyllotoxin-beta-d-thenylidine glucoside) in the treatment of urinary bladder tumors. VM 26, a semisynthetic podophyllin derivative (4-demethyl-epipodo-phyllotoxin-beta-d-thenylidine glucoside) has been tested in 67 patients with urinary bladder tumors. In 25 patients with stage T 1 significant prolongation of the disease-free interval was reached. In 25 cases with state T 3-4, the effect of VM 26 was not favorable.


Combination of regional chemotherapy and mastectomy in the treatment of carcinoma of the breast. Five-year results. Thirty-six women with cancer of the breast were treated with infusion of cytotoxic drugs into the first portion of the subclavian artery adjuvant to radical or simple mastectomy. The patients were followed up for five years and the results were compared with a matched group of patients treated by mastectomy alone.  There was no difference between the two groups in the overall mortality at the end of the fith year. The survival rates of patients with stage 3 carcinoma receiving adjuvant chemotherapy were in the first three years significantly better than those of the controls. No impairment of the wound healing was observed and the systemic side effects of the cytotoxic drugs were unimportant. In two patients serious neurologic complications developed and one patient died of pulmonary abscess.


Spermatic vein phlebography in patients with testicular tumors. The performance of funicular lymphography and spermatic vein phlebography during orchiectomy in patients with testicular tumors demonstrates the close proximity of the spermatic vein to the lymph nodes draining the testicles. In the case of metastatic lymph node involvement the spermatic vein phlebography may add supplementary diagnostic information. The examination was proved successful in eight patients with malignant testicular tumors.


Some remarks to the histological classification of malignant melanoma of the skin and its prognostic values. Histological classification of human skin malignant melanoma as recommended by WHO melanoma group renders the first useful orientation in regard to the biological behavior of the tumor, but it cannot give any further clinical outlook. It would be therefore desiderable to complete the histological examinations with enzymatic and immunologic examinations performed during the treatment of the patient and thus try to gain a basis for a prognostic evaluation.


Morphological analysis of malignant melanoma cases with prolonged survival. Retrospective morphological analysis of 145 malignant melanoma cases was carried out to prove the prognostical importance of some morphological characteristics of the tumor. The cases were divided into two groups according to the survival time. The majority of the tumors with long survival time showed little capacity of invasion, while those with short survival time invaded at deeper levels of the dermis. Other features seemed to be of no prognostical relevance. Difficulties in determining the depth of invasion exactly were also discussed.


The occurence of collagen type II in bronchogenic carcinoma. It has been evidenced in a single case of bronchogenic carcinoma, that the proportion of collagen type II is increased in the diseased tissue. During the experimental work the collagenous stroma was isolated, subjected to cyanogen bromide cleavage and the relative proportion of individual types of collagen was judged according to the occurence of alpha1(I)CB3 and alpha1 (II)CB3 peptides. The nature of these peptides was proved by the chromatographic behavior during CM-cellulose chromatography, Ultrogel AcA 54 separation and by their amino acid composition.


Hemangiopericytoma.

Hemangiopericytoma. Description of e hemangiopericytomas noted in a 25-(female), 24-(female) and 44-(male) year old patient. Histological examination revealed, besides characteristic appearance of tumor cells, typical arrangement of reticuline. The authors discuss the histological criteria for diagnosis and differential diagnosis and judging benignity and/or malignity of hemangiopericytomas.


Short communication: a new technique in immunosuppression of Syrian hamsters xenografted with human tumors. Application of hyperimmune rabbit antisera against mouse lymphomas (6C3HED lymphoma, NK lymphoma) or against rat leukemic cells (RBA-34-Le leukemia) caused a considerable degree of lymphocyte depletion in hamsters.


Hyperuricaemia as an index of the response to chemotherapy in solid tumors. A transient increase in uric acid level following administration of high doses of Cyclophosphamide in the 1st course of cytostatic therapy applied for various solid tumors (mostly lung cancer) was observed in 10 patients with measurable disease simultaneously with complete or partial (above 50%) regression of the tumor. The same effect was noted in further 5 patients, who, however, had non-measurable disease. On the other hand, the clinical course of the disease and survival were similar in these 5 patients and in the former 10 patients. No corresponding increase in the uric acid level was observed in 87 patients with similar disease and treatment, but not responding to chemotherapy and with short survival. It is concluded, that hyperuricaemia may indicate responsiveness to chemotherapy in cancer patients with non-measurable disease.


[Distal ulnar nerve compression at the wrist. "Loge de Guyon" and "deep ulnar branch" syndrome (author's transl)]. The distal non-traumatic ulnar nerve compression syndrome can be dividded into two types: -i) the proximal (paralytic) type caused by compression in the "Loge de Guyon", with involvement of both the superficial sensory and the deep branch, including the motor branch to the hypothenar muscles, and, ii) the distal, more common, purely motor type (the deep ulnar branch syndrome) with paresis of the interossei and the adductor pollicis, and less commonly of the hypothenar muscles. Whereas the proximal type has various causes, particularly pressure and occupational trauma, the distal type is almost exclusively the result of extra-neural ganglion cysts. An accurate diagnosis is made possible by electromyography and nerve conduction studies. The sensory nerve action potentials, distal motor latency to the hypothenar and adductor pollicis muscles, and the corresponding muscle action potentials after nerve stimulation are pathologically altered, according to the type of lesion. Although spontaneous recovery may occur, operation is the treatment of choice, provided that simple pressure palsy is eliminated.


Subdural haematoma (effusion) and internal hydrocephalus. It is unusual to encounter a case where subdural haematoma (effusion and internal hydrocephalus coexist and are progressive. Often, when the two diseases are concomitantly present, the pathology of one complicated the other. The pathology of subdural haematoma (effusion), complicated by internal hydrocephalus, and problems involved in the diagnosis and treatment of such cases are described, with particular reference to three such cases treated by the authors, and a review of the literature. When cerebral angiography is used as a follow-up study for postoperative subdural haematoma (effusion), it is necessary to direct attention not only to the disappearance of the subdural clear space but also to the possibility of the occurrence of hydrocephalus. If the intracranial pressure is increased and convulsive seizures appear after a shunting operation for hydrocephalus, it is necessary to consider not only shunt dysfunction but also post-shunt subdural haematoma (effusion).


[Concerfing the E.E.G. changes after the Spiller-Frazer operation for the treatment of trigeminal neuralgia (author's transl)]. A follow-up of 28 patients with trigeminal neuralgia, with E.E.G. examinations was carried out at periods of 6 months to 4 years, after they had been operated on by the Spiller-Frazier method. Acturally in 14 out of the 28, discrete focal changes were observed but they were however, not so marked that one could speak of an actural focus. In comparison with the findings of other authors, the trivial nature of the changes is emphasized and it attributed to the pre-operative preparation, the position of the patients and to particular features of the operative technique.


Successful operative treatment of an aneurysm on a left persistent hypoglossal artery. The authors report on a case of a saccular aneurysm on a primitive hypoglossal artery in a patient who sustained a subarachnoid haemorrhage. The conditions of diagnosing a primitive hypoglossal artery and principles of development are briefly discussed. The first successful direct operative treatment of this rare aneurysm is reported.


[Chronic epidural intraspinal abscess following lumbar puncture (author's transl)]. Symptoms clinical course, and also statistical data are recroded for a 60-year-old man with a chronic epidural abscess in the lumbar vertebrae 3/4 following a lumbar puncture. Acute and chronic epidural intraspinal abscesses are discussed in relation to the relevant literature.


Gonadotropin secretion and hypothyroidism. Hypothyroidism is generally associated with hypogonadotropism. Occasionally, however, increased gonadotropin concentrations are encountered. The mechanisms, presumably hypothalamic, which determine the gonadotropin shift are unclear. A case report of hyperprolactinemic hypothyroidism with associated hypergonadotropism is presented. The previous literature is reviewed. It appears that hypothyroidism is generally associated with a decrease in the gonadogropin secretion. However, hypothyroidism with exxagerated hTSH secretin and hyperprolactinemia can be associated with increased gonadotropin secretion.


Mixed gonadal dysgenesis without virilization. A 19-year-old phenotypic female with primary amenorrhea and 45X,0/46X,Y chromosomal mosaicism was found to have asymmetrical gonadal dysgenesis. Her lack of virilization precludes her precise categorization in the current nomenclature of gonadal dysgenesis and she is considered a unique variant of the syndrome of mixed gonadal dysgenesis.


Diagnosis of pregnancy with a radioreceptor assay for hCG. A new serum assay for human chorionic gonadotropin, the radioreceptor assay (RRA), was compared with three commercial urinary agglutination inhibition pregnancy tests (AITs) in a group of women with suspected early pregnancies and ectopic gestations. The accepted definitions by which a laboratory test is characterized, including clinical sensitivity and specificity as well as predictive value of positive and negative tests and efficiency, were calculated for each test in three different time periods of gestation: less than 7 days, between 7 and 14 days, or more than 14 days after the expected menses had been missed. The results of the study showed that the RRA had greater clinical sensitivity and efficiency than the AITs in cases of both early gestation and ectopic pregnancy. The RRA has the disadvantages of requiring the capability to handle radioactive materials and gamma counter. This test is chiefly useful for those patients desiring early termination of pregnancy and those infertility patients anxious for early confirmation of pregnancy.


Microinvasive squamous carcinoma of the cervix: definition, histologic analysis, late results of treatment. The surgical tissues and clinical records of 54 surgically treated patients with microinvasive carcinoma of the cervix were retrospectively analyzed. Utilizing a definition that limited microinvasion to a depth of 3 mm, and excluded lymphatic and blood vascular involvement, the incidence of regional metastases in 37 patients for whom lymph nodes were available for study was 0%. Confluence of microinvasion did not imply a greater potential for metastatic spread or a worse prognosis. Lymphatic and blood vascular permeations were associated with nodal metastasis in one of four lesions which otherwise were microinvasive. Random cervical biopsy alone was inadequate for the diagnosis of microinvasion. Cone biopsy demonstrated an accuracy of 83% in diagnoses, but failed to eliminate intraepithelial or microinvasive carcinoma in 78% of the hysterectomy specimens. It is concluded that microinvasive carcinoma, as defined in this study, can be effectively treated by conservative rather than radical means.


Treatment of advanced adenocarcinoma of the endometrium with melphalan, 5-fluorouracil, and medroxyprogesterone acetate: a preliminary study. Combination chemotherapy can produce a rapid and frequent therapeutic effect against advanced endometrial adenocarcinoma regardless of the tumor distribution. A new treatment program is described. Melphalan, 5-fluorouracil, and medroxyprogesterone acetate achieved 6 of 7 objective responses in patients. This result with combination chemotherapy is substantially better than results with single agents or hormones alone and justifies further evaluation of combinations of cytotoxic chemotherapy as part of the initial treatment of choice for patients with advanced endometrial adenocarcinoma.


Paraaortic lymphadenectomy in gynecologic malignancies confined to the pelvis. Eighty-six patients with pelvic malignancies had paraaortic node dissection; 30% had positive paraaortic lymph nodes. At the time of laparotomy, 77 patients had malignancies apparently confined to the pelvis after extensive work-up and histologic examination of tissue biopsies outside the pelvis; 20 (26%) had metastatic cancer in the paraaortic lymph nodes. Thirteen of 49 patients with cancer of the cervix, 5 of 18 with uterine cancer, and 2 of 10 with ovarian cancer had positive paraaortic lymph nodes. The value of paraaortic dissection in patients with pelvic malignancies apparently confined to the pelvis is discussed.


Adenomyosis: a neglected diagnosis.

Adenomyosis: a neglected diagnosis. Adenomyosis was present in 161 of 1619 consecutive hysterectomy specimens. Adenomyosis coexisted with other pelvic pathology in 97 women and was the only histologic finding in 64 women. Most patients were 35 to 50 years of age, parous, white, had not taken steroid hormones, had not had uterine surgery, and complained of abnormal uterine bleeding and/or pelvic pain. Adenomyosis was most associated with leiomyomata, endometrial hyperplasia and carcinoma, and endometriosis. The clinical signs of uterine enlargement and tenderness were rarely observed. The diagnosis was suspected  preoperatively in 10% of women. At surgery, adenomyosis was not recognized in 65% of patients. Adenomyosis is a disease of unknown etiology whose uncharacteristic clinical profile and frequent association with more obvious pelvic pathology make it a neglected diagnosis.


Safety and efficacy of combining obstetric and noninfectious gynecologic hospital patients. Unoccupied obstetric beds and unused delivery rooms represent inefficient use of hospital facilities and loss of revenue, both of which adversely affect the quality of care rendered patients. Hartford Hospital has permitted the admission of obstetric and noninfectious gynecologic patients to the same patient care areas of the hospital as well as use of delivery rooms by both groups of patients. Elaborate surveillance of these patients by the epidemiology section for a 1-year period (July 1974-July 1975) demonstrated no increase in the incidence of hospital-acquired infections associated with this combined approach as compared with the more traditional separation system of maternity and nonmaternity patients.


Fetal steroid levels at delivery.

Fetal steroid levels at delivery. The purpose of this study was to investigate cortisol levels in the circulation of neonates following spontaneous onset of labor. There was no significant difference of values between primigravidas and multigravidas, male and female babies, or normal and preeclamptic pregnancies. There was no significant change in mean cord plasma cortisol values with advancing gestational age, after the 33rd week. It is conceivable that spontaneous labor in humans may be preceded by a release of cortisol into the fetal circulation, and when a critical "parturient" level is reached labor becomes established.


Thromboplastic activity in amniotic fluid during pregnancy. Thromboplastic activity of amniotic fluid (TAAF) was determined in 97 normal and pathologic pregnancies using a modification of Quick's one-stage method for prothrombin time. It was shown that amniotic fluid (AF) has thromboplastic activity. This activity was found to increase with the progression of pregnancy, showing a very high correlation coefficient (r = -0.86). In cases of pathologic pregnancies such as those associated with diabetes, toxemia, IUGR, and Rh incompatibility, the values of TAAF do not differ from normal pregnancies. However, in 7 of 10 cases of postmature pregnancies the TAAF was below 45 seconds while no preterm or term pregnancy showed TAAF of less than 45 seconds.


Effects of pregnancy on the maternal lymphoid system in mice. The effects of pregnancy on the lymphocyte populations in the mouse have been studied. Though cell numbers decreased in the thymus and increased in the lymph nodes draining the parauterine area, no significant changes were seen in the proportions of thymus derived (theta allo-antigen positive) and bone marrow derived (Fc receptor positive) lymphocytes. The humoral response to sheep erythrocytes was suppressed during both syngeneic and allogeneic pregnancies following a decline coincidental with that of thymic mitotic activity. Though the observed immunosuppression could be explained by a selective lymphocyte depletion, it appears more likely to be a nonspecific effect of the steroid milieu of pregnancy.


Fetal sex determination by ultrasound.

Fetal sex determination by ultrasound. Real time ultrasonographic examination of the fetal perineal area after 30 weeks of gestation can reveal the external genitalia of the male fetus. The absence of this finding indicates a female fetus. This assessment is possible in up to two-thirds of cases, being limited only by the fetal presentation, position, and the estimated volume of amniotic fluid. Using this technique, fetal sexing was accomplished in 366 cases with an overall accuracy rate of 95.6% (correct in 99.5% of those diagnosed as males and in 91.5% of those diagnosed as females).


The viscoelastic nature of chorioamniotic membranes. This study establishes the viscoelastic nature of the human chorioamniotic membrane. Membrane tissue taken from term pregnancies was placed in a state of biaxial stress consistent with the condition in which membranes rupture in normal healthy patients. The phenomena of creep, stress relaxation, elastic recovery, and time-dependent load deformation relations were demonstrated. The experiments needed to produce these phenomena are described. The results are graphically reported. The experiments were performed using samples of fetal membranes and compared to gum rubber which is a known elastic material. From the results, one can conclude that fetal membranes are viscoelastic. The flow freely under applied stress, and they have elastic and viscous properties which are time dependent.


An experimental study of trophoblast growth in the lung. Trophoblast can be grown from blastocysts or ectoplacental cones of the mouse in a variety of extrauterine sites. An attempt was made to grow trophoblast in the lung under various conditions. In 94 mice, blastocysts, or cones, were introduced into the lung through the vascular system. Trophoblast growth never occurred. However, when blastocysts, or cones, were introduced directly into the lung, trophoblast grew in 30-50% of mice, depending on technique. Failure to grow from the intravascular position does not appear to be due to liberation of common products of ischemia because blastocysts produced normal trophoblast in the liver when implanted via the portal system, even in the presence of extensive necrosis. The inhibiting factor, which is apparently produced in the lung, is being investigated.


The influence of acupuncture stimulation during pregnancy: the induction and inhibition of labor. Uterine response to electroacupuncture stimulation of specific sites of the extremities is demonstrated in 60 pregnant women--48 cases for labor induction and 12 cases for inhibition of premature labor. In the 34 term, post-term, and 7 intrauterine fetal death cases, induction of labor was attempted; in 32 cases delivery was achieved, resulting in a success rate of 78%. In 7 cases of midterm abortion attempts, all failed to respond. Of the 12 cases of premature labor, with the exception of 1 case, all carried the pregnancy to term, resulting in a success rate of 91.6%. Based on these clinical observations, electroacupuncture may become a useful tool in controlling labor. The possible mechanism of action is discussed. Further investigation and standardization of this technique is proposed.


A new prenatal cardiac diagnostic device for congenital heart disease. A unique case of congenital heart disease and complete heart block diagnosed by fetal electrocardiogram (ECG) and phonocardiogram recorded initially at 32 weeks gestation is presented. The slow, regular fetal heart rate of approximately 50 beats/min with bizarre QRS and a diamond-shaped murmur beginning with the fetal QRS complex made a diagnosis of complete heart block (CHB) and associated congenital heart disease highly probable. Direct fetal electrocardiograms (FECG) recorded during labor and vaginal delivery at term confirmed the diagnosis of completel atrioventricular block. Cardiac catheterization at 1 day of age showed multiple congenital heart anomalies. The infant developed signs of congestive heart failure and transvenous pacemaker was successfully placed; however, he died at 9 days of age of sepsis and renal failure.


The etiology of preeclampsia: a hypothesis. Recent investigations into the pathophysiology and immunobiology of preeclampsia have strongly implicated immunologic dysfunction as a central feature of this disease. A hypothesis is herein presented which unifies current research with clinical manifestations, in an attempt to clarify the etiology of this obstetric enigma.


Fetal monitoring: psychologic consequences and management recommendations. The psychologic consequences of fetal monitoring were investigated by means of structured interviews with 35 postpartum women. Both beneficial and detrimental effects associated with the use of fetal monitors were identified. Personality characteristics and past experiences with pregnancy and labor were found to be factors shaping the manner in which the monitor was experienced. Areas of prepartum and intrapartum care indentified in which the potential for maximizing the beneficial aspects of monitoring and reducing the detrimental ones exist. Specific management recommendations are given.


Four-vessel umbilical cord associated with multiple congenital anomalies. A case is described in which it was found at autopsy that the umbilical cord of a macerated stillborn infant had four patent vessels (two arteries and two veins) throughout its length. This was due to a rare persistence of the caudal portion of the right umbilical vein. The infant had multiple congenital anomalies including complete thoracic ectopia cordis, a symmetrical bifid liver, severe bilateral cleft lip and palate with absent soft palate and uvula , and cecum mobile. The autopsy findings are detailed and the relevant literature and embryology briefly discussed.


[Influence of mutant genes on crystallin synthesis in the forming mouse lens. II. Fidget and ocular retardation genes]. The beginning of synthesis and the localization of alpha- and gamma-crystallins in the developing lenses of the 10-13 and 15 days old mouse embryos of the genotypes fi/fi +/+, +/+ or/or, fi/fi or/or and +/+ +/+ were studied by means of indirect immunofluorescence. The synthesis of crystallins in the mutant embryos with the exception of the embryo +/+ or/or was shown to begin somewhat later than in the normal ones but to proceed in all defective lenses, irrespective of the degree of defect. Hence, the activation of the genes controlling the synthesis of alpha-crystallins begins at the early stages of lens development and the synthesis of these proteins proceeds even during the abnormal with the slowing down of the formation of primary lens fibers. In the cases of strong defects of morphogenesis in the fi/fi +/+ and, especially, fi/fi or/or, embryos gamma-crystallins were not detected. The synthesis of gamma-crystallins appears to begin at the final stages of lens fiber differentiation.


[Morphofunctional features of the development of the hypothalamo-hypophyseal neurosecretory system and adenohypophysis in the round goby Gobius melanostomas Pallas during early ontogenesis]. The formation of the hypothalamo-hypophysial neurosecretory system (HHNS) and adenohypophysis in the round goby takes place during the embryogenesis. The HHNS functional differentiation begins earlier than the anatomical one. The Homori-positive neurosecretory material was found in the neurohypophysis of one day old larvae. The first, within 7-10 days after the hatching, to be differentiated are the acidophilic cells of mesoadenohypophysis, then, on the 10-15th day, the acidophilic cells of proadenohypophysis and on the 20-25th day the basophilic cells of mesoadenohypophysis which perform the thyrotropic function and the cells of metadenohypophysis. The early development of the morpho-functional interrelations between HHNS and adenohypophysis is noted which ensures the realization of specific adaptations at the early stages of ontogenesis. The role of homoriphilic neurosecretory substance in the differentiation of glandular cells and the regulation of adenohypohysial functions is discussed.


[Effect of actinomycin D on development of the ocular imaginal disks of drosophila]. The actinomycin D treated discs were transplanted into imago or larvae ready for pupation to determine the period of synthesis of mRNA's engaged in eye development during the development of eye imaginal discs. When transplanting 24, 48 and 72 hrs eye imaginal discs into larvae ready for pupation, no inhibition of either eye pigment synthesis, or cuticular structure development by actinomycin D was found. When transplanting actinomycin D treated 72 hrs and prepupal eye imaginal discs into imago, the inhibition of eye pigment synthesis was found only in 72 hrs discs.


[Expression of genes controlling esterases during the embryonic development of hybrid fish]. The electrophoretic mobility of several enzymes was studied in the embryos and early larvae of the hybrids between the loach (Misgurnus fossilis) and the aquarial cyprinids and cobitids (Acanthophthalmus). The cytosol aspartate aminotransferase is represented by one protein with the same mobility at all developmental stages both in the loach and in the hybrids. Malate dehydrogenase manifests four bands of isozymes which suffer no changes during the development. The electrophoretic profile of lactate dehydrogenase remains constant (10 isozymes) until hatching, but only 5 isozymes are found in the 5 days old larvae. Similar changes occur in the Misgurnus X Acanthophthalmus hybrids. The nonspecific esterases are represented by several proteins with different activities; their number increases after hatching. In the oocytes and adult specimens of Acanthophthalmus a characteristic and very active esterase was found which is absent in the loach. In the Misgurnus X Acanthophthalmus hybrids this esterase appears prior to the hatching and its activity later increases. Thus, the expression of the gene of one esterase begins in the end of embryogenesis.


[Fibroblast differentiation during collagen formation]. The successive differentiation in the series lymphocyte--(lymphocyte-type cell--precursor)--weakly differentiated cell (polyblast)--profibroblast--fibroblast was shown by means of scanning and transmission electron microscopy. In the focus of aseptic inflammation and in the zones of pneumosclerosis (silicosis), the ultrastructural and cytochemical cell rearrangement took place which was accompanied by the development of protein synthesizing organelles and the formation of folded surface. The collagen fibers run from the surface of the differentiated fibroblasts in the ground substance and preserve the direction of their growth with respect to the spatial position of cells.


[Sources of several errors in DNA cytofluorimetry]. It was shown that serious errors in DNA cytofluorimetry may be due to incorrect illumination of photocathode of the photomultiplier in the cytofluorimeters and non-observance of the requirements to the nuclear structures of the cells under measurement with respect to their chemical integrity and thickness. The methods of the optimal illumination of photocathode in the cytofluorimeters and the criteria of selection of the nuclear structures on slides are considered with the aim of obtaining the objective results of DNA cytofluorimetry.


[Instability and stability in biological morphogenesis]. The concept of morphogenesis is determined and the mathematical image of the developing system is considered. A certain amount of stable and unstable states and slow changes of the potential relief (parameters) are inherent in the latter. The developing systems are intermediate between the deterministic and statistic ones. They are distinctly multiple-levelled. The microprocesses of morphogenesis and the laws of macromorphogenesis are described, the instabilities and stable periods of morphogenesis are considered. All of them in the multiple-leveled system tend to the formation of through hierarchies, or cascades, where the upper levels parametrize the lower ones. This tendency increases as the evolutionary progress proceeds. The genetic regulation is considered also as a parametric regulation in the domains of instabilities. The approach contemplated may be considered both as the generalization of the available data and as the programme of investigation, more adequate to the biological reality than the causal-analytical methodology.


[Glycolysis in the eye tissues of the rabbit in ontogeny. II. The dynamics of the changes in the level of glycolysis and lactic acid intermediates]. The level of intermediates of glycolysis (hexose monophosphates, fructose-1,6-diphosphate, pyruvate) and the rate of lactic acid synthesis (under the aerobic conditions without substrates and in the presence of glucose, glucose-6-phosphate and fructose-1,6-diphosphate) were measured in the eye tissues (retina, iris, ciliary bodies, uvea) of rabbits of different age. The rate of lactic acid synthesis under the aerobic conditions in the retina and uveal tract increases of the latter the rate of lactic acid synthesis was the highest. The greatest increase in the lactic acid content was observed during the first 15 days of postnatal development.


[Multiple forms of alkaline and acid phosphatases in rat tissues in the postnatal period]. The content of multiple forms of alkaline and acid phosphatases in different tissues during the rat postnatal ontogenesis was studied by means of electrophoresis in agar gel. The distribution of enzymes in subcellular structures and their sensitivity to some inhibitors are estimated.


[Effect of colchicine and 3H-thymidine on the proliferation and mitotic cycle of chick embryo cells in the gastrulation period]. The effect of colchicine and 3H-thymidine on the proliferation and mitotic cycle of cells of different rudiments of the chick embryo has been studied during gastrulation. Colchicine (1-10-6 g/ml) was shown not to influence both the portion of cells synthesizing DNA and entering mitosis and the intensity of DNA synthesis. No changes in the intensity of cell entrance in mitosis and the frequency of mitotic figures were found following the injection of 3H-thymidine (4.1 Cu/mM) at a dose of 2.5 muCu per egg. Taking into account the great possibilities of the complex utilization of stathmokinetic and autoradiographic methods for studying the kinetics of developing cell populations, a conclusion is drawn that the chick embryo at the early developmental stages is a convenient model for such an analysis.


[Malate dehydrogenase isoenzyme induction in an Acetabularia chloroplast fraction with nuclear transplants]. Changes in isozymes of malate dehydrogenase (MDH) in the chloroplast fraction under the transplantation of the A. crenulata nuclei in the A. mediterranea anuclear fragments were studied by means of electrophoresis in polyacrilamide gel. Within 30 days after the transplantation the nucleus induces in the chloroplast fraction MDH isozymes similar by the electrophoretic mobility with those of A. crenulata. The induction of such isozymes was observed both in the plants with the morphological characters of A. crenulata and the fragments which have not formed the reproductive caps, as well as under the transplantation of a small amount of cytoplasm from A. crenulata with chloroplasts in the anuclear fragments of A. mediterranea.


Restoration of binocular vision.

Restoration of binocular vision. Numerous studies have shown that pseudophakic surgery is a better (because it is a more natural) method of restoring binocularity than contact lenses or aphakic spectacles provided that the potential for binocular vision was present before the onset of the cataract(s). However, this restoration is achieved more easily in some groups of patients than others. Unilateral: Excellent prognosis for binocularity is retained for many years--even 50-60 years--in adult unilateral traumatic cataract/aphakia. At the other extreme are patients born with one normal eye and the other containing a well-marked cataract. In unilateral traumatic cataract/aphakia in children the potential for restoration of binocularity is related to age--the older the child, the better the chances. To achieve binocularity central vision must not fall below 20/70 in each eye. Bilateral: There is not much to choose between pseudophakia and contact lenses; both are effective in restoring binocularity, and both are superior in this respect to cataract spectacles of keratophakia.


Iris plane pseudophakoi (Copeland lens): prevention of synechiae formation. The iris plan Copeland lens was inserted in 56 cases. A high incidence of synechiae and retrolental membrane formation was noted. This could be prevented or reduced in severity by the controlled use of pupil dilatation in the postoperative period.


Pars plana vitrectomy for complications of intraocular lens implantation. Several clinical situations have been presented in which pars plana vitrectomy has proven beneficial in the treatment of vitreous complications of lens implantation. Removal of the central opacity and enlargement of the pupil are essential to improve vision, relieve pupillary block and achieve an adequate view of the retina. Pars plana vitrectomy offers a method for the controlled removal of membrane, vitreous and iris tissues without unnecessary distortion of anterior segment anatomy.


Ultrasonic fragmentation for retroimplant membranes and pupillary block. Retroimplant membranes may produce a reduction in vision and/or pupillary block glaucoma. Ultrasonic fragmentation through the pars plana is a quick and easy method for relieving the condition. The technique is described in six cases in which it has been used.


Cystoid macular edema following intraocular lens implantation. This presentation recounts the original description of CME and the more recent developments associated with intravenous fluorescein angiography in its study and diagnosis. The work of previous authors to show the incidence of CME and its possible prognosis are reviewed. Our findings in a retrospective study agree with the other authors and show that there is no particular increase in CME following intraocular  lens implantation regardless of the type of surgical procedure used. It is established that vitreous loss does increase the incidence of CME. A prospective study with routine intravenous fluorescein at six weeks is presented and shows an incidence that is below that found by other authors when it was performed following routine intracapsular cataract extraction.


Indications for intraocular lens removal. 1. The indications for removing an intraocular lens (IOL) are: A. Chronic uveitis B. Endothelial corneal dystrophy C. Uncontrollalbe glaucoma D. Metal loop cutting pupillary sphincter E. Gross decentration of IOL (fibrous bands) F. Extraocular dislocation of IOL G. Recurrent severe hyphema H. Development of rubeosis iridis I. Removal of iris (1) Iris tumor (2) Epithelial downgrowth J. Endophthalmitis K. Unilateral IOL in pending bilateral aphakia 2. The following may be indications for removing and/or replacing and/or replacing an IOL: A. Wrong dioptric power B. Foreign body attached to IOL C. IOL covered with pigment D. Repair retinal detachment after extracapsular cataract extraction E. Choyce lens too short F. Dannheim IOL with absorbed supramid loop tips G. Dislocated Ridley IOL H. Sclero-conjunctival erosion of Strampelli's "external-fixation" IOL loop. The preceding analysis of problem areas is meant to specifically define when and why to remove or replace an IOL, or institute alternative forms of treatment. One is advised to obtain consultation or a second opinion before embarking on lens-removal surgery.


Intraocular lens in laboratory animals.

Intraocular lens in laboratory animals. This report summarized the findings in 40 rabbit eyes undergoing extracapsular cataract extraction, 20 of which underwent intraocular lens implantation. The parameters of postoperative evaluation are shown to be limited by the susceptability of the rabbit cornea to corneal edema in the early postoperative phases. The only apparent parameter of statistical importance in this series, however, was the day at which the intraocular lens implanted eye returned to normal compared to the day that the non-implanted eye returned to normal. The fact that there is a 13-day difference in these eyes and the fact that this difference is statistically significant may be important. Pathologic examination of lens implanted eyes has shown that the surgical objectives of intracapsular loop fixation are quite feasible. Microscopic study also showed that there is minimal tissue response to the materials placed in the anterior chamber in this type of surgery.


Intraocular lens surgery on a resident's service. Twenty-three patients had intraocular lens surgery performed by eight separate ophthalmology residents over an eighteen month period of time. Adequate technical results were achieved in 19 of the 23 cases. Three patients had visual complications directly related to the intraocular lens surgery: two with bullous keratopathy and one with cystoid macular edema. By restricting surgical indications to older patients with good vision in the fellow eye and using general anesthesia in conjunction with the operating microscope, osmotic agents, intracapsular surgery, and close operative supervision, it is hoped that results will justify continued use of intraocular lenses on our resident's service.


The need for intraocular lens implantation in children. The intraocular lens offers an additional experimental parameter to be considered for the visual rehabilitation of children with traumatic or unilateral infantile cataracts. The disadvantages of aphakic spectacles or contact lens and amblyopia have committed many of these eyes to the status of visual cripples. In this series of 41 patients, with a maximum of 24 months follow-up, it has been concluded that the IOL may be successfully implanted.


Orthoptic consequences of Binkhorst lens implantation for unilateral cataract. Stereoacuity levels regained after uniocular lens implantation for unilateral cataract are related to the final visual acuity of the operated eye. They compare unfavorably with levels reported in normal populations and are unrelated to the period of monocularity and the residual optical defects of the operated eyes. Using random dot stereograms as a criterion, over a third of thirty-five patients remained stereoblind after treatment.


Extracapsular surgery and lens implantation. Extracapsular surgery is an ideal type of cataract surgery in combination with lens implantation insofar as stability and fixation of the lens is greatly enhanced. However, a number of complications can be expected. The main probelms of extracapsular surgery is posterior capsule opacification. This is due to regeneration of germinal lens fibers. To prevent this a complete removal of cortical lens matter is advisable, even in lens implantation. This however requires special lenses, which have additional iris fixation.


Lens implantation surgery in the second eye. In a series of 730 patients who underwent lens implant surgery, 44 (6%) had bilateral implants. Eighty-eight percent of these patients had at least one year's interval between operations and 50% more than two years. Surgery on the first eye resulted in vision of 20/40 or better in 86% of patients. Eighty-three percent of patients were 20/40 or better in the second eye following surgery. The principal cause of vision less than 20/40 was senile macular degeneration. Follow-up observation ranged from 4-96 months. Conservative criteria are advised for bilateral implant surgery, with an appropriate interval between operations considering the increased complexity of the implant procedure.


The Choyce Mark VIII anterior chamber implant: primary and secondary implantation compared. The author only started primary Mark VIII implantation in 1970, and has only a modest total of 50 cases at this time. Therefore it is premature to draw too many conclusions when comparing this small series with secondary implantation going back over 20 years and covering approximately 1200 years. However the following tentative conclusions are drawn: 1. When confronted with pre-existing aphakia (particularly unilateral) the visual and psychological results of secondary Mark VIII implantation are excellent over a wide spectrum of indications and ocular states. It is a very adaptable and versatile implant--a true "Implant for all Seasons" as Clayman has said. 2. Primary Mark VIII implantation shows considerable promise, particularly when allied to a well-thought-out and carefully-executed microsurgical technique as devised by Tennant. The author is performing more and more primary implantations and regards second eyes as a very favorable indication.


Results of primary and secondary implants using Choyce Mark VIII lenses. The author's experiences with the Choyce Mark VIII implant have been statistically reviewed. The results reveal no significant increase in complications over standard cataract extraction without implantation. Secondary implantation is compared with primary implantation. The results seem to support the author's position that secondary implantation with the Choyce lens carries a 3-5% incidence of complications which must be weighed against the patient's need for further rehabilitation. The importance of fixation in implantation has been reviewed from an historical standpoint to support the conclusion that the Choyce lens owes much of its superior results to its ideal fixation and lack of pseudophakodonesis.


Intraocular lens implantation -- analysis of 500 consecutive cases. The author analyzed 500 consecutive cases of intraocular lens (IOL) implantation performed in the past five years: the patients were unselected; 0.2% required enucleation (one case of epithelial downgrowth); 2% needed IOL removal; 3.6% suffered retinal detachment; males were three times as prone to retinal detachment and "vitreitis" as females; 7.5% experiences IOL subluxation; 10% required subsequent surgery for a variety of complications; 15% demonstrated clinical cystoid macular edema (CME); the lowest incidence of CME occurred with Copeland lenses (3.9%); the highest incidence of CME was seen with IOL's with metal loops (33%); 21% had CME following secondary implantation; 61% had no complications during surgery or the entire follow-up period. 79% had industrially-useful vision (20/40 or better); 95% had intracapsular extraction; there were no cases of endophthalmitis.


Corneal edema: iris-clip lens implantation and simple intracapsular extraction compared. Corneal edema following intracapsular lens extraction and iris-clip lens implantation was compared by assessing corneal thickness and epithelial edema. In a retrospective study the corneal thickness of twenty patients who had intracapsular lens extraction in one eye only was compared with twenty-six patients with iris-clip lens implants in one eye. There was no significant increase in corneal thickness in the operated eye in either group. In a prospective randomized controlled study, a smaller number of patients, had serial measurements of corneal thickness pre- and postoperatively. There was an increase in thickness in the immediate postoperative period for both groups. However, there was no significant difference between eyes which had simple extraction and those which had implants. The implanted eyes however had greater mean increase endothelial trauma in the initial period, compared to eyes with cataract extraction alone.


Secondary intraocular lens implantation. Mere aphakia is not an indication for secondary intraocular lens implantation. However, many patients with positive indications may be benefited most strikingly by this procedure. These indications are illustrated and results of the author's first 65 secondary implantations are analyzed.


Iridocapsular lenses versus iris-clip lenses: comparison of the results and complications of 100 of each. The results and complications of implantation of 100 iridocapsular and 100 iris-clip lenses are evaluated. The follow-up period for the first group varied from one to 25 months (mean 12 months) and from one to 43 months (mean 27 months) for the second group. I performed all of the operations and most of the follow-up examinations. Of the patients with iridocapsular lenses, 86 percent and of those with iris-clip lenses, 87 percent obtained a visual acuity of 0.5 (6/12) or better. Binocular vision, positive depth perception, and a small degree of aniseikonia (3% or less) are evident optical benefits. The complicatioons most frequently necessitating a second operation were retained lens material (17%) and repositioning the pseudophakos (6%) in the iridocapsular group. The four-loop lenses caused fewer problems; in one case, posterior luxation necessitated its removal.


Corneal thickness measurements following intraocular lens implantation. Corneal thickness measurements were carried out on patients who had undergone combined phacoemulsification cataract extraction with simultaneous intraocular lens implantation in one eye at least six months prior to the date of measurement. The unoperated eye served as control. Another group of patients who had undergone simultaneous phacoemulsification cataract extraction combined with intraocular lens implantation were followed over a two-month period of time, serial corneal thickness measurements being performed. The results indicate that, in surgery performed by experienced surgeons on carefully selected patients, phacoemulsification cataract extraction using the Kelman technique combined with intraocular lens implantation had no significant effect on corneal endothelial function as reflected in corneal thickness changes.


Shape, number and localization of retinal tears in myopic over 8D, aphakic and traumatic cases of retinal detachment. An experience report. For this experience report we have selected out of a total of 950 eyes with retinal detachment, 373 eyes and have sorted them out into three study groups: myopia over 8 d (197 eyes including 14 bilateral detachments), surgical aphakia (102 eyes) and traumatic detachment (74 eyes). With the help of tables and figures we tried to point out the form, number and localization of retinal tears in the eyes with retinal detachment in the above-mentioned groups. For fundus examinations we used routinely the binocular indirect ophthalmoscope without and with scleral depressor and the Goldmann three-mirror contact glass, also without and with scleral depressor. The striking features of the main types of retinal breaks in the three groups are commented, statistically analysed and compared.


[Is angiodiathermocoagulation an outmoded operation?]. Following a short summary of the anatomical and physiological aspects of the surgical procedure, the authors present a series of 320 eyes operated upon by the method of angiodiathermocoagulation. Open-angle glaucoma, followed by aphakic glaucoma, respond the best to this procedure, the expected number of good results being approximately 25% where the criteria are severe. The low percentage of severe complications represents one of the greatest advantages of angiodiathermocoagulation, which may be recommended in desperate cases.


[LP-X in the first month of life (author's transl)]. An abnormal lipoprotein can be detected in the sera of patients suffering from intra- and extrahepatic cholestasis. The specificity of LP-X detection for the diagnosis of cholestasis in adult persons was proved by extensive investigations. The aim of this study was to examine the specificity of LP-X with regard to cholestasis in the postnatal phase of premature and newborn infants. 1056 sera of 270 newborns were tested and in 75% of these cases LP-X was found to be positive. Three hypothetical explanations are given concerning the appearance of LP-X in the sera of premature and newborn infants. The semi-quantitative determination of LP-X also represents a possibility for differential diagnosis of obstructive jaundice in the neonatal period.


[Meningeal inflammatory diseases causing transverse lesions in childhood (arachnoiditis spinalis chronica and pachymeningitis spinalis hypertrophicans). Diagnosis and treatment (author's transl)]. The Arachnoiditis spinalis and the Pachymeningitis spinals are seldom the cause of neurologic deficit. During infancy both illnesses are extremely rare. One illness with a Arachnoiditis spinalis chronica adhaesiva cystica and, for the first time one with a Pachymeningitis spinalis hypertrophicans could be observed. The signs show parallels to spinal tumors, but when inflammation is the origin, the early starting symptoms of tumors appear relatively late. Symptoms of the radix remain dominant. Myelography shows a typical drop shaped block in the case of Arachnoiditis. Diagnosis can be asured only histologically. Surgery may prevent remaining defects of the spine by decompression and may obtain a permanent success by the removal of local processes. When expanded changes occur, an additional chemotherapy with Prednisolon, perhaps in combination with Endoxan may cure the patient, as shown in our two cases.


[Simple examination of spastic movement disorders of the lower limbs in the infant age]. In 334 children active dorsiflexion of the feet was tested in order to screen for spasticity of the lower limbs. The conditions were: 1. The child lying supine. 2. The head turned actively and if this is not possible passively to the side of the examined foot. 3. Passive extension of the child's hip and knee of the examined side by the examinator. 4. Stimulation of the skin at the lateral and lower part of the shin, or the dorsum pedis or the anterior part of the toes and the planta pedis to provoke active dorsiflexion of the foot. Stimulation is done by the fingers of the examinator or by a slight touch with an ordinary handbrush. Dorsiflexion of the foot is graded "normal" if it surpasses 90--100 degrees, "suspicious" if it only reaches 90 degrees and "pathologic" if 90 degrees cannot be reached or if this can be done only on the medial side or if there is constant clawing of the toes even with sufficient dorsiflexion. We have examined 334 children; 260 of these were younger than one year. The results of this kind of stimulated dorsiflexion of the foot were compared with the results of the usual extensive neurological examination with regard to spasticity of the lower limbs (see literature) and with both of VOJTA's most sensible postural reactions. The following conclusions are drawn: 1. Spasticity of the lower limbs can be excluded with a high degree of probability when dorsiflexion of the feet is graded "normal". 2. If the dorsiflexion is graded "suspicious" or "pathologic" a more thorough neurological examination is warranted and if necessary short-term controls. 3. The results of this examination are in good agreement with the one of VOJTA's most sensitive postural reactions to indicate spasticity of the lower limbs.


[Excretion of D-glucaric-acid in newborns with non-hemolytic hyperbilirubinemia after phenobarbital treatment (author's transl)]. The excretion of D-glucaric-acid during 24 hours in the urine, which is a measure for the activity of microsomal liver enzymes, was determined in 33 newborns. From 22 newborns with non-hemolytic unconjugated hyperbilirubinemia 11 were treated with 7.5 mg phenobarbital per kilogram bodyweight 5 days and afterwards the excretion of D-glucaric-acid was measured. In contrast to the untreated newborns there was a significant decrease of the bilirubin concentration in the serum and a concomitant increase of the D-glucaric acid excretion from 0,052 mumol/day/kg to 0,388 mumol/day/kg (mean values). A negative correlation (r = -0,51) could be calculated between the bilirubin concentration in the serum and the excretion of D-glucaric-acid after treatment with phenobarbital.


[Usefulness of the serum-xylose-test in comparison with small-intestine morphology in the malabsorption syndrome]. In 148 children, 4 months to 14 1/2 years old, 192 serum-xylose-tests (XT) and small bowel biopsies have been performed because of suspected intestinal malabsorption. The results of the XT and of the biopsies were compared to investigate the diagnostic value of the XT with respect to the morphology of the small bowel mucosa. Further we wanted to determine at which time after the oral intake of xylose the best correlation of XT and morphology can be expected. In children with normal mucosa the XT differed significantly from those with subtotal mucosal atrophy but not with partial villous atrophy. However, partial villous atrophy could be differentiated from subtotal villous atrophy with the same test. In children with subtotal villous atrophy a statistically significant age-dependency could be observed, comparing children being less or more than 2 years old and also a dependency from periods with gluten-free diet. Partial villous atrophy with or without coeliac disease cannot be differentiated by means of the XT. Best correlation of the XT and the morphology of the small bowel mucosa can be found 60 minutes after the oral xylose load; no additional information is obtained by more blood-xylose-determinations (e.g. 30, 90, 120, 180 minutes). Because of the rather high standard deviation of the individual blood xylose values no exact prediction can be made from the XT to the mucosal morphology. Therefore the XT is only of value for screening purposes and its results should not influence the indication for a small bowel biopsy, derived from clinical considerations.


[Frequency of iron deficiency and iron deficiency anaemia in infancy and childhood (author's transl)]. 266 children with iron deficiency were treated over a period of 2 years. The incidence rate and age distribution did not deviate much compared with former results. A different incidence of iron deficiency was found when 120 healthy children from 2 socially and economically different groups were examined. In both groups together the incidence rate of iron deficiency was 19%. But while in the socially higher standing group only 5% were afflicted, the other group showed 33%. This difference questions the value of generally iron medication and favours the opinion that iron deficiency indicates that children have not been looked after properly.


[Current use of the sweat test (author's transl)]. A positive sweat test is still the principal diagnostic feature of cystic fibrosis. Repeated tests are mandatory in positive, borderline and any suspect cases. Pilocarpine iontophoresis and quantitative evaluation of sodium and/or chloride are the only acceptable test methods. Every effort must be made to avoid contamination of the sweat sample. Diagnostic values are more than 50 mequ/l for sodium and more than 60 mequ/l for chloride.


Actin-like contractile protein in carbon tetrachloride-induced cirrhosis in the rat. Cryostat sections of livers from rats treated with carbon tetrachloride (CCl4) for 12 weeks were examined by indirect immunofluorescence for reactivity with human serum containing smooth muscle antibody (SMA). Increased binding of SMA serum to hepatocytes was observed as early as the first week of CCl4 treatment and remained enhanced during the 12 weeks of study. No difference in staining intensity was observed between pre-cirrhotic liver parenchymal cells and hepatocytes in regenerative nodules of frankly cirrhotic livers. In addition, granulation tissue fibroblasts in cirrhotic livers showed strong reactivity with SMA serum. The specificity of the staining reaction for actin was established by its prevention on neutralization absorptions of the serum with homogenates of smooth muscle or extracts containing actin derived from smooth muscle. Circulating SMA was not demonstrated in the serum of rats at any phase of the study. The observations show that there is an increased expression of actin-like protein in regenerating hepatocytes and granulation tissue fibroblasts in cirrhotic livers.


Fibrin-bound tumour cells on a sclerosed mitral valve. The association of fibrin and tumour cells on a sclerosed mitral valve in a 62-year-old woman is described. This was the first indication of malignant disease but bilateral ovarian cancer was proved two months later. ino further tumour deposits have been found in fifteen months. The tumour deposit on the valve was most likely a metastasis but primary heart valve sarcoma has not been positively excluded. If the lesion was a secondary deposit this has possible implications for the role of fibrin in metastasis in humans.


Assessment of workload in the microbiology laboratory. Workload measurement is necessary for laboratory management and planning. Adaptation of the College of American Pathologists' scheme to the requirements of a large clinical microbiology laboratory is described. Our method of applying basic work values is simpler and the calculation of workload is easily adapted to take account of alterations in laboratory method. The resulting system of workload measurement can be instituted without undue effort.


Basement membranes of small cardiac vessels in patients with diabetes and myxoedema: preliminary observations. Ultrastructural observations on the basement membranes of small vessels from hearts of patients with diabetes, myxoedema and neither disease collected post mortem, reveal that the membranes of those with diabetes are nearly three times as thick as those in normal hearts (P less than 0.001), while in patients with myxoedema they are twice normal thickness (P less than 0.001). A significant difference was demonstrated between the thickness of the basement membrane in patients with diabetes and those with myxoedema (P less than 0.001).


The mast cell: II. Distribution and maturaiton in the peritoneal cavity of the young rat. In rats aged 1/2 to 60 days, the development of the mesentery and omentum involves a substantial modification of the inital lymphatic supply of these membranes and the postnatal development of 'milk spots' of the omentum. In both membranes, mast cells are scarce at birth but progressively increase in number and maturation with increasing age of the rat. In the paravascular zones of the mesentery, mast cells are particularly associated with lymphatic vessels, rather than with blood vessels. Mast cells are also scarce at birth in the free peritoneal fluid, but increase progressively in number with increasing age of the rat. The initial population consists of about 90% stage 1 cells and 10% stage 2. Progressive maturation results in successive waves of stage 2 cells during the 2nd week, of stage 3 cells during the 2nd and 3rd weeks, and of stage 4 cells during the 3rd and 4th weeks. These and other results are interpreted to indicate that mast cells in free peritoneal fluid probably arise from free precursor cells rather than by migration from the peritoneal membranes.


Malignant melanoma metastases in the placenta: a case report. Although the coincidence of pregnancy and maternal malignancy is not rare, only 29 cases of metastases to the products of conception have been previously reported and of these, 14 have been of malignant melanoma. The present case of widespread maternal malignant melanoma metastasizing to the placenta further emphasizes this trend. The mother died of malanomatosis two weeks after induced labour at 36 weeks gestation. The infant, despite widespread placental involvement including apparent foetal vascular invasion, is well and without clinical evidence of disease five months after delivery.


Clear cell adenocarcinoma of the uterine cervix: a histological and histochemical study. A case of Mullerian clear cell adenocarcinoma of the uterine cervix occurring in a young women is presented. A detailed histological and histochemical study of this type of tumour is important so as to separate it from the clear cell tumour of mesoenphric origin. The association of Mullerian clear cell adenocarcinoma and other abnormalities of the vagina and cervix with the administration of maternal nonsteroidal oestrogens has been recently stressed in the literature. However, our patient is illustrative of the 30-50% of cases reported to date which have few if any of the associated abnormalities of the genital tract and have no known exposure to non-steroidal oestrogens.


Benign vaginal rhabdomyoma.

Benign vaginal rhabdomyoma. A case of benign polypoid vaginal rhabdomyoma occurring in a 52-year-old female is described. The characteristic histological features were interlacing bands of striated muscle cells with prominent cross and longitudinal striations, with surrounding loose collagenous stroma, within which were many dilated vascular spaces. Electron microscopy confirmed the striated muscle origin of these cells. The pathogenesis is possibly a localized area of abnormal mesenchymal differentiation.


EEG feedback training in the treatment of epilepsy: some questions and some answers. A basic question in EEG feedback training of epileptic patients is whether the decrease in seizures is specifically due to the training or to other factors. Questions may also be raised as to what EEG changes are involved. Preliminary results in five patients suggest that seizure reductions can occur with training which are not due to placebo or nonspecific effects or to changes in medication compliance. These changes occurred rapidly during EEG-contingent feedback training but not when feedback was random in relation to the EEG. Reliable changes in the EEG were also observed, but the question of which mechanism accounts for these results has yet to be answered.


Operant conditioning of the EEG in two patients with epilepsy: methodologic and clinical considerations. Methodologic and clinical considerations are discussed in sensorimotor rhythm (SMR) biofeedback research on two dissimilar but severe epileptic males. The first case, an akinetic epileptic who prior to feedback training experienced 80-100 clinical seizures every 10 hours, showed considerable seizure reduction after 6 months of SMR and epileptiform training. A number of methodologic and instrumentation advances were pioneered with the akinetic patient: (1) development of and ultra-sharp band-pass filter; (2) use of epileptiform inhibit and feedback circuitry; (3) use of monetary rewards as additional incentive; (4) use of correlational analysis for evaluation of acquisition in the major dependent variables and; (5) use of noncontingent feedback and reinforcement as control techniques. The second case, a psychomotor epileptic, also showed therapeutic benefit from SMR training. Clinical information regarding the effect of anticonvulsant medications on the course and therapeutic outcome of SMR training are described. In conjunction with operant conditioning of 12 Hz activity, corresponding changes for other EEG parameters are examined.


Prednisone effects on postnatal brain development of rats following maternal therapy. 16-beta-Metilprednisone was administered in the last week of pregnancy in order to study its effects on postnatal brain development of the litters. Two groups of pregnant inbred rats were used for the experiments. Group I received 1.25 mg/kg/day 16-beta-metilprednisone. Group II served as untreated controls. The litters were killed either within 24 hr after birth, at 17 days, or at 45 days of age. Treated litters (animals whose mothers received the steroid) had a decreased body weight at 17 days of age. Wet brain weight was decreased in the same group. At 17 and 45 days of life treated rats showed a dry brain weight lower than that of controls. Newborn and 17-day-old rats whose mothers received the steroid showed a decreased content of brain proteins. Total lipids, cholesterol, and phospholipids were reduced in the brain of treated rats at 45 days of life. Brain phospholipids were also decreased in 17-day-old rats. These results show that 16-beta-metilprednisone administration to pregnant rats produces long lasting changes in brain chemical composition.


Effect of intermittent phototherapy on bilirubin dynamics in Gunn rats. To determine whether continuous phototherapy is necessary to control neonatal jaundice, groups of jaundiced (Gunn) rats were exposed to four blue light regimens: continuous light, 30 min light/30 min dark, 6 min light/6 min dark, and 6 min light/18 min dark. An exponential decrease in serum bilirubin concentration (SBC) was found with all regimens. A logarithmic dose response curve was obtained with a 50% light dose exhibiting 75% efficacy, and a 25% light dose exhibiting 59% efficacy compared to continuous phototherapy. The time constants of the decrease in serum bilirubin concentration also varied logarithmically with doses with continuous therapy having a time constant of 1.4 days, and 6 min light/18 min dark therapy having a time constant of 3 days.


Glycolytic metabolism of neonatal mononuclear cells. The mononuclear cells of newborn infants compared to those of normal adults contain diminished activity of pyruvate kinase (PK) (14.9 +/- 1.2 vs. 22.3 +/- 1.3 mumol/10(10) cells/min) and phosphoglycerate kinase (PGK) (195 +/- 10 vs. 415 +/- 19). These deficiencies are accentuated in the cells of premature infants (4.9 +/- 0,5 and 71 +/- 15, respectively) and are accompanied by reduced activity of adenylate kinase (AK) (14.8 +/- 1.9 vs. 33.6 +/- 2.6). The activities of AK and PGK in adult and neonatal mononuclear cells are stimulated by phytohemagglutinin (PHA). Although the PK activity of adult cells is stimulated by PHA, the PK activity of neonatal cells is not. Mononuclear cell glycolysis is stimulated by PHA in both adults and neonates. The mean lactate production of neonatal cells is slightly lower than it is in adult cells (93 vs. 110 mumol/10(10) cells/hr, unstimulated, and 151 vs. 181, stimulated), but the differences are not statistically significant. The ATP content of neonatal cells (3.8 +/- 0.4 mumol/ 10(10) cells) is reduced compared to adult values (6.0 +/- 0.3). Lactate production is directly correlated with PK activity in adult and neonatal mononuclear cells. Neonatal mononuclear cell PK activity increases to adult levels during the first year of life.


Acid-base status in dietary treatment of phenylketonuria. Blood acid-base status, serum electrolytes, and urine pH were examined in 64 infants and children with phenylketonuria (PKU) treated with three different low phenylalanine protein hydrolyzates (Aponti, Cymogran, AlbumaidXP) and two synthetic amino acid mixtures (Aminogran, PAM). The formulas caused significant differences in acid-base status, serum potassium, and chloride, and in urine pH. In acid-base balance studies in two patients with PKU, Aponti, PAM, and two modifications of PAM (P2 + P3) were given. We observed a change from mild alkalosis to increasing metabolic acidosis from Aponti (serum bicarbonate 25,8 mval/liter) to P3 (24,0Y, P2 (19, 3) and PAM (17,0). Urine pH decreased and renal net acid excretion increased. In the formulas PAM, P2 and P3 differences in renal net acid excretion correlated with differences in chloride and sulfur contents of the diets and of the urines. New modifications of AlbumaidXP and of PAM, prepared according to our recommendations, showed normal renal net acid excretion (1 mEq/kg/24 hr) in a balance study performed in one patient with PKU and normal acid base status in 20 further patients.


Hereditary mitochondrial myopathy with lactic acidemia, a De Toni-Fanconi-Debré syndrome, and a defective respiratory chain in voluntary striated muscles. A patient suffering froma mitochondrial myopathy leading to severe insufficiency of the voluntary muscles is described. Severe cerebral damage was present. Major biochemical symptoms were extreme lactic acidemia, hypophosphatemia and hyperphosphaturia, and generalized aminoaciduria, renal glucosuria, and polyuria. Muscular insufficiency resulted in lethal asphyxiz. All therapeutic trials were insufficient. The patient and two other children of the same family with a similar clinical picture all died before the 4th month of life. The condition is probably inherited in an autosomal recessive way. A defective respiratory chain in the mitochondria of the striated muscles is proposed as the underlying mechanism. Cytochromes aa3 were absent, b was nearly absent, but cc1 was present. In heart muscle cytochromes aa3 and b were at the level of the controls.


Multiple abnormalities of ectoglycosyltransferases in cultured fibroblasts from patients with mucolipidosis II: Possible indication for abnormal plasma membrane glycoproteins. Ectoglycosyltransferase activities were measured in cultured normal and mucolipidosis II fibroblasts using endogenous glycoproteins and glycolipids and whole cells. Nucleotide pyrophosphatase, known to interfere with glycosyltransferases, was completely inhibited with 6 mM 5' AMP. Since preliminary experiments have shown multiple abnormalities of ectoglycosyltransferases in mucolipidosis II fibroblasts (Di Donato, unpublished results), galactosyl (Gal)-and N-acetylglucosaminyl (GluNac)-transferase were studied in further detail in confluent and nonconfluent cultures of normal and patient fibroblasts. Activities of both transferases on glycoproteins were higher in nonconfluent cultures. A 50% reduced activity of Gal-transferase was measured in confluent mucolipidosis II cultures and of GluNac-transferase in nonconfluent mucolipidosis II cultures towards incorporation of sugar precursors into glycoproteins. Substrate saturation kinetics of both transferases in mucolipidosis II fibroblasts revealed an abnormal Km for Gal incorporation into endogenous glycoproteins. Glycosylation of glycolipids in mucolipidosis fibroblasts was normal.


The T gamma chain of human fetal hemoglobin at birth and in several abnormal hematologic conditions. The T gamma chain of human fetal hemoglobin has a threonyl in stead of an isoleucyl residue in position 75. When the cord bloods from infants from varied ethnic backgrouds and geographic areas were tested for the presence of the T gamma chain, it was present in 28 or 98 samples. In some groups as many as 40% had the T gamma chain whereas none was detected in other. When the T gamma chain was present, its quantity was about 20% of the total gamma chains, but one case had 35%. Among beta-thalassemia homozygotes of the Mediterranean region, 70% and the T gamma chain in the amount of 20-50% of the total gamma chains, but seven Black beta-thalassemia homozygotes were negative for the T gamma chain. The fetal hemoglobin of 16 adult patients with sickle cell anemia had no T gamma chains, but 2 of 9 newborn children with sickle cell anemia had the T gamma chain. The frequency of the T gamma gene (16), the relationship of the T gamma gene to the G gamma and A gamma genes, and the significance of the T gamma gene are discussed.


Hemoglobin synthesis in a rabbit ribosomal system: localization of heme synthetase activity. The activity of heme synthetase (ferrochelatase), the enzyme(s) which catalyzes the formation of heme from iron and protoporphyrin IX, was studied in the various fractions of a cell-free reticulocyte system which synthesizes hemoglobin. The ribosomal fraction contained heme synthetase activity and its characteristics were similar to that described in avian erythrocytes, human and rat liver, and rabbit reticulocytes. It has a pH optimum of 7.5, required sulfhydryl reagents, was denatured by heat and was unstable on freezing. Heme synthetase is a mitochondrial enzyme. Fragments of mitochondrial membrane were identified in the ribosome fraction by both electron microscopy and the presence of cytochrome oxidase activity.


A comparative study of the response to an oral NaCl and NaHCO3 load in newborn preterm and full term infants. Previous recommendations on salt tolerance of newborn infants have mainly been based on knowledge of the capacity of newborn infants to excrete NaCl. Since tolerance to NaHCO3 can hardly be predicted from knowledge of tolerance of NaCl, a comparative study of Na+ excretion following equivalent doses of NaCl and NaHCO3 has been carried out. Forty-nine full term infants aged 0-2 days and 3-7 days were given either an oral load of NaCl or NaHCO3. Ten preterm infants (gestational age 30-35 weeks, postnatal age 2-18 days) were given both NaCl and NaHCO3 after a 2-day interval. The average urinary Na+ excretion 1-5 hr after the load was higher in all full term infants studied, but the difference was significant only in 3-to 7-day-old infants. In 7 of the 10 preterm infants the urinary Na+ excretion was higher following the NaHCO3 load than following the NaCl load. The mean difference between the tests averaged 1 mmol Na+/1.73 m2/hr and was significant. A somewhat higher daily allowance of NaHCO3 (15 mmol/kg/24 hr) than of NaCl (12 mmol/kg/24 hr) is therefore recommended.


Regional lung function studies and radionuclide angiography in D-transposition of the great arteries. Thirty-nine ventilation and perfusion lung studies with xenon 313 were perfomed in 29 patients with D-transposition of the great arteries (DTGA). Fifteen patients had simple DTGA and 14 more complex anatomic features. Inequalitiies of ventilation (V) were present in 23% (9/39) and perfusion (Q) in 44% (17/39) of studies. Six patients with simple DTGA showed abnormal distribution of perfusion, all with increased flow to the right lung. Among the 14 patients with complex DTGA, eight (57%) had abnormal distribution of perfusion. In patients with pulmonary artery band, increased flow was directed toward the left lung, and in those with an aorticopulmonary anastomosis, increased flow was to the side of the shunt. Radionuclide angiograms were performed in 17 patients with DTGA, both before and after surgical repair. In all, an abnormal circulatory pattern was noted. Complete superior vena cava obstruction present in four patients and residual left to right shunt (Qp/qs greater than 1.7/liter) in three was confirmed at cardiac catheterization. Ventilation perfusion studies with xenon-313 and technetium-99m radionuclide angiogram were effective noninvasive techniques in assessing pulmonary function and hemodynamics in patients with DTGA.


Glomerular filtration rate during the period of adaptation to extrauterine life. Inulin clearance (Cin) was measured in 20 infants of 27--43 weeks of gestation during the first 24 hr of their extrauterine life. Cin ranged from 0.7--4.7 ml/min and correlated with gestational age (P less than 0.05). In 18 infants of similar gestational ages studied after 2--3 days of extrauterine adaptation, the Cin ranged from 1.1--17.9 ml/min and also correlated with gestational age (P less than 0.01). By day 2--3, the infants of near term gestational age achieved a greater increase in Cin than did the markedly preterm infants, as reflected by a significantly different slope of the regression line for Cin and gestational age for the infants studied at 1 vs. 2--3 days of age (P less than 0.001).


Human tracheobronchial secretions: development of mucous glycoprotein and lysozyme-secreting systems. Baseline rates for secretion of mucous glycoprotein were similar similar (680--830 microgram/g tissue/24 hour) for cultured tracheal epithelium from newborns of 26--32 weeks' gestation, full term newborns, and older children. Addition of methacholine to culture medium augmented secretory rates of glycoprotein from all tissue sources 3--5 fold. The overall composition of secreted mucous glycoproteins changed little with increasing age. A trend toward less sulfation and toward increased sialic acid and fucose content was noted in secreted glycoproteins from explants of older subjects. Histochemical observations of stored glycoprotein in tracheal tissue, which was subsequently used for organ culture experiments, confirmed that a modest, but consistent sulfate to sialic acid shift occurs during early life. In contrast, baseline secretory rates for lysozyme from tracheal epithelium of preterm infants were one-half as large as rates from epithelium of full term babies and were refractory to cholinergic stimulation. Stimulation of lysozyme secretion by a cholinergic agonist was achieved in all cases by 40 weeks' gestation. We conclude that basal glycoprotein secretion and the mechanism for glycoprotein response to cholinergic stimulation have developed by the earliest age of viability, but that lysozyme secretion is deficient and is unresponsive to cholinergic stimulation in tracheal tissue from preterm newborns.