[Effect of thermal stimulation of the skin on the activity of the cat cutaneous nerve]. Impulse activity of single postganglionic fibres in the sural nerve induced by thermal stimulation of skin of the contralateral hind limb was studied in the cat. The frequency of the impulse activity of these fibres increased in response to cooling and increased or decreased in response to heating= It is supposed that the sural nerve contains not only vasoconstrictive but also vasodilatative fibres


[Selective reduction of the amplitude of the action potentials of neurons in the process of habituation]. Spike discharges of single neurons in the forebrain general cortex of the turtle were recorded extracellularly during habituation to light flashesmthe amplitude of spontaneous spikes, short-latent evoked spikes and spikes after the inhibitory pause was measuredmthe amplitude of short-latent evoked spikes significantly decreased during habtiuation while the background and postinhibitory spikes remained unchanged. It is supposed that the pattern of synapses activated by a definite stimulus may change the state of the elcetrically excitable neuronal membrane during habituation


[Intracellular perfusion of the giant neurons of snails]. The method is developed to perform intracellular perfusion of isolated Helix pomatia neurons. The cell is put under hydrostatic pressure into a pore in the plastic film separting the experimental chamber in two compartmentsmthe lower compartment is perfused with high-potassium solution that destroys the barrier properties of the lower part of the cell membrane. The upper compartment is oerfused with normal Ringer solution and the part of the membrane in contact with it demonstrates usual excitability; Replacement of the high-potassium solution in the lower compartment by a potassium-free one abolished the delayed outward current through the working part of the membrane indicating a free acess of ions to and from its inner surfacemthe investigated membrane maintains its excitability for several hours beeing perfused with the F- and PO4--salts of K+ and Tris


The primary cultures of animal ascites tumor cells growth in tubes in suspension as a model in the screening of antitumor agents. By alternating in vivo-in vitro passage of NK/Ly ascitic tumor cells, a line of tumor cells was achieved which can be used for primary in vitro screening of antitumor compounds. Example is given from testing various known and new compounds.


Effect of D-glucosamine and D-galactosamine on the uridine nucleotide concentration in mouse myeloid tumor (Graffi) and myeloma MOPC-21. The effect of D-glucosamine and D-galactosamine on the content of uridine nucleotides in myeloid tumor (Graffi) and myeloma MOPC-21 of mice was investigated in vivo. After treatment with aminosugars a marked decrease in UTP and UDP-glucose quantity was found. The trapping of uridine phosphates by formation of UDP-sugar derivatives was different in the two tumors and depended on the aminosugar employed. D-glucosamine provoked an increase in the UDP-N-acetylglucosamine pool size in myeloid tumor (Graffi) and myeloma MOPC-21. D-galactosamine administration led to formation of UDP-galactosamine and UDP-N-acetylglucosamine in myeloma MOPC-21, while in myeloid tumor (Graffi) an increase in the content of UDP-N-acetylglucosamine was obtained only.


Macromolecular antitumor agents from Chamaenerium angustifolium. The antineoplastic substances isolated from Chamaenerium angustifolium, Chanerol, a macromolecular polyphenol, and its complex with polysaccharide, Chanerozan, have been studied in vitro in tests of haemagglutination, tumor cell agglutination, leucoagglutination and some others. The results obtained show Chanerol as a new phytohaemagglutinin (lectin) which has no group specificity for human erythrocytes (ABO system). As distinct from other lectins (proteins) Chanerol belongs to another chemical class (macromolecular polyphenols) and has no effect on lymphocytes in leukoagglutination and blast transformation tests. Both preparations have been shown capable of agglutinating tumor cells in vitro and revealed antitumor activity in the intravenous and intraperitoneal administration to mice with transplanted tumors. The toxicity of Chanerozan and its titre of human and mouse erythrocyte agglutination are considerably lower than those of Chanerol. Thus, judging by haemagglutination test Chanerozan behaves as a typical complex of agglutinin with concurrent sugar.


Antiproliferative effect of thymosterin on KB tumor cells in vitro and h 18 R tumor development in the new-born rat. The authors report on preliminary data concerning the antiproliferative activity of thymosterin upon the growth of the KB tumor cells in vitro and in vivo. The experiments in vitro showed an intense antiblastic action of thymosterin, which was proportional to the administered dose. The preliminary results of the in vivo experiments suggest that inhibitory effect of thymosterin on the h 18 R tumor growth in newborn rats.


Antileukemic effect of L-aspartyl-hydrazine. Beta-L-aspartyl-hydrazine can significantly prolong survival of the A mouse strain infected with a lymphatic leukemia sensitive to L-asparaginase. By combining the above substance with L-asparaginase even better results can be obtained.


Morphology of metastatic cancer of the fallopian tube in uterine cervix carcinoma. Morphological examination of 452 Fallopian tubes removed together with the uterus for uterine cervix cancer revealed in 221 patients at the time of operation and in 5 dead on autopsy, metastatic cancer in 8 females (3.5%) in 12 tubes (right-side involvement 2 cases, left-side 2 cases, ambi-lateral 4 instances). In 37 patients there were metastases in inner organs; of these diseased 21.6% were affected by metastatic cancer of the Fallopian tube. Macroscopically, metastatic tumors were of different form in 4 cases; in the remaining instances they were only discovered on microscopical examination. In two cases the tubes were affected in their whole length, in the other case the tumor was located in the ampullary portion. The cyto- and histological structures of the metastatic cancer were the same as those of the primary uterine cervix tumor. The predominating route of tumor dissemination has proved to be lymphogenic propagation (5 cases). In two cases lymphohematogenic dissemination, in one case propagation by implantation were observed.


Value of lymphangiography in the diagnosis and treatment of lymphangioma. On the basis of the author's own results and literary data emphasis is laid on the significance of lymphography for confirming or establishing a diagnosis, for determining the extent of a lesion and for proper considerations on indications for surgical treatment. Relymphography following a surgical intervention is capable of showing whether the latter had been successful and of revealing foci of recurrence. The case history bears on two histologically verified lymphangioma -- in the first case of the soft parts of the right leg, in the second of the soft part of the left thoracic wall, the armpit and the mediastinum. In both cases, relapse after repeated surgical interventions was verified by direct lymphography from superficial lymph vessels of the foot and the cubital fossa.


Iliac lymph nodes as a primary lymph center draining the testicles. The visceral radioisotopic lymphography, as a new technic, reveals new possibilities to investigate the lymph system of the testicle. The testicular lymph center is regularly visualized at the level of the para-aortic lymph nodes. But in 16.9% of the patients, respectively in 10.8% of the examined testes, iliac lymph nodes are demonstrated as a primary lymph center, draining the testicle. A preoperative scintigraphic search can be made for every patient with testicular neoplasma in the intention to obtain a more correct determination of the stage, the prognosis and the proper treatment planning.


Dietary management of patients in chronic renal failure. A new oral amino acid preparation was given to two groups of patients: group 1, five patients on hemodialysis; and group 2, five patients with chronic renal failure (CRF). In group 1 significant pre- and postdiet changes were: BUN 93-37 mg% (p smaller than 0.01); creatinine 13.0-9.7 mg% (p smaller than 0.001); phosphorus 6.6-4.2 mg% (p smaller than 0.05); uric acid 8.7-6.0 mg% (p smaller than 0.01); CO2 16.3-21.3 mEq/I (p smaller than 0.01); hematocrit 18.0-20.8% (p smaller than 0.05). In group 2: BUN 93-66 mg% (p smaller than 0.05); phosphorus 5.6-3.8 mg% (p smaller than 0.05); hematocrit 27.3-30.7% (p smaller than 0.05). Nitrogen balance was positive in all patients. It is concluded that this oral amino acid mixture is well-tolerated and can be utilized in CRF to attain protein anabolism.


Content and distribution of water and electrolytes in maitenance hemodialysis. A group of patients whose dietary potassium was unrestricted and who received 12-18 h of Kiil dialysis twice weekly against a bath containing no potassium, had body potassium concentrations (total body potassium/intracellular volume) of 7.6% lower than normal. Despite marked hypokalemia at the end of dialysis, suprisingly few electrocardiographic changes were seen. Another group of subjects, dialyzed fro 5-6 h thrice weekly against a bath containing 1 mEq/liter of potassium in a Dow dialyzer, showed more marked electrocardiographic abnormalities despite smaller alterations in transmembrane potassium gradients. Rapidity of establishment of potassium gradients is important as well as magnitude. The following changes occur in a single dialysis: 100 mEq of cell potassium and 20 mEq of extracellular potassium leave the body; 100 mEq of extracellular sodium enter the cells and 415 mEq of extracellular sodium leave the body; 3.5 liters of water leave the extracellular fluid, 2.5 liters into the bath and 1 liter into the cells.


Protection against the impairment of renal function after intravascular coagulation in the rat kidney by increased ingestion of sodium chloride. Rats were kept for 4 weeks on a dietary regimen with a low or high sodium intake to increase or reduce, respectively, the renin activity of the kidneys and plasma. Fibrinolysis was inhibited by intravenous injection of AMCA and thrombin was infused into the jugular vein, giving rise to heavy intravascular fibrin deposition in the kidneys. Shortly after the thrombin infusion the glomerular filtration rate (GFR) decreased equally in saline-loaded and normal rats. 48 h after the thrombin infusion the GFR was still markedly reduced in saline-deprived and normal rats but had returned to preinfusion values in the saline-loaded rats. The results might indicate that the renin-angiotensin system is involved in the presistence of the renal functional impairment after intravascular coagulation in the rat kidney.


The influence of ouabain on in vitro renin secretion and intracellular sodium. Renin secretion has been hypothesized to be inversely related to the tubular sodium concentration or load. Using rat kidney cortex slices, in vitro renin secretion was measured as a function of sodium concentration of the medium. We found, as have many others, that renin secretion increases with increasing medium sodium concentration. However, in the presence of 10(-3) M ouabain, renin secretion decreased with increasing medium sodium concentration. We also found that intracellular sodium concentration varied directly with medium sodium both in the presence and absence of ouabain. Furosemide, a known renin stimulator in vivo, had no effect on renin secretion from tissue slices. Although obvious differences exist between in vitro and in vivo results, no simple relationship may exist between intracellular sodium concentration and renin secretion.


Influence of regional factors in the distribution of the histologic patterns of glomerulopathies in the nephrotic syndrome. Analysis of 47 renal biopsies performed on adult patients with nephrotic syndrome in Bahia, Brazil, shows a peculiar distribution of the histologic types with a preponderance of membranoproliferative glomerulonephritis. The possibility of a regional influence is discussed, particularly with regard to Schistosoma mansoni infection which is endemic in this area and probably an important cause of glomerulopathy.


Pseudocyst of the pericardium developing during maintenance hemodialysis. Report of two cases. Two cases of pericardial pseudocyst which developed in the course of maintenance hemodialysis are reported. Both patients were usually free of complaints, although there was evidence of the previous pericarditis with recent accumulation of pericardial effusion. As a possible mechanism leading to pericardial pseudocyst formation, distension of a weak area of the thickened pericardium due to an increase in intrapericardial pressure was assumed. Therefore, pericardial pseudocyst is one of the likely complications of patients on maintenance hemodialysis.


Resistance to acute renal failure afforded by prior renal failure: examination of the role of renal renin content. In this study, rats recovering from glycerol-induced acute renal failure were found to be protected from mercury-induced nephropathy, and HgCl2 poisoning protected rats from developing myohemoglobinuric renal failure. In view of the widely disparate nature of the renal failure models used, refractoriness appears to relate to an altered sensitivity of the organism itself rather than reflecting resistance to a particular nephropathic challenge. Renal renin content of the rats at the time of rechallenge was normal or high, a finding which contrasts sharply with that of chronically saline-loaded animals which also are refractory to ARF but have a maximally suppressed renal renin content. Renal renin depletion is not essential to the prevention of acute renal failure in the rat.


Effects and complications of high efficiency dialysis. Two and three Dow Cordis Hollow Fiber and Gambro Lundia artificial kidneys were used for high efficiency dialysis in large patients, intoxications, and for rapid ultrafiltration. BUN clearances of up to 240 ml/min were achieved. One episode of severe neuropathy occurred during high efficiency dialysis, and hypotensive episodes were more common. High efficiency dialysis has certain indications particularly in intoxication cases. However, because of possible side effects more experience is needed before its ultimate place in the treatment of uremia can be ascertained.


[IgM immunoglobulin in cerebrospinal fluid in cases of multiple sclerosis (preliminary report)]. In cases of multiple sclerosis, central nervous system syphilis and other neurological diseases the IgM was determined in the cerebrospinal fluid by means of radial diffusion. The control group comprised patients with neurosis. It was found that IgM determinations must be done in concentrated fluid when this method is used. Raised total and percent level of IgM in the cerebrospinal fluid was observed in 8 out of 29 cases of multiple sclerosis in the acute phase of the disease.


[Electroencephalographic studies in migraine]. The author reviews the pertinent literature and the results of own investigations in migraine. EEG changes in migraine are observed in nearly 50% of cases during attacks as well as in the periods free of pains. Most investigations were done in the periods between attacks. The H response characteristic of migraine was found by the author in 25% of cases only. Focal changes were present in 30% of cases. They were not related to the side of the pain, its duration and the form of migraine. Seizure activity was never observed. The author regards isolation of the so-called dysrhythmic form of migraine as not justified. EEG changes suggest--according to the author--that migraine is a primary cerebral and only secondarily a vascular disorder.


[Force of femoral abductors in patients with lumbar nucleus pulposus prolapse]. In 50 patients with lumbar nucleus pulposus prolapse the force of femoral abductors was determined by the test of Lovett and by means of dynamometric measurements. In 90% of patients paresis of these muscles was found. A comparison of the incidence of other signs of nerve root damage such as paresis of plantar and dorsal flexion of the foot and toes, sensory impairment on the foot and lack or weakness of ankle jerk showed that paresis of fermoral abductors was most frequent among them. This fact is explained by a particular predisposition for development of uncleus pulposus prolapse at the level of 4th and 5th intervertebral discs with resulting injury to the nerve roots L4, L5, and S1 innervating femoral abductors. The authors think that paresis of femoral abductors may be a pathognomonic sign in the diagnosis of nerve root lesions caused by nucleus prolapse at the levels L4-L5 or L5-S1. The frequency of paresis and the degree of weakness indicate the necessity of motor rehabilitation of this music group in comprehensive treatment of patients with lumbar disc prolapse.


[Rheoencephalographic studies in healthy subjects of various age groups]. The purpose of this study was to establish rheoencephalographic value in 90 healthy subjects aged from 20 to 80 years divided into 3 groups. The investigations were done with a two-channel rheographic apparatus produced by Siemens. The so-called rheography II technique was applied. In each subject measurements were done bilaterally in temporal, parietal and central leads. The curves were evaluated in relation to the ECG curve, taking into account the duration in sec. of two parts of the rheographic curve called I and II intervals. The correlation between the size of intervals I and II and the sex, age, side of measurement and area of measurement was subjected to statistical analysis.


[Usefulness of volumetric studies in the evaluation of respiratory efficiency in nervous system diseases]. In nervous system diseases impairing the efficiency of respiratory muscles the authors determined vital capacity, minute ventilation and respiratory capacity. On the basis of volumetric investigations the authors tried to find an optimal schedule for administration of drugs in myasthenia and determine the usefulness of volumetric and gasometric measurements for the evaluation of respiratory efficiency in neurological diseases.


[Evaluation of anginine in the treatment of cerebrovascular disorders (preliminary report)]. The effect of Anginin was assessed in 10 patients with cerebrovascular diseases. Anginin was administered in daily doses of 1.5 g. during a mean time of 5.25 months. The duration of follow-up before, during and after treatment was 2 years. A favourable effect of Anginin was observed on such symptoms as dizziness, disturbances of recent memory, mental fatiguability, difficulties in concentration and irritability. EEG investigations demonstrated a rise in the index of alpha waves, increased frequency and amplitude of alpha waves, and normalization of tracings in cases with pathological abnormalities. The basic laboratory investigations failed to reveal any significant changes. Side effects included transient dyspeptic symptoms were in 5 patients.


[Sodium nitroprusside in controlled arterial hypotension during neurosurgical operations]. A 0.02% solution of sodium nitroprusside was given in intravenous drip infusion for induction of controlled arterial hypotension during intracranial operations. The drug was given to 9 patients operated upon for aneurysms and 2 patients with intracranial meningiomas. It was observed that arterial blood pressure could be easily controlled in this way for the purposes of operation.


[Complications arising from the use of controlled respiration in patients with neurological diseases]. The authors applied controlled respiration in 112 cases of central nervous system diseases, polyneuropathies and myasthenia. During clinical observation or on autopsy in 30 cases complications were found in the form of subcutaneous and mediastinal emphysema or pneumothorax, narrowing or chondromalacis of the trachea, granuloma formation, decubitus ulcers in the trachea with or without bleeding, and haemorrhagic-ulcerative tracheitis. In 7 cases (6.25%) these complications caused death. Factors leading to complications and their prevention are discussed.


[Importance of intensive therapy in the treatment of severe craniocerebral trauma]. During 10 years 15 085 patients were treated at the surgical department of the County Hospital in Wyszków including 415 cases of severe craniocerebral injury (2.7%). The author stressed and justifies the necessity of organization of intensive therapy and resuscitation units at the admission rooms of county hospitals for maintenance of basic vital functions in severe craniocerebral injury to pass through the critical state and reduce the incidence of mortal complications.


[Recurrent Guillain-Barré syndrome].

[Recurrent Guillain-Barré syndrome]. The author reports a case of recurrent Guillain-Barre syndrome with a period of nearly complete remission during 2 years between acute episodes. The case is reported because of its rarity.


[Chronic bleeding into the syringomyelic cavity (Gower's syringal hemorrhage)]. The authors describe a rare case of chronic bleeding into the syringomyelic cavity treated surgically. Bleeding caused slowly increasing manifestations of disease after 23 years of stationary phase. The cause of such bleedings is unknown.


[Diagnostic and therapeutic difficulties in a case of severe craniocerebral injury caused by an electric injury and a fall]. The authors describe a 37-year-old man suffering electric shock caused by high-voltage current 3 000 Volt. The shock caused a fall with severe craniocerebral injury with fracture of occipital squama and subacute epidural haematoma in the posterior cerebral fossa. The injury was associated with vascular disturbances of the brain and brain stem which caused difficulties in disclosing typical signs of epidural heaematoma. Good therapeutic effects were obtained not only by surgical intervention and also by intensive treatment with antioedematous agents and drugs improving cerebral circulation.


[The painful floating-rib syndrome].

[The painful floating-rib syndrome]. Attention is drawn to a painful syndrome in the front of the chest, due to abnormal mobility of a rib that has lost the normal cartilaginous connection with that above it. The syndrome is common enough, though little understood. Deep, continuous, dull and gravative pain is felt in the bottom of the chest and top of the abdomen, with distribution over the base of the hemithorax involved. It is relieved by rest and exacerbated by the effort and certain postures. One or more ribs on one or both sides may be affected, though the Xth is most commonly concerned. The condition may be the direct or indirect result of trauma, or congenital. Abnormal development of the XIth rib may result in its riding over that above it and so causing pain. The formation of parietal algogenous sites is thought to be primarily responsible for pain. These sites result from rubbing of the end of the free cartilage on neighbouring structures. Direct compression of the corresponding trunk may also be involved. Objective diagnosis is based on topical signs. The floating rib is readily recognised as the cause of pain and the syndrome itself is known as the painful slipped (better, floating) rib syndrome. Satisfactory results are obtained by deep analgesic infiltration at the end of the free cartilage and can be prolonged by rest. Reference is made to previously reported data concerning functional disorders of the extrahepatic bile ducts in subjects with this syndrome in the light of a more ample case series. The radiological picture is usually marked by gall bladder hypertonia and hyperkinesis, with occasional sphincter involvement. The physiopathogenetic interpretation of these associated parietobiliary manifestations is discussed in the light of experimental and therapeutic evidence. Their clinical interest is also stressed.


[Comparison of the antibacterial activity in vitro of a combination of penicillin and other antibiotics on 127 strains isolated in an Oncological Institute]. 127 pathogenic, opportunist and saprophytic strains isolated from patients and material in a Milanese oncological department were tested. An association of Ampicillin and Dicloxacillin ana (Diamplicil) proved effective against all strains, particularly Gram-negative bacteria notoriously responsible for hospital infections. A statistically inferior performance was observed for Rifampicin and Cephaloridine.


Neuroendocrine dysfunction in galactorrhea-amenorrhea after oral contraceptive use. Nonpuerperal  alactorrhea and amenorrhea have been reported following the use of oral contraceptives. Treatment of this condition with ergot alkaloids has proved to be of great therapeutic value. Pretreatment plasma hLH and hFSH concentrations in 13 women with postqill galactorrhea-amenorrhea (PPGA) were 6.6 plus or minus 0.6 (SE.) and 5.0 plus or minus 0.8 mlU/ml, respectively. The mean prolactin concentration was 80.7 plus or minus 13.2 ng/ml. After complete evaluation in which diagnostic evidence of pituitary tumor was absent, the patients were treated with ergocryptine (CB-154). The mean hPRL concentration at 14 days of therapy was 7.8 p;us or minus 1.9 ng/ml. Cyclic gonadotropin secretion resumed in all but one instance; ovulation was confirmed on the basis of a biphasic temperature chart and in 5 cases, endometrial biopsy. Measurement of serum dopamine-beta-hydroxylase (DBH) activity indicated a significant decline at the end of 8 weeks of CB-154 therapy. The fall in hPRL was not necessarily associated with a fall in DBH. The majority of women in this study exhibited a consistent personality suggesting varying degrees of anxiety unrelated to the PPGA  and usually antedating the use of oral contraceptives. PPGA was found in women without hyperprolactinemia, but altered hPRL secretion was evident in all instances. The data suggest that the disorder of cyclic gonadotropin secretion is related to altered hPRL secretion, but the mechanism is possibly related to a catecholamine abnormality. The data support the presence of an inherent cyclic mechanism for the secretion of gonadotropins. CB-154 therapy does not affect conception, and no teratogenic effects were observed in 2 infants born to  women who had received CB-154 during the first 40 days of gestation.


Nonpuerperal breast secretion. Its relation to the use of oral contracetpives. The occurrence of breast secretion more than 1 year postpartum was studied in 800 healthy, parous women of childbearing age. Among of 418 women who were using a combination-type oral steroid contraceptive, the incidence of breast secretion was lower than among the nonusers. The incidence of bilateral secretion decreased with increasing duration of use of the oral contraceptives. Statistical material is presented for the incidence of breast secretion as related to age. time elapsed since last delivery, and duration of nursing the last child. Brownish secretion rather than white or yellowish is seen more often in women over 30 years of age. Various menstrual irregularities (excluding amenorrhea) do not appear to be associated with an increased incidence of breast secretion.


Ovarian hyperstimulation syndrome.

Ovarian hyperstimulation syndrome. Eighteen patients hospitalized for excessive ovarian hyperstimulation syndrome are reported. In 14 cases the ovarian hyperstimulation was induced by human menopausal -onadotropins and in 4 cases by combined treatment with clomiphene and HCG. In 5 patients the hyperstimulation was associated with conception, which resulted in 1 quintuplet delivery, 1 early quintuplet abortion, 1 twin abortion, 1 normal delivery, and  1 missed abortion. The regimen of treatment was a conservative one. The patients were hospitalized and treated with infusion of plasma expanders. Anticoagulant therapy was administered only in cases that showed clinical evidence of thromboembolic pheomena or laboratory evidence of severe hemoconcentration. The pathogenesis of the ovarian hyperstimulation syndrome, prevention, and management are discussed. This syndrome should be diagnosed early and treated intensively.


Micronized 17 beta-estradiol for oral estrogen therapy in menopausal women. Micronized 17beta-estradiol (E2) was used as oral replacement therapy in 369 patients with estrogen deficiency and related menopausal symptoms. Over 95 percent of 319 patients evaluable for efficacy gained satisfactory relief of their symptoms from cyclic (on 21 days/off 7 days) E2 therapy. Approximately 77 percent required no adjustment of their initial daily dose, viz, 1 mg (5 or less hot flushes per day) or 2 mg (6 or more flushes daily). In addition, 80 percent (58/72) of the patents who did not obtain adequate control from their starting dose were successfully titrated, either upward to a maximum of 4 mg/day or downward for maintenance. Overall, a higher percentage of patients were treated successfully with 2 mg daily (209/319; 66 percent) than with 1 mg/day (22 percent). About 8 percent of the patients required 3 or 4 mg daily, while 4 percent failed to derive adequate benefit from micronized E2. Oral E2 therapy was well tolerated; hence, the attrition rate due to side effects or lack of control was only 6 percent (22/369). Moreover, all laboratory fingings were within normal limits, even in patients treated with E2 for over 12 months. Coincidental endometrial changes were found in 9 patients, all of whom had received long-term (9 months-3 years) estrogen therapy prior to entering this study. Thus, the stste of the endometrium should be determined before any estrogens are given for the monopause. It is concluded that micronized E2 is highly efficacious, well accepted, and safe for oral estrogen-replacement therapy in menopausal women.


Open cuff method of abdominal hysterectomy. An open cuff technic was employed in 2421 consecutive patients with total abdominal hysterectomy. Extraperitoneal drainage was purpose of the method. The two most serious complications were postoperative hemorrhage (7 cases, 0.28 percent) and intestinal obstruction (6 cases, 0.24 percent). The morbidity rate was 20.8 percent. Of those without colporrhaphy (two-thirds), the morbidity rate was 18.2 percent. Prophylactic antibiotics were not used in the latter group. In no instance was a pelvic abscess or cluff abscess recognized. Death occurred in 1 case (0.041 percent). This method may diminish the occurrence of apical infections above a closed vagina by allowing immediate extraperitoneal drainage. Postoperative bleeding and intestinal obstruction, along with other rare conditions, continue to represent occasional but severe complicantions.


Pregnancy performance of patients under fifteen years of age. Pregnancy performance of 471 patients under age 15 who delivered between 1968 and 1972 was compared with that of the same number of control patients between 19 and 25 years of age. The control group was selected by the paired method technic, whereby each study patient was paired with a control patients utilizing identical race and contribution to hospital cost as the economic determinant. The results of the study showed that young patients differed significantly from the control group in having an earlier menarche and a greater number of recurring pregnancies within 18 months of the initial one. Pregnancy-induced hypertension and pelvic inlet contraction were pregnancy complications occurring more frequently among study patients than control patients.


Interlocking twins. Experience with four cases and suggested management. Experience with the management of 4 pairs of locked twins is described and analyzed. In view of the high morbidity figures a proposed preemptive management is suggested.


Fetal cardiac interval recorder.

Fetal cardiac interval recorder. A recorder is described which is capable of continuously measuring intervals between two events of the fetal cardiac cycle, as well as functioning as a routine intrapartum monitor. We have primarily measured the interval between the R wave of the fetal ECG  and the second fetal heart sound (R-S2), but the recorder is also capable of measuring R-R, R-A0 (opening of aortic valve), R-Pl (placenta), and R-Sc (scalp) intervals. In the discussion, we endeavor to show that these intervals reflect fetal cardiac performance, which is altered by drugs and acidemia.


Amniotic fluid components as determinants of fetal maturity. In order to evaluate the most reliable means of determining fetal maturity, six amniotic fluid components were analyzed from 99 women who were 22 to 40 weeks pregnant. The six parameters investigated were: amylase activity the lecithin to sphingomyelin (L/S) ratio, percentage of fat cells, and the concentrations of protein, creatinine, and bilrubin. In general, single components and combinations of two or three of the tests did not significantly enhance the predictive accuracy or reduce the error from that obtained with the L/S ratio used alone.


Prognostic parameters and clinical staging criteria in the epidermoid carcinoma of the vulva. An evaluation and a critique of prognostic parameters and criteria involved in the classification and clinical staging of epidermoid carcinoma of the vulva are presented, comparing the FIGO system and a proposed more definitive system. Biostatistical as well as clinical evidence for an improved system is presented. The proposed system is based on statistically valid data, has good patient distribution, and an orderly progression for therapy and prognosis. In addition, it is well suited for computer programming and for the comparison of patients and therapy, as well as for delineating the natural history of vulvar cancer.


Role of needle aspiration biopsy in diagnosis of carcinoma of the breast. Needle aspiration of a breast mass, a procedure widely employed in Scandinavia but neglected in the United States, has an imporant role in the diagnosis of carcinoma of the breat. Five hundred and ninety-seven patients has aspirations from 706 lesions, 415 solid and 291 cystic. There were 83 malignancies, with abnormal cells in 73. In the majority the diagnosis could be made readily. There is no known contraindication to the procedure. Aspiration at the initial visit may alert the physician to malignancy, thus avoiding undue delay in treatment.


Feminization in gonadal dysgenesis associated with ovarian gonadoblastoma. A case of gonadal dysgenesis in a phenotypic female with XY genotype associated with ovarian gonadoblastoma is reported. Endocrinologic studies suggest that the normal female secondary sex characteristics could be due to estrogen production from luteal intersitial cells.


Puerperal myocardiopathy complicating stimulataneous uterine and tubal pregnancies. The authors point out the difficulty in recognizing puerperal myocardiopathy and the necessity for standardizing the diagnostic features. The patient described here was all the more unusual because of the coincidental occurrence of a second rare condition-simultaneous uterine and tubal pregnancies. Our data may add support to the theory that all ill-defined myocardial lesion resblts from an autoimmune response.


Basal cell carcinoma of the vulva.

Basal cell carcinoma of the vulva. A clinical and histopathologic study of material from a series of 17 patients with basal cell carcinoma of the vulva are reviewed. The tumors occurred primarily in elderly patients (average age, 59 years), the majority of whom were Causasian. Presenting symptomatology consisted primarily of pruritus vulvae and/or the presence of a vulvar mass (79%) of long duration (average, 6 years, 7 months). The lesions were described grossly as ulcerations or masses located on the anterior labium majus. Etiologies were indeterminate although 2 patients had previously received vulvar irradiation. Therapy consisted primarily of wide local excision and was effective in that follow-up studies in 16 patients revealed no deaths attributable to basal cell carcinoma. These data indicate that basal cell carcinoma is a locally invasive nonmetastasizing tumor best treated by wide local excision providing the tumor edge does not extend to the margin of excision.


Conization as treatment  of carcinoma in situ of the uterine cervix. A series of 343 consecutive cases with the preoperative diagnosis of carcinoma in situ of the uterine cervix treated by cervical conization is presented. In 93% of these patients cervical cytology returned to normal. The follow-up period ranged from 1 to 5 years. There was significantly greater chance for an apparent cure in cases in which histologic evaluation indicated free margins of resection (98%) than in those where the margins were involved by the neoplastic process (70%). Colposcopic evaluation to determine the site for punch biopsies and adequate resection margins could greatly enhance the success of therapeutic conization. The urgent need for conservative management of cervical intraepithelial neoplasia because of its predominance among young women is discussed.


Diagnostic outpatient aspiration curettage. Outpatient uterine curettage has proved to be an effective diagnostic tool and could replace the need for many hospital curettages. The materials needed to perform an outpatient curettage are described. The method was evaluated on 300 patients who underwent conventional hospital curettage under anesthesia 24 hours after the outpatient curettage. The outpatient curettage was evaluated for safety, reliability, economy, effectiveness, and patient acceptance. The results of the two methods compared favorably.


Use of medroxyprogesterone acetate to prevent menopausal symptoms. A number of patients with severe vasomotor symptoms of menopause, specifically hot flashes, are unable to take exogenous estrogens because of intolerance of contraindications. Others achieve less than satisfactory relief of symptoms with extrogen. A double-blind study was established to determine whether depomedroxyprogesterone acetate (DMPA) injectable (Depo-Provera, Upjohn) could be used as a satisfactory substitute in these patients. The basis of the study was to evaluate clinical impressions that some menopausal patients taking DMPA for other purposes achieved relief from these distressing symptoms. Fifty-seven patients were treated with DMPA, 150 mg IM monthly, and 12 controls were given 1.5 ml sterile saline IM monthly. Serum FSH and LH were measured initially and serially. Clinical response was determined by the patients' estimates of the frequency and severity of their hot flashes. Of 57 patients in the treatment group, 51 (89.5%) were relieved of symptoms compared to 3 of 12 (25%) in the control group. DMPA can be an effective alternate to estrogen therapy in selected menopausal patients.


Routine electronic monitoring of fetal heart rate and uterine activity during labor. Routine electronic monitoring has been performed on 2411 labor patients at Booth Memorial Medical Center. Most recently, 88% of all patients delivered were monitored. As a direct result of this program, intrapartum stillbirths have been dramatically reduced from 1.2/1000 livebirths to 0.5/1000 livebirths. Perinatal mortality for fetuses over 1000 g has fallen to 8.8/1000 deliveries. Apgar scores below 6 at 5 minutes have decreased from a rate of 24/1000 to 14/1000 livebirths. No increase in cesarean sections for fetal distress has occurred although the primary cesarean section rate has increased over the past 10 years, apparently unrelated to fetal monitoring. It is strongly recommended that all patients in labor be monitored by currently available technics.


Fetal renal malformation following treatment of Hodgkin's disease during pregnancy. A case of human fetal renal maldevelopment following the administration of nitrogen mustard, vincristine, procarbazine, and prednisone in early pregnancy for therapy of Hodgkin's disease is reported. While these agents have been shown to be teratogenic in animal experiments, adverse fetal effects following their use during early human pregnancy have not been described. In spite of this previous experience, it has generally been recommended that these agents be withheld during the first trimester of pregnancy because of their presumed teratogenic potential. This case would seem to reinforce this recommendation.


Human placental lactogen levels during and after labor. In order to estimate the human placental lactogen (HPL) level and its value as an indicator of fetoplacental function during labor, we determined HPL levels (N equals 225) before, during, and after labor in normal (N equals 16) and preeclamptic (N equals 14) subjects or in patients with benign intrahepatic cholestasis of pregnancy (N equals 5). During labor, greater decreases in this value were found in preeclamptic than in normal subjects and similarly in mothers with fetoplacental dysfunction than with normal fetoplacental function. The rupture of the membranes had no effect on the level of HPL, which was not related to parity, oxytocin infusion, time interval from rupture of the membranes to delivery, nor to relative placental weight. The half-life of HPL varied in the range of 20-23 minutes immediately after delivery and in the range of 30-39 minutes some time later. During labor, greater decreases in HPL level in cases of preeclampsia or fetoplacental dysfunction may be caused by relative uteroplacental ischemia during uterine contractions, but from this finding it is hard to expect any advantage of HPL as a monitor of fetoplacental function during labor.


Cardiovascular effects of oxytocin.

Cardiovascular effects of oxytocin. Oxytocin, 5 to 10 units, is frequently given as a bolus injection following term delivery or elective termination of pregnancy. It is not general knowledge that this has any untoward effects. In the present study in young, healthy women undergoing elective termination of pregnancy, mean arterial blood pressure decreased approximately 30% and the total peripheral resistence 50%, 40 seconds after injection. However, heart rate increased 30% and stroke volume 25%, so that the cardiac output was elevated more than 50% above control. Oxytocin given as a dilute solution produced no circulatory change; hence, we suggest that this drug be administered in such fashion rather than by bolus injection.


Smallpox vaccination during pregnancy.

Smallpox vaccination during pregnancy. The obstetric outcome (abortions, stillbirths, prematurity, mature births, and congenital abnormalities) in a group of 1522 consecutive pregnant patients who had smallpox vaccinations during recent pregnancies was compared to that in a similar control group of 2024 consecutive pregnant patients who did not receive any antenatal vaccination. Results showed that smallpox vaccination during pregnancy did not increase the rate of stillbirths, premature births, or congenital abnormalities in patients who had been vaccinated at least once before. However, it was noted that women vaccinated during the first trimester of pregnancy more often had children with clubfoot. Therefore, unless there is an immediate risk, we recommend delaying smallpox vaccination during pregnancy until the second or third trimester. However, during epidemic, vaccination should be done regardless of gestational age.


Complete vaginal occlusion in postmenopausal women. The spontaneous development of total vaginal occlusion as the result of postmenopausal atrophy is unusual. This poorly described entity may give rise to diagnostic confusion, as the site of vaginal occlusion resembles an atrophic cervix flush with the top of a stenotic vaginal vault. Fluid collections above this site of occlusion may produce pelvic masses with a characteristic physical sign. The absence of any history of vaginal injury or disease distinguishes these cases from other types of acquired vaginal occlusion.


Current trends in ophthalmic anesthesia. The Second Walter S. Atkinson Lecture. General anesthesia permits surgery involving large operative fields without limit to time. It is essential in children and uncooperative adults and provides an immobile, quiet patient who does not recall the operative procedure. Local and regional anesthesia re indicated when the surgical field is limited in size and extent. Neuroleptanesthesia in ophthalmology usually involves the administration of droperidol followed by fentanyl followed in intubation, sometimes using a muscle relaxant, and maintenance of anesthesia with nitrous oxide. The terrifying dreams produced by ketamine may be minimized by preoperative administration of diazepam and a quiet recovery period. Attempts to eliminate the oculocardiac reflex are unpredictable and unreliable and, with careful monitoring of anesthesia, elimination does not seem essential. Malignant hyperthermia is an autosomal dominant disorder occurring mainly with the administration of halogenated fluoroethane and depolarizing muscle relaxants. It is often signaled by sudden and prolonged muscle spasm following the injection of the muscle relaxant. Treatment must be directed toward hyperventilation using oxygen, correction of the metabolic respiratory acidosis, and reduction of fever.


Melanoma of the iris: report of 72 cases treated surgically. Seventy-two cases of malignant melanoma of the iris treated surgically have been reviewed from Wilmer Institute records with respect to the age, sex, and race of the patients and the clinical and histologic results. Clinical features studied include location and extent of tumor, duration, presence of preexisting lesions, and associated features such as hyphema, glaucoma, cataract, pupillary distortion, and vascularity of the tumor. Surgical therapy included iridectomy, iridocyclectomy and enucleation. Complications of iridectomy included cases of hyphema, cataract, wound dehiscence and episcleral seeding of the tumor. Complications of iridocyclectomy included cases of vitreous loss, cataract, high astigmatism and incomplete excision. Histopathologic features were studied, and the relationship of cell type and tumor cohesiveness to tumor behavior was stressed. Tumor deaths were observed in two of the 72 cases. Clinicopathologic and statistical features in this series of 72 patients were compared with those previously reported series of iris melanomas, and the therapy of these lesions was discussed.


Surgical treatment of exotropia after surgically produced pseudoparalysis of the medial rectus muscle. The characteristic clinical findings of pseudoparalysis of the medial rectus muscle include exotropia in primary position, widened medial fissure on the affected side, limitation of adduction on the affected side, an A-pattern exotropia, and a paradoxical forced-traction test. We have devised a surgical technique to restore good movement of the eye in adduction. The priniciple behind the technique is that all adhesions between Tenon's capsule covering the muscle and conjunctiva, and between muscle and sclera must be found and cut posterior to the fornix. This will allow the muscle to be brought forward easily so that it can be resected and advanced for restoration of function.


Dacryocystorhinostomy with nasolacrimal duct prostesis. For many years the standard surgical treatment for chronic dacryocystitis has been the anastomosis of the lacrimal sac mucosa to nasal mucosa over the margins of an ostium through the lacrimal bone. Failures of this standard procedure have been attributed to many factors and complications frequently require reoperation. The procedure described in this paper was developed as one means of overcoming some of these difficulties. It consists of the implantation of a specially shaped nasolacrimal duct prosthesis from the base of the sac through the interosseous canal into the inferior nasal meatus. This procedure gives reasonable assurance of permanent drainage and is recommended as a primary procedure of choice. The operation is described.


Vitrectomy from the anterior approach. Vitrectomy for the anterior segment surgeon. There are three basic needs for a vitrector or vitreophage. One is for the anterior segment surgeon so that he may have a machine available when vitreous is lost during anterior segment surgery and may spare himself the hazards and potential complications of doing vitrectomy solely with cellulose sponges. The simplified vitrector which is disposable, sterile, and rapidly made ready ideally serves this need in a way which is not served by any other technique. Two, the removal of normal vitreous may be necessary in patients with vitreous contact, and any type of vitreous removing machine may be useful for this. The vitrector we have worked with is simple and satisfactory, and has the potential advantage of having blades which are always sharp and always pushed firmly against the cutting edge of the hole since they are disposable and inexpensive. An infusor as well as simple cutting tips are available. Three, vitrectomy for serious vitreous pathology can be done with the simple vitrector through the anterior segment approach if the lens is absent or will be removed, and if heavy pre-retinal and vitreous bands are not present. For the handling of diabetic retinopathy and sheets of vitreous membranes which appear organized, other equipment may be superior.


Aphakic retinal detachment.

Aphakic retinal detachment. An analysis of 54 cases of ARD, and a PRD control group, revealed that retraction of the posterior vitreous hyaloid was more severe in the aphakic eyes. On the basis of retinal break morphology, the ARD cases could be divided into two groups: (1) detachments that had resulted from small tears situated along the posterior slope of a peripheral retinal traction ridge and (2) detachments that had resulted from breaks that resembled those encountered in the PRD group. The yearly incidence of retinal detachment, in the 38 and over age group, was calculated to be 12 times greater for an aphakic eye. That increase in risk was thought to be due to the changes in vitreous morphology which follow cataract extraction.


[Generalized sarcoidosis with brain and eye participation]. A 34-year-old patient was treated four weeks before his death for a recurrent binocular iritis. He died with clinical symptoms of a cerebral respiratory paresis. The diagnosis of epithilial cells sarcoidosis was made only after histological post mortem examination. It was a cerebral form of chronic disseminated encephalomeningitis with a vascular component. Typical granulomes were found in several organs and also in conjunctiva, ciliary body, choroid and optic nerve.


Color angiography and angioscopy.

Color angiography and angioscopy. The authors present the results of their color fluorescein angiographies carried out with a pocket retinograph equipped with new interferential filters. After the graphic examination, they propose to use these same filters mounted on different instruments for binocular and monocular angioscopy. Their results show that retinal vessels are translucid and that their color changes according to their background. The authors termed this change 'versicolored effect'. Moreover, color angiography with these new filters eliminates pseudofluorescence and adds to the fluoroscopic examination an element of analytic perfection, thus giving a new opening to differential diagnosis in endo-ocular diseases.


Effect of calcium bodesilate (doxium) on circulatory disorders of the retina with special emphasis on diabetic retinopathy. The authors examined the effect of calcium dobesilate (Doxium ¿) on 85 subjects with diabetic retinopathy, occlusion of the central vein of the retina and other retinopathies of vascular origin. Capillary resistance measured on the skin and conjunctiva showed, as compared with 100 healthy subjects, a significant decrease. The efficacy of long-term treatment with Doxium was highly significant in restoring CR to normal. Visual acuity improved in 45.8% of simple DR cases, and became stabilized in 27.5% of cases with malignant DR. Hyperpermeability of retinal vessels decreased in 60% of simple DR cases. It is pointed out that glaucoma did not develop in cases of venous occlusion and the diagnostic value of capillary resistance measurement in diabetes. As a highly effective vasoprotective drug, Doxium¿ is the treatment of choice in all retinopathies of vascular etiology.


[Adaptometry and static perimetry in the early postoperative period following an operation for detached retina]. A group of 62 patients were examined for the adaptometry curve and the static central field in the early postoperative period following an operation for detached retina by various techniques. Comment is made of the data obtained with reference to extension of the detachment, reoperated cases, and results in general.


Wound healing after xenon arc photocoagulation in the rabbit retina. Identification of the proliferating cells in the lesion by light and electron microscopic autoradiography using 3h-tymidine. Processes of the scar formation after Xenon arc photocoagulation in the rabbit retina were studied. Electron microscopic autoradiography using tritiated thymidine identified the proliferating cells in the reparative tissue as Müller's cell, retinal pigment epithelial cell, and choroidal fibroblast. The Müller cell and the retinal pigment epithelial cell, which proliferated in and around the lesion, formed the retinal scar tissue, while the proliferated fibroblast in the choroid did not participate in the formation of the retinal scar. The Müller cells extended their cytoplasmic processes toward the pigment epithelium to form the interdigitating adhesion. This process seemed to be secondary step of the scar formation following the cell proliferation. Migration of cells from the edge of the lesion into the damaged retina seemed to be also a secondary step after the proliferation. Phagocytic activities to engulf the retinal debris were observed in Müller's cells and the retinal pigment epithelial cells. Whether or not astrocytes in the retina do proliferate and are involved in the scar formation after the photocoagulation still remains unanswered. Electron microscopic autoradiography using tritiated thymidine after photocoagulation in the monkey retina might answer the question.


[Langerhans granules in epitheliomas of the eyelids]. In eyelid epitheloimata: basaliomata, spinaliomata and warts very numerous Langerhans granules were found in Langerhans cells


[Does a correlation exist between Myambutol dosage and occurrence of optic neuritis]. The frequency of retrobulbar neuritis during a long lasting myambutol therapy increases proportionally with the increased doses. This may be seen in retrospection on 2007 cases divided into 16 groups with doses from 15 till 60 mg per kg of bodyweight. Graphically a function may be established between myambutol doses and frequency of optic neuritis (y = -23.2 + 1.1 x). This shows for 20 mg/kg: 0%, for 25 mg/kg: 5%, for 30 mg/kg: 10% frequency of optic neuritis. Those findings allow a rough evaluation of neuritis risk and confirm clinical observations. A planed examination of patients groups with different myambutol doses checked by myambutol serum levels estimations would help in establishing optimal doses of myambutol.


Influence of body position on the intraocular pressure of normal and glaucomatous eyes. In 77 normal and 65 glaucomatous eyes the influence of body position on the intraocular pressure was studied, using the pneumatonograph. The pressure increment when changing from the seated to the supine position averaged 2.9 mm Hg in normal eyes and 3.9 mm Hg in glaucomatous eyes. The pressure increase occurred immediately upon lying down and was reversible after returning to the seated position. Comparative measurements with the Goldman tonometer in the seated position showed good agreement with the results obtained by the pneumatonograph. The Schiotz tonometer did not reliably reveal the true supine intraocular pressure. The postural response (seated to supine) showed considerable variation in individual normal and glaucomatous eyes, and it did not correlate consistently with the intraocular pressure in the seated position. It should be taken into account that the results in the glaucomatous eyes were obtained while the patients were on glaucoma medication. In a series of six lowtension glaucomatous eyes the postural response was significant as a probable pathogenetic factor in that disease, because the intraocular pressure could rise from a normal to a glaucomatous level upon changing from the seated to the supine position.


Pump infusion of pilocarpine.

Pump infusion of pilocarpine. Pilocarpine was infused into the conjunctival sac of glaucoma patients with the Sage Model 216 pump. Doses as high as 20 mg were given in 30 min without ocular or systemic toxicity. The ocular hypotension effect, in the same group of patients, was doubled over 4-percent pilocarpine drops given four times daily. In addition to increased efficacy the duration of the ocuoar hypotensive effect was markedly prolonged. Return of ocular pressure to baseline values after a single pump infusion of 20 mg required an average of 33.9 h.


Investigations into the aqueous humour dynamics in primary pigmentary degeneration of the retina. 40 patients with primary pigmentary degeneration of the retina were investigated for the possible coexistence with glaucoma. 12.5% established primary glaucoma cases and 7.5% suspicious glaucoma cases were found. In primary pigmentary degeneration of the retina with no glaucoma the intraocular pressure and the parameters of Leydhecker's test showed the same distribution as that of the controls selected at random. The intraocular pressure and the tonographic parameters except for CL3-7 were slightly lower on the average in the group with retinitis pigmentosa than in the controls.


Aminonitriles: possible role in chemical evolution. The formation of HCN, ammonium cyanide, alkylnitriles, aminoacetonitrile and its C- and N-methyl homologs was demonstrated earlier in a simulated Jovian atmosphere. The polymeric material resulting in these experiments was shown to give glycine, alanine, sarcosine, aspacrtic acid and some imino dibasic acids on acid hydrolysis suggesting thereby the participation of the monomeric nitriles into the formation of the polymeric product(s). Further examination of products resulting from semi-corona and arc discharge through a mixture of methane and ammonia has provided evidence for the formation of alkylaminopropionitriles as a complex mixture and also some pyridyl and pyrimidyl type heterocyclic compounds. A GC-MS examination of the heterocylics showed resemblance with those found in some carbonaceous chondrites. The significance of these findings in relation to chemical evolution will be discussed.


NMR studies of prebiotic polypertides.

NMR studies of prebiotic polypertides. Several polypeptides prepared by means of pyrocondensation have been the subject of structural investigations. Attention has been focused on the constitutional characterization of homo-and co-polymers containing Asp and Glu residues, whose role is essential for the formation of the so-called proteinoids. Contrary to the literature data based on chemical degradation, nmr studies show conclusively that in thermal poly-aspartic acid only beta-peptide linkages are present. This result casts serious doubt on the role thermal condensation might have played in prebiotic polypeptide syntheses.


Molten earth and the origin of prebiological molecules. Evidence for the molten Earth at its accretion time has been accumulated through the geochemical investigations and the observations of the surfaces of planets by space probes such as Venera 8, Mariner 9, Surveyor, Luna, and Apollo. The primitive terrestrial atmosphere might have been derived from the volcanic gases, as suggested by Rubey, but of a higher temperature than so far assumed. A thermochemical calculation of the composition of the volcanic gas suggests the following possibilities: (1) Large amounts of H2 and CO were present in the primitive atmosphere. This gives a theoretical basis for the HCN-production experiment by Abelson. (2) HCHO and NH3 existed in the primitive oceans, of the amount comparable with the weight of the present biosphere. (3) Plenty of NO3-, SO4, and PO4 were expected in the primitive oceans. The NO3- ions might have been useful for the nitrate respiration advocated by Egami. In an appendix, it is argued, on ;he basis of the observational evidence of the exospheric temperatures of planets by space probes, that a highly reducing atmosphere would (if it existed on the primitive Earth) have disappeared very quickly due to the thermal escape of hydrogen from its exosphere.


A technique for the determination of enantiomeric amino acids in biological samples. Racemic amino acids can be separated into their enantiomers by means of gas-liquid chromatography. The most applied technique, today, is the conversion of chiral compunds into diastereoisomers with optically active reagents and subsequent chromatography on conventional optically inactive stationary phases. In previous studies it has been realized that this technique is associated with various problems. We studied the use of optically active stationary phases for separating enantiomers directly via a diastereoisomeric association complex. The optically acitve stationary phases employed are N- and C-terminal substituted dipeptides of the type N-trifluoroacetyl-dipeptide-cyclohexyl esters and have been synthesised by the I-hydroxibenztriazole dicyclohexylcarbodiimide method. The quality of these phases with respect to separation factors, resolution factors, and thermodynamical properties have been evaluated. All synthetic phases show excellent properties; however, when attempting separation of mixtures of naturally occurring amino acids extensive overlap in the elution diagram was detected. Only one phase - N-TFA-L-chi-amino-n-butyryl-L-chi-amino butyric acid cyclohexyl ester - gave complete resolution of the naturally occurring amino acids alanine, valine, glycine, threonine, leucine, isoleucine, serine and proline on a 400 ft x 0.02 in capillary column. Less volatile amino acids such as aspartic acid, phenylalanine, methionine, glutamic acid, tyrosine, arginine, and tryptophan can be resolved at a 100 ft x 0.02 in column.


Evolution in bioids: hypercompetitivity as a source of bistability and a possible role of metal complexes as prenucleoprotic mediators of molecular asymmetry. Spontaneous production of optically active compounds can occur through kinetic instability of an asymmetric steady state in open systems, in which two enantiomeric autocatalysts compete for a common prochiral substrate in a stereoselective reaction of order n greater than 2. For the case of n=3, a proof of instability of a symmetric reacting state in the general case, and functions of reaction parameters ('Chemical Reynolds Numbers') governing the existence and stability of 7 different steady states are derived. The 'extinct state' (without autocatalyst) is stable; a finite amount of products is required to shift it into one of the reacting steady states. A mutation from one state into another in such system ('bioids') involves an amplification of different 'kinds of information', as 'stochastic' (noise into dissipative structures), 'molecular' (autocatalysts), and 'stoichimetric' information. Stereospecific third order kinetics are believed to be realizable on octahedral metal complexes with two-dentated ligands and to have played a role in the prebiological evolution of optically active compounds.


Entropy of the genetic information and evolution. The entropy of the amino acid sequences coded by DNA is considered as a measure of diversity of variety of proteins, and is taken as a measure of evolution. The DNA or m-RNA sequence is considered as a stationary second-order Markov chain composed of four kinds of bases. Because of the biased nature of the genetic code table, increase of entropy of amino acid sequences is possible with biased nucleotide sequence. Thus the biased DNA base composition and the extreme rarity of the base doublet CpG of higher organisms are explained. It is expected that the amino acid composition was highly biased at the days of the origin of the genetic code table, and the more frequent amino acids have tended to get rarer, and the rarer ones more frequent. This tendency is observed in the evolution of hemoglobin, cytochrome C, fibrinopeptide, immunoglobulin and lysozyme, and protein as a whole.


Physical foundations of the probability of biogenesis. For bigenesis-a particular kind of systmogenesis-to occur, certain physical and informative requirements were indispensable, especially: (1) the selforganization of new kind of negative feed-backs supported by the trans-substantial channels of information. These were certainly at first organized only on the submolecular level, each of them consisting of many charge-transfer connections. The accomplishment of requirement (1) depends on (2) and (3): (2) the organization of a sufficiently complex structure inside the agglomerated system. We should mention here the desagglomerated inorganic systems according to the archaic models: 'A' (Atoms) and P (astro-Planetary systems). In these prebiotic models the selfregulation background consists of the kind of negative opposing forces). (3) the availability of molecules in which the structure complexity is sufficiently high to be able to contribute to the organization of the trans-substantial channels. Biogenesis of spontaneous trans-substantialization of information channels in feed-backs. The trans-substantial channels are spontaneously organized in the biotic model, but they are also present in many technical electronic models of systems constructed by man. Therefore, it is no wonder that biogenesis probably occurred at the 10--6 m size level (compare the diameter of the microspheres of Fox and the concept of Ponnamperuma who mentions the size of the contemporary Micrococcus). Such a system position - inside the biotic unicellular sub-band (extended actually from 10--6 to 10--1 m) is faviourable for the organization of the high complexity of the structurogenic processes trajectories. It is at the nearest possible level to this region on the dimensional scale where a maximal plurality of the different joining forces exists...


Soil and water and its relationship to the origin of life. Soils of the terrestrial planets form at the boundaries between lithosphere, atmosphere and hydrosphere. Biogenesis occurred in these zones; thus, it is axiomatic that some, perhaps many, stages of biogensis occurred in intimate association with the mineral constituents of soils. Because of a high surface to mass ration and, consequently, a high surface reactivity, the layer lattice clay minerals are the most important of these. According to the geological record, clay minerals appeared very early on the primordial Earth. Recent investigations have confirmed their presence in carbonaceous meteorites and have indicated their occurrence on Mars. In this paper we collect pertinent physico-chemical data and summarize the organic reactions and interactions that are induced or catalyzed by clays. Many clay-organic reactions that do not occur readily at high water contents proceed rapidly at adsorbed water contents corresponding to surface coverages of one or two molecular layers. One or two monolayers of adsorbed water correspond to extremely dry or cold planetary environments. Some consequences of these facts vis á vis biogenesis on Mars are considered.


The begginning of photosynthesis.

The begginning of photosynthesis. There is no evolutionary continuity between photochemical abiosynthesis and bacterial photosynthesis. Rather, the photosynthetic bacteria are descendants of fermenters that did not use light. Photosynthesis and respiration, both using electron flow coupled with phosphorylation, have a common origin ('conversion hypothesis'), but photosynthesis came first. Anaerobic (nitrate or sulphate) respiration cannot have preceded photosynthesis as neither nitrate nor sulphate existed on the early earth. Sulphate was made first by photosynthetic sulphur bacteria. Nitrate arose even later, namely, in the aerobic biosphere produced by the blue-green algae, the first 'phytotrophs'. Photophosphorylation may have originated through the combination with membrane function of substrate level phosphorylation in reactionsand function of substrate level phosphorylation in reactions of photoproducts. Cyclic photophosphorylation arose while the biosphere was still reducing. It was supplemented later by processes for the light-based production of reducing power (NADH), ATP-powered electron flow, and subsequently light-powered electron flow with ATP production (noncyclic photophosphoryaltion). These later processes served the assimilation of CO2.


Evolution of oxygen by plants in relation to biosphere evolution. The process of water decomposition by plants is discussed in connection with biosphere evolution. This process consists of two parts: water oxidation and oxygen evolution. The origin of the water oxidation process took place after the synthesis of chlorine-type pigments, the structure of which corresponds to a more oxidized state than the bacteriochlorophyll type. The ability of plants to evolve oxygen is the result of a long evolution process. The capability of decomposing water in the lung wave length spectral region by algae and higher plants, which can be only seen under anaerobic conditions was discovered. This mechanism was suggested to be a reflection of a relict form of plant apparatus having operated under ancient, strictly anaerobic, conditions.


Definition of fluctuant hearing loss.

Definition of fluctuant hearing loss. In summary, fluctuant hearing loss is defined as a disorder of the inner ear characterized by fullness, roaring tinnitus, and fluctuations in hearing. It is believed to be caused by an inadequate absorption of endolymph from the endolymphatic sac, with or without one or more metabolic disorders, that interferes with the delicate balance between the production and absorption of endolymph and thus produces cochlear hydrops. This triad of fullness, roaring tinnitus, and fluctuant hearing loss resulting from cochlear hydrops is much more common than the quadrad of true turning vertigo, fullness, roaring tinnitus, and fluctuant hearing loss due to vestibular and cochlear hydrops known as Meniere's disease. Although patients with fluctuant hearing loss only may eventually develop vertigo as the chief complaint and then be said to have Meniere's disease, it is remarkable how many patients continue to suffer mainly from cochlear symptoms at all times. It would appear, because of the greater frequency of fluctuant hearing loss than in Meniere's disease, that the cochlear labyrinth is more susceptible to hydrops than the vestibular labyrinth. For the purposes of diagnosis and treatment it is very useful to separate patients into those with fluctuant hearing loss and those with Meniere's disease.


Normal anatomy of the inner ear.

Normal anatomy of the inner ear. The three parts of the inner ear have been reviewed: the membranous (endolymph containing) labyrinth surrounded by the osseous (perilymph containing) labyrinth, and the otic capsule of bone that encases the osseous labyrinth. This is a brief survey of the normal anatomy, but one must always remember that the hallmark of the temporal bone is variation.


A model for the coevolution of the genetic code and the process of protein synthesis: Review and assessment. The contemporary genetic code and the process of protein biosynthesis most assuredly evolved from a simpler code and process. We believe that there was obligatory coevolution of the two and that the earlier code and process must have involved a more direct linkage between the amino acids and the information macromolecule. We propose that an early form of translating existed in which amino acids were attached directly to the 'messenger' RNA along the backbone as 2'OH aminoacyl esters. These esters then condensed with each other on the RNA backbone yielding a peptide covalently attached to the RNA, without the use of tRNA's and ribosomes. THis presentation is concerned with experimental data which indicate that such a simple translation system is possible and must have involved the following steps: (1) formation of the aminoacyl adenylate anhydride, (2) transfer of the amino acid from the adenylate to immidazole, (3) transfer of the amino acid from imidazole to 2'OH groups along the backbone of RNAs, (4) condensation of the amino acids to yield peptides. Steps (1)-(3) have been confirmed in chemical systems. Our preliminary evidence indicates step (4) is also possible. The aminoacylation of polyribonucleotides and the subsequent formation of peptides is a dynamic and experimentally accessible system for studying genetic coding specfities and our present studies are now concentrated on step (4), looking for such specifities.


Amino acids in carbonaceous chondrites.

Amino acids in carbonaceous chondrites. For almost 20 years laboratory experiments have advanced the concepts of chemical evolution, particularly with regard to formation of the amino acids. What has been generally lacking is concrete natural evidence for this chemical evolution hypothesis. The recent development of sophisticated analytical techniques and availability of carbonaceous chondrites with a minimum of terrestrial contamination has resulted in the identification of amino acids which provide strong evidence for a natural extraterrestrial chemical synthesis. Since the initial find in the Murchison meteorite (a type II carbonaceous chondrite) of both protein and nonprotein amino acids with nearly equal abundances of D and L isomers, further studies have been carried out. These studies have revealed the presence of at least 35 amino acids; the population consists of a wide variety of linear, cyclic and polyfunctional amino acids which shows a trend of decreasing concentration with increasing carbon number. Investigations of the Murray meteorite (a type II carbonaceous chondrite) has produced similar results, but studies of the Orgueil meteorite (a type I carbonaceous chondrite) show only a limited suite of amino acids, some of which appear to be indigenous while others appear to be terrestrial contaminanats. A sample of the Murchison meteorite was extracted with D2O and in addition of 'free' amino acids, showing no deuterium incorporation, some amino acids showed the presence of deuterium suggesting either a 'precursor(s)' or hydrogen-deuterium exchange which require(s) formation of carbon-hydrogen bonds.


Electrophysiology of the cochlea.

Electrophysiology of the cochlea. With careful techniques it is possible to demonstrate three electric potential regions of the inner ear: an intracellular negative potential, a high positive potential in the endolymph that appears bounded at the scala media side of the tectorial membrane rather than at the reticular lamina, and the extracellular spaces, which contain a fluid at near zero potential. The tectorial membrane is also found to be at zero potential. Further research may yet uncover more details of the resting potential distribution as we become expert at placing microelectrodes and learn better ways of correlating potential with position. Surely the study of these resting potentials would contribute to our understanding of the mechanisms of fluctuant hearing loss because these first order potentials are intimately related to the state of health of the inner ear.


Microbial contributions to the evolution of the 'steady state' carbon dioxide system. Various processes for the production of carbon dioxide by microorganisms are presented. It is postulated that a 'microniche' developed in a reducing environment; a symbiotic relationship between alga-like organisms and bacterium-like organisms in the 'microniche' governed the production of carbon dioxide resulting in the establishment of the steady state carbon dioxide system in the sea.


Remarks on the chemical conditions on the surface of the primitive earth and the probability of the evolution of life. The inner planets were formed from smaller objects that had no gases associated with them. These objects contained relatively small amounts of water and carbon in a form similar to that found in carbonaceous chondrites. The first forms of life must have originated during the time when the water reacted with the carbon (and also with nitrides, phosphides, etc.), while the hydrogen formed by this reaction was continuously lost from the gravitational field of the Earth. About 10-44 atoms of carbon reacted with water during less than 10-17 s. The crucial question is whether some form of life will always develop under these conditions, or whether the origin of life is an improbable, perhaps an immensely improbable event. At present it is still impossible to answer this question.


Ambiguity in the interpretation of abiotic syntheses. The main conclusion from abiotic syntheses is that modern organisms prefer molecular units that are easy to make. This could be the result of selection pressures during very early evolution rather than a reflection of the large scale molecular environment within which life first arose. As previously discussed (Cairns-Smith, 1971) there seems to be no good reason to limit our thinking on initial hereditary systems to those with chemical similarity to modern forms.


Formation of prebiochemical compounds in models of the primitive earth's atmosphere. II: CH4 - H2S atmospheres. In order to understand the role of sulfur in the primitive atmosphere, we have studied the action of a silent discharge on mixtures of CH4 and H2S at low pressure. The nature of the products formed in the gaseous phase, and the influence of several parameters, especially the H2S percentage, on the yield of the products are reported. The analysis of the products is carried out by gas liquid chromatography and infrared spectrometry. The formation of sulfur-containing compounds, such as thiols and sulfides, is reported. CS2 is formed in high yield (a few percent) in mixtures containing 40-50% of H2S, while the maximum concentration of thiols (i.e., CH3SH and C2H5SH) is reached with lower percentages of H2S. The formation of hydrocarbons decreases rapidly with increasing proportions of H2S. These results show the important inhibitor effect of H2S on the formation of hydrocarbons and the possibility of occurrence of many sulfur compounds in prebiological evolution.


Organic synthesis by quench reactions.

Organic synthesis by quench reactions. The effects of chemical quench reactions on the formation of organic compounds at a water surface under simulated primordial earth conditions were investigated for the study of chemical evolution. A mixture of gaseous methane and ammonia over a water surface was exposed to an arc discharge between an electrode and the water surface. This discharge served as a source of dissociated, ionized and excited atomic and molecular species. Various organic molecules were formed in the gaseous, aqueous, and solid states by a subsequent quenching of these reactive species on the water surface. The effects of these water-surface quench reactions were assessed by comparing the amounts of synthesized molecules to the amounts which formed during the discharge of an arc above the water level. The results showed that: (1) the water-surface quench reaction permitted faster rates of formation of an insoluble solid and (2) the quench discharge yielded twice as much amino acids and 17 times more insoluble solids by weight than the other discharge. The highest yield of amino acids with the quench reaction was 9 x 10-7 molecules per erg of input energy. These observations indicate that quench reactions on the oceans, rain, and clouds that would have followed excitation by lightning and shock waves may have played an important role in the prebiotic milieu. Furthermore, the possibility exists that quench reactions can be exploited for the synthesis of organic compounds on a larger scale from simple starting materials.


Diabetes mellitus in fluctuant hearing loss. 1. In 161 consecutive cases of fluctuant hearing loss and 13 control cases of other causes of deafness, patients were examined for their ability to metabolize a 100 gm. oral dose of glucose. 2. The plasma glucose level in response to the oral dose of glucose was measured at hourly intervals for three hours. 3. Insulin and proinsulin levels were measured in 46 cases of fluctuant hearing loss and in 13 control cases. 4. None of the control group showed borderline or diabetic tolerance curves. 5. Fourteen per cent of the patients with fluctuant hearing loss had borderline glucose intolerance curves and 19 per cent showed diabetic glucose tolerance curves. 6. In patients whose insulin and proinsulin levels were determined, the insulin response to an oral glucose load was typical of adult onset diabetes, i.e., delayed hyperinsulinemia with concomitant hyperglycemia. The hyperinsulinemia was not associated with hyperproinsulinemia. 7. We conclude that in patients with fluctuant hearing loss there is a significantly higher incidence of borderline or diabetic glucose tolerance than in the "control deafness" or "normal population" group.


Sudden hearing loss due to diving and its prevention with heparin. Vascular embolic and thrombotic problems postulated to be the cause of inner ear sudden deafness have been reported with decompression sickness also. Decompression sickness has been found to lead to cochlear potential loss in the guinea pig, and these losses are minimized by the prophylactic administration of heparin. Preliminary results show that inner ear hemorrhage may be associated with diving deafness, but plasma protein leakage into the perilymph of the ear may precede the hemorrhage. Inner ear hemorrhage in diving deafness seems to be restricted to the microcirculation. Until we gain a better understanding of the pathophysiology of diving induced deafness, it would be premature to consider agents such as heparin for the treatment of the problem in man.


Diagnosis and treatment of fluctuant hearing loss. Fluctuant hearing loss, a very real and common cause of sensorineural hearing loss, is probably due to cochlear hydrops resulting from an anatomically inadequate endolymphatic sac, poor circulation, and one or more metabolic disorders. In the early stages at least, it often responds to treatment.


Audiometry in fluctuant hearing loss.

Audiometry in fluctuant hearing loss. Fluctuant hearing loss is a very complex matter, which involves not only neurological and physiological concepts but considerable acoustic factors as well. Fluctuant hearing loss is perhaps more visible with the use of pure tone audiometry because of the nature of its effect, the variation in the compliance properties of cochlear tissues. This visibility is due to impedance factors that bear on the inner ear as well as on the middle and external ear regions. It is suggested that changes in compliance of the cochlear tissues play a significant role in the existence of reduced sensitivity to low frequency pure tones. This indicates that sensorineural conditions with loss of hearing in the low frequency region may be a composite of conditions: sensory cell damage, which is only seen by high frequency response, and disturbance in the cochlear tissues, increasing their stiffness and resulting in loss of sensitivity for low frequency tones. When hearing damage is found in the inner ear exclusively because of permanent destruction of sensory cells, this theoretical model predicts that the fluctuating nature of certain types of hearing impairment ceases.


Control of the microcirculation of the inner ear. In general, many similarities are seen between cerebral blood flow and cochlear blood flow in response to vasodilating drugs. Cochlear vessels appear to be weakly controlled by the adrenergic nervous system. Cholinergic agents dilate cochlear vessels, although the vasodilation in the cochlea does not necessarily cause an increase in cochlear blood flow because of the associated hypotension. The effect on the systemic circulation is too profound to make these agents clinically useful. Papaverine, dipyridamole, amyl nitrite, and the plasma kinins produce transient increases in cochlear blood flow. Ten per cent carbon dioxide and 90 per cent oxygen product progressive vasodilation as long as the mixture is inhaled. Hydralazine produces too profound an effect on systemic blood pressure. Histamine and betahistine increase cochlear blood flow but only in doses that produce bronchiospasm in the guinea pig. Nicotinic acid and nicotinyl tartrate have no effect on cochlear blood flow. If one considers safety and efficacy as well as patient tolerance, papaverine appears to be the drug of choice for increasing cochlear blood flow clinically. Histamine and betahistine appear to be acceptable alternatives. Betahistine is no longer available for clinical use because of the failure to demonstrate clinical efficacy of therapy.


The role of allergy in fluctuating hearing loss. A method for the selection of patients with fluctuating hearing loss and Meniere's disease for allergic evaluation is presented. An approach to the diagnosis and treatment of these problems is reviewed. Seventy-two patients with Meniere's disease who met the criteria of the American Academy Subcommittee on Equilibrium and Its Measurements were evaluated. Thirty-two per cent of the 62 patients receiving allergy therapy or allergy and metabolic therapy responded to treatment. Half required a combination of metabolic and allergy management, whereas the other half responded to allergy therapy alone.


Recovery of a new herpesvirus from the ground squirrel (Citellus citellus). A new herpesvirus recovered from the kidneys of mature ground squirrels (Citellus citellus) produced an effect in tissue culture cells resembling that of herpesviruses, including the formation of multinucleated syncytia and type A intranuclear inclusions. The isolate caused latent infection in the natural host, but it proved fatal for intracerebrally inoculated suckling mice and it produced pocks on the chorioallantoic membrane of embryonated eggs. Electron-microscopic examination of infected cells revealed intranuclear virus particles exhibiting a size and ultrastructure characteristic of herpesviruses. The isolate was ether-resistant and a DNA nucleic acid type was inferred from observations on inhibition by fluorinated pyrimidine. This ground squirrel herpesvirus was found to be antigenically distinct from Herpesvirus hominis and from ground squirrel cytomegalovirus, with no detectable cross-reactivity.


The source of ascitic fluid in experimental cirrhosis in the rat. In order to disclose the source of ascitic fluid in liver cirrhosis, normal and cirrhotic rats were injected with fluorescein into the paracecal vein. The green fluorescence was then evaluated on the surface of the liver, the intestine and the peritoneum. Among healthy rats and in those with anascitic cirrhosis a very slight fluorescence was detected on the liver capsule whereas among rats with ascitic cirrhosis a distinct fluorescence was shown on the liver surface, the small intestine and the peritoneum. Therefore, the peritoneum is a source of ascitic fluid in cirrhosis of the rat.


Rhabdomyosarcoma in childhood.

Rhabdomyosarcoma in childhood. Fifty-four rhabdomyosarcomas in children affected mainly the pelvis and scrotum, 22 cases, head and neck, 19, and limbs and limb girdles, 11. Rhabdomyosarcomas of the female genital tract occurred only in children under 2 years, and those in the lower eyelid presented in the first year of life. A leiomyosarcoma-like appearance, and an undifferentiated small cell sarcoma sometimes mimicking Ewing's tumour, were patterns giving rise to diagnostic difficulty. Many fine gradations from undifferentiated embryonal to almost purely differentiated "pleomorphic" examples, made microscopic classification arbitrary. However, the histological pattern had no bearing on prognosis in children in this series. Of the 46 cases adequately followed, 43 are dead. Two of the 3 long-term survivors had paratesticular tumours.


The limitations of statistical correlations in pathology. Many hypotheses as to the causes of disease, for example some of those for coronary heart disease, depend on statistical correlations. It is well known that correlations do not prove a cause-and-effect relationship, yet it is often tempting to ignore this axiom.


Effect of sodium chloride and sucrose in agar media on growth of staphylococci at high temperatures: a brief communication. Sodium chloride and sucrose were shown to elevate the maximum temperature at which both coagulase positive and coagulase negative staphylococci would grow on the surface of nutrient agar. All of 200 isolates tested showed this effect.


Banded structures in cauda equina.

Banded structures in cauda equina. Banded structures identified in a cauda equina biopsy from a patient with compression are identical to those seen in schwannomas and several other conditions and identified as fibrous long-spacing collagen. They are present in relation to the basement membrane with a periodicity of about 1200 A. It was not possible to identify their substructure further. It is postulated that the initiating factor in their formation in this instance is compression of the spinal nerves.


The ovarian dysgenesis of trisomy 18.

The ovarian dysgenesis of trisomy 18. Ovarian abnormalities have been reported as a rare feature of the trisomy 18 syndrome. Gross and histological examination of autopsy material from 13 female infants with this syndrome revealed that ovarian dysgenesis, in varying degrees of severity, is more common than is indicated by the literature. The characteristic changes are reduction in germ cells due to necrobiosis, and the presence of mesothelial clefts and abnormal masses of stromal cells.


A modified assay of total faecal bile acid excretion for clinical studies. Faecal bile acid excretion was estimated in a clinical laboratory using gas liquid chromatography. The original method of Grundy et al was simplified so that quantitative thin layer chromatography was not required. Rigid dietary control or inpatient facilities were unnecessary for clinical studies. Control patients studied under these conditions had a daily faecal bile acid excretion of 0.37 +/- 0.13 g/day. Patients with ileal resections varied markedly with bile acid excretions ranging from 0.25--6.32 g/day (mean 2.36 +/- 1.11).


Spontaneous regression of melanoma.

Spontaneous regression of melanoma. Primary cutaneous melanoma has a tendency to disappear spontaneously. Histologically the active phase is characterized by a dense infiltrate of lymphocytes similar to that seen in spontaneously disappearing naevi. The regression process may continue until the tumour has been completely destroyed, or it may cease when only a part of the tumour has been destroyed. The lymphocytes disappear when the process halts leaving vascular scar tissue with a variable number of pigment-containing phagocytes. As a result of this a certain number of distinctive clinical patterns can be recognized: (1) An inflammatory nodule with or without pigmentation; (2) scarring in the tumour; (3) several foci of melanoma simulating multicentricity; (4) pigmented lesion with a depigmented halo; (5) pigmented scar with surviving melanoma cells; (6) pigmented scar without surviving tumour cells; and (7) metastatic melanoma with no demonstrable cutaneous primary. Only melanomas with a component of superficial spreading type have been found undergoing spontaneous regression.


Phenylalanine hydroxylase activity in liver biopsies from hyperphenylalaninemia heterozygotes: deviation from proportionality with gene dosage. Liver biopsy samples from the patients with hyperphenylalaninemia have an average of 5 percent of the normal hydroxylase activity. The parents of the patients have between 7.3 percent (excluding the value for one parent) and 10 percent of the normal hepatic hydroxylase activity. An explanation for these findings involves negative interallelic complementation, which involves protein-protein interaction between subunits in a multimeric enzyme. In support of this model is the evidence that rat liver phenylalanine hydroxylase is a multimeric protein composed of two electrophoretically distinguishable subunits.


Catecholamine-binding brain protein in mice exposed to perinatal malnutrition and neonatal infection. The formation and specific activity of a catecholamine-binding brain protein were studied in mice exposed to perinatal malnutrition and neonatal infection. In the malnourished group, the total norepinephrine (NE)-binding protein was less than in the control group (malnourished 7.1-10.0 mg; control 13.0-14.0 mg), but the dopamine (DM)-binding protein was not significantly affected. In the infected group, the quantity of NE-binding protein was also decreased (infected 6.4-8.0 mg), but the DM-binding protein was higher than in the control group. The specific and total binding activity of [3H]NE to brain protein was greatly reduced in the infected group (infected 22.6 pmol/mg protein; control 88.4 pmol/mg protein), and decreased also in the guanidine-HCl eluate of the malnourished group (56.5 pmol/mg protein). The binding activity of [14C]DM was decreased markedly in the infected group (infected 131 pmol/mg protein; control 330 pmol/mg protein), but its specific binding activity was not as severely affected in the malnourished as in the infected group. The molecular weights of the catecholamine-binding protein were 75,000 in the control, 70,000 in the malnourished and 65,000 in the infected groups. There were no marked differences between the malnourished and control groups with regard to the amino acid composition of the NE-binding protein. The DM-binding protein in these animals had decreased amino acid content. The infected group exhibited remarkable changes in NE- and DM-binding brain protein.


The choline incorporation pathway: primary mechanism for de novo lecithin synthesis in fetal primate lung. The two pathways of de novo lecithin synthesis, choline incorporation (I) and phosphatidylethanolamine methylation (II), were examined in lung slices from rhesus monkey fetuses throughout the last half of gestation. Incorporation rates of pathway-specific radioactive precursors were used as a measure of lecithin production. At all stages of development studied, pathway I incorporated 10-50 times more precursor ([14C]choline) into lecithin than did pathway II ([14C]methionine or [14C]ethanolamine). In addition, although methylation activity did not change significantly during gestation, choline incorporation showed three distinct phases: (1) a stable, relatively low rate in early gestation, (2) an abrupt, twofold increase at approximately 90 percent of term, and (3) a return to lower activity levels in late gestation. This correlates with reports that lung lecithin concentration in fetal primates increases significantly in the last 10 percent of gestation. The lecithin to spingomyelin (L/S) ratios measured in amniotic fluid samples obtained at abdominal delivery were compared with pathway activities in lung slices from the same fetuses. Significant correlation was found between the amniotic fluid L/S ratio and pathway I activity (r = 0.77, P less than 0.001); in contrast, pathway II activity showed no relationship to the amniotic fluid L/S ratio. Thus, the L/S ratio appears to be a reflection of lung lecithin synthesis through the choline pathway. The conclusion that the choline pathway is the primary route of de novo lecithin synthesis in the nonhuman fetal primate lung is supported by three lines of evidence, (1) the predominance of choline incorporation into lecithin, (2) the late gestational rise in conversion of choline to lecithin, and (3) the correlation between pathway I activity and both lung lecithin concentration and amniotic fluid L/S ratio.


Clinical features of renovascular hypertension in infancy: report of a 9-month-old infant. Certain common but seldom recognized clinical features of renovascular hypertension peculiar to infancy are emphasized in this communication from the observations made in a 9-month-old infant. Failure to thrive, extreme irritability, hypotonia, anorexia, vomiting, diarrhea, respiratory distress, and congestive heart failure are common clinical findings. Unless the physician is aware of this symptomatology or blood pressure is routinely obtained in all infants, the condition is likely to be missed. Renovascular hypertension is malignant and carries a high mortality but if diagnosed early may be cured by surgical intervention.


Inguinal hernia: a common problem of premature infants weighing 1,000 grams or less at birth. Thirty percent of 37 consecutive surviving premature infants weighing 1,000 gm or less at birth were noted to develop inguinal hernias. Incarceration occurred in two infants. One infant suffered a cardiac arrest during repair of the hernia. In view of the increased survival now being reported in these tiny prematures, it is important that physicians recognize the high incidence and potential hazards of this congenital anomaly in surviving premature infants weighing 1,000 gm or less at birth.


Occult recurrence of nasopharyngeal rhabdomyosarcoma manifesting as isolated increased intracranial pressure. In this paper we report a child who had extensive neoplastic infiltration of the meninges which defied clinical detection. We believe that any patient with a past or present history of tumor who presents with increased intracranial pressure should be presumed to have intracranial neoplastic involvement, even in the face of negative diagnostic studies. As in this case, other causes of increased intracranial pressure should be systematically excluded.