Cervical spine injury in patients with ankylosing spondylitis.

Fractures of the cervical spine associated with ankylosing spondylitis are rare. Relatively minor injury can cause a fracture of the vertebral body or through the ossified intervertebral space, because of the loss of normal flexibility, mobility, and elasticity in the rigid spine. Sixty-six per cent of the fracture subluxations of the ankylosed spine are associated with injury to the spinal cord, and the mortality rate is 40%. Because of the complete nature of fracture and instability, there is a high risk of neurologic deterioration. Immobilization of the cervical spine in a Halo cast appears to be the treatment of choice. If skull traction is applied the cervical spine should be immobilized in the neutral position, and overzealous traction exceeding 10 pounds should be avoided. Callus formation and fracture healing following immobilization is rapid.  Four new cases are described and 44 previously reported cases in the literature have been reviewed.


Nonoperative treatment of splenic injury--report of a case.

A case of subcapsular hematoma of the spleen in a 19-year-old soldier is presented, in which nonoperative treatment was chosen. More than 3 years postinjury the patient appears in excellent condition, with no palpable left upper abdominal mass palpable. The literature on nonoperative treatment of such injuries is discussed. The present authors remain in favor of operative treatment of proven cases of splenic injury.


Chemotherapy in experimental toxoplasmosis: comparison of the efficacy of trimethoprim-sulfur and pyrimethamine-sulfur combinations.

Mice infected by intraperitoneal inoculation of the RH strain of Toxoplasma gondii were treated with various drugs. Trimethoprim was found to have no effect. Sulphamethoxazole, sulphadiazine and pyrimethamine had significant therapeutic effects on the course of murine toxoplasmosis. The therapeutic efficacy of sulphamethoxazole was enhanced by the addition of trimethoprim. A pyrimethamine-sulphadiazine combination was found to be superior to a trimethoprim-sulphamethoxazole combination in the treatment of experimental murine toxoplasmosis.


Trimethoprim-sulphamethoxazole in the treatment of enteric fever.

Twenty-three patients with typhoid fever diagnosed by blood culture were treated with co-trimoxazole (trimethoprim/sulphamethoxazole, 1 :5) at a dosage of 10 mg trimethoprim/kg/day in two divided daily doses for 10 days. Twenty-two patients responded, the mean period to defervescence being three days and to relief of toxaemia being 1-7 days. Another nineteen patients with similarly proven typhoid were treated with chloramphenicol (100 mg/kg/day) in four divided daily doses for 10 days. Eighteen patients responded, defervescence occurring in an average of 4-1 days and relief of toxaemia in a mean of 2-6 days. None of the patients included in the study developed complications, relapses or became a convalescent carrier during the period of observation.


The quantitative determination of griseofulvin by gas chromatography (ECD-GC).

Serum and organ griseofulvin levels in guinea pigs and serum levels in patients who received a prolonged oral administration of griseofulvin were determined gas-chromatographically. In guinea pigs liver showed the highest concentration of griseofulvin, followed by kidney and serum in the decreasing order. The skin levels were 0.16 approximately 1.51 mug/g with a dose of 30 mg/kg. In humans it was proved that griseofulvin did not cause any accumulation in the serum with a dosage of 500 mg/day.


Growth dependent changes of glycolipid compositions of mouse ascites tumor cells.

Total glycolipid compositions of mouse ascites tumor cells harvested at various growth stages with different growth rate were compared. MM2, MH134, Ehrlich and L1210 cells were used. Some growth dependent changes common among different cells strains were observed: (1) the amount of ganglyosides generally increased with decreasing growth rate of the cells; (2) an unidentified minor ganglyoside (X2) having a strong reverse corelation with the growth rate of the cells was found; and (3) the amount of CMH, GM3 and another unidentified ganglyoside (X1) had positive corelation with the growth rate.


Studies on rat complement. I. Immune adherence and immune hemolysis activities of rat serum.

The measurement of immune adherence reactivity of rat complement is possible at 20 degrees C but not at 37 degrees C. At 37 degrees C, EA rat C1423b site was destroyed by C3b inactivator present in rat serum. The optimal temperature for immune hemolysis reactivity of rat serum is either at 20 degrees C or 21 degrees C and dose response curve showed Von Krough equation with 1/n = 0.25 +/- 0.02. Al lower temperature, rat complement showed much more effective formation of C3 site to reacti with human erythrocyte in immune adherence as compared with guinea pig complement. The measurement of immune adherence reactivity of rat complement was not possible due to C3b inactivator at 37 degrees C but possible at 20 degrees C. It is possible due to lowering the reactivity of C3b inactivator and keeping the reactivity to form active C3b site in immune adherence reaction. Rat complement is more effective to make C3 site as compared with guinea pig complement. This explains the reason why EDTA rat serum has known to be most effective source of late acting complement for measurement of C1 and C2.


Toxicological approaches to the metabolites of Fusaria. X. Accelerating effect of zearalenone on RNA and protein syntheses in the uterus of ovariectomized mice.

In order to clarify the mode of action of zearalenone, a uterotrophic mycotoxin of Fusarium species, biochemical alteration of uterine tissue of ovariectomized mice were investigated. Administration of zearalenone to the mice induced an increase in contents of uterine RNA, protein and DNA. In vitro incubation of uterine tissue isolated from zearalenone-pretreated mice demonstrated a temporal elevation of RNA and protein syntheses. Accelerating effect of zearalenone on the cellular permeability to 14C-alpha-aminoisobutyric acid, 14C-(3-O-methyl)-glucose and 3H-uridine was also demonstrated, and this alteration of uterine permeability is presumed to be a primary effect of zearalenone.


Dissociation of lipid and protein from cell-DNA by direct alkaline sucrose gradient analysis.

Hela cells and normal human embryo cells were analyzed in alkaline sucrose gradients after labeling with 14C-thymidine and 3H-choline chloride or 3H-amino acid mixture. Radioactivities from both choline and amino acids were observed in accord with DNA peak when the labeled cells were analyzed after 1 or 2 hour lysis in the lysing solution at 25 degrees C; i.e., a sharp and high peak observed with HeLa cells and a peak with more reduced sedimentation rate observed with normal human embryo cells could be considered to indicate the association of DNA with lipid and protein components, probably the nuclear membrane. The peak which was obtained after 4 hour lysis at 25 degrees C or after 1 hour lysis at 37 degrees C was not associated with label from choline and amino acids and, thus, proved to have been released from lipid and protein fractions. When metaphase HeLa cells were collected after labeling with choline or amino acids and then analyzed, the radioactivity was demonstrated in the sharp and high peak after 1 or 2 hour lysis at 25 degrees C; that is, the lipid and protein portions might be somehow associated with the mammalian metaphase chromosomes.


Interaction in culture between mouse ascites mammary carcinoma (MM2) cells and lymphoid cells of isologous mice.

MM2 cells, ascitic tumor originated from spontaneous mammary carcinoma of C3H/He mouse, were mix-cultured with lymphoid cells of thymus or mesenteric lymph nodes from isologous animals of the same sex. The interaction in culture between these cells was examined by time-lapse cinemicrography. In single culture, thymocytes, mesenteric lymph node lymphocytes and MM2 cells were kept for 7 days with little change in cell population. Lymphocytes of both sources showed a marked decrease in cell number when cultured together with MM2 cells, being evidently phagocytosed by MM2 cells. Lymphocytes from MM2-bearing mice or mice sensitized with deoxycholate-extracted MM2 antigen were also all phagocytosed. MM2 cells exhibited no sign of damage or degeneration due to the phagocytosis. Thymocytes were not phagocytosed by histiocytes obtained from ascitic fluid 3 days after i.p. injection of 5% starch suspension. Phagocytosis of erythrocytes or lymphoid cells from spleen by MM2 cells was not detected.


Effects of Na+ and K+ on the resting membrane potential of the rabbit sinoatrial node cell.

To estimate the "resting potential" of the sinoatrial node cell, membrane potentials in quiescent states under various conditions were compared with the holding potential at which no net membrane current flowed during the voltage clamp. The membrane potential of the rabbit sinoatrial node cell was recorded using a conventional microelectrode method. The single sucrose gap method and the double microelectrode method were employed for the voltage clamp. The membrane potential immediately before the resumption of the spontaneous activity in normal Tyrode solution after a quiescence in high K+ concentration, in low Na+ concentration or in low temperature was approximately - 37 m V and was similar to that of the temporarily quiescent sinoatrial node cells after dissection. The holding potential at which no net membrane current flowed was - 38.4 m V, which coincided with the membrane potential during quiescence. The resting potential in quiescence increased by approximately 17 m V for a tenfold decrease in the extracellular Na+ concentration, and 22 m V for a tenfold increase in the K+ concentration. The relative membrane conductance decreased transiently on removing Na+ from the bathing medium. These findings suggest that a potential equivalent to the resting potential existss in the S-A node cell approximately 20 m V positive to the maximum diastolic potential, and this low value might be due to the high Na+ conductance of the cell membrane.


An electrophysiological study of the sacculo-ocular pathways in cats.

Microelectrode recordings of neuronal activities in the cat were made in the vestibular main nuclei and the y group cells in response to stimulation of the saccule and IIIrd (oculomotor) nuclei. A relatively new anaesthetic (Ketalar, Parke Davis Co.) that apparently did not suppress transmissions through the sacculo-oculomotor pathways was used. A social accessory arm to replace one side of the standard stereotaxic frame was designed to permit surgical access to the inner ear. Orthodromic focal potentials indicating monosynaptic activation were recorded in the region of the lateral and inferior vestibular nuclei in response to ipsilateral stimulation of saccule. Antidromic field potentials in response to IIIrd nuclear stimulation were also recorded. Similar results were obtained from the y group cells. Unit recordings demonstrated that neurones in the rostral part of the lateral vestibular nucleus received monosynaptic excitation from the saccule before projecting to the IIIrd nuclei. However, studies on the y group cells indicated the existence of a separate and distinct pathway in the sacculo-oculomotor reflex. This pathway involves at least three synapses before reaching the motoneurones.


Cyclical effects of triiodothyronine on blood-free fatty acid and glucose concentrations in warm-adapted and cold-adapted rats.

Effects of triiodothyronine (T3) (100 mug/100 g, sc) on blood-free fatty acid (FFA) and glucose concentrations were investigated in warm- and cold-adapted rats. Blood specimens were obtained from the tail locally anesthetized with lidocaine. In warm-adapted rats FFA rose 3 to 6 hr after administration of T3, but returned to the pre-injection level 12 hr later. Thereafter, blood FFA level showed a repeated cyclical rise and fall every 12 hr for up to 60 hr, while blood glucose level did not increase until 12 hr later and this level was maintained for up to 36 hr. After that time it also showed a repeated rise and fall every 12 hr for up to 60 hr. Both FFA and glucose levels returned to the initial values after 72 hr. Changes induced by T3 in blood levels of these metabolites were reciprocal. In cold-adapted rats the patterns of responses to T3 were essentially the same as those observed in warm-adapted ones, except that T3 provoked a simultaneous rise in blood glucose as well as FFA 6 hr after injection, although an extent of FFA increment was less than in warm-adapted rats. Reserpine pre-treatment caused a considerable reduction in the FFA mobilizing action of T3. The FFA and glucose mobilizing action of T3 was also observed at dosages of 25 and 6.25 mug/100 g, although to lesser extent. These results indicated for the first time the cyclical action of T3 on blood FFA and glucose concentrations, and a changed sensitivity to T3 in cold-adapted animals.


Effect of an increase in cardiac output on the in vivo C02 titration curve of mixed venous blood.

The slope of the in vivo CO2 titration curve of blood (pH-[HCO3-]p relationship, in vivo slope, unit: slyke) expresses the buffering capacity of blood for CO2 in vivo or the buffering capacity of extracellular fluid for CO2. It depends on the extent of contributions by chemical and physiological buffering processes for CO2 occurring during CO2 titration. Theoretically, the in vivo slope obtained for mixed venous blood is independent of cardiac output during CO2 titration. The present study was attempted to confirm this theoretical concept experimentally. Anesthetized dogs were allowed to breathe air and then 10% CO2-25% 02 in N2 for 60 min for the titration in vivo. During the CO2 breathing period the legs were exercised through direct electrical stimulation of the muscles; this also induced an increase in cardiac output 130% above the air breathing period. The in vivo slope (delta[HCO3-]p/delta/pH-]p/"pH) of the mixed venous blood at an apparent steady state in the CO2 breathing period was 16 slyke, which was 5 slyke higher than in other dogs breathing CO2 at rest with a 60% increase in cardiac output observed in our previous study. This finding was discussed in relation to a greater contribution of tissue fluid for buffering of CO2. The present study suggests that cardiac output is a significant determinant of the buffering capacity of extracellular fluid.


In vivo lipolytic effect of glucagon in warm-adapted and cold-adapted rats.

In vivo effect of glucagon on blood-free fatty acid (FFA) concentration was investigated in rats adapted to 25 degree C and to 5 degree C. Intraperitoneal injection of glucagon in 100 or 25 mug/100 g body weight doses was followed by a triphasic response in blood FFA concentration: an immediate and marked rise at 5 min, a secondary depression at 60 min and a final rise at 120 to 240 min after the injectionss. For the 12.5 and 6.25 mug/100 g body weight injections, an initial increment was significantly lowered and no elevation at 240 min was observed. Concomitant elevations of blood glucose concentration were shown 5 min after glucagon injection of 100, 25, 12.5, and 6.25 mug/100 g body weight doses and their extents were not significantly different each other between these doses. However, rise in blood glucose level at 60 min was not seen at the 12.5 and 6.25 mug/100 g body weight doses. Blood lactate concentrations did not show any significant variations by the injections of glucagon. In fasting rats, glucagon at the 100 mug/100 g body weight dose caused similar increase in blood FFA as that in fed ones. In fed cold-adapted rats at 5 degree C glucagon at the dose of 100 mug/100 g body weight brought about similar effects in elevation of blood FFA level and its time-course as those in fed rats adapted to 25 degree C. However, under fasting condition cold-adapted animals exhibited greater increment in blood FFA level at 5 min than those adapted to 25 degree C, while an elevation of blood FFA at 240 min was not observed in the former animals. These results indicate for the first time an in vivo lipolytic action of glucagon in rats and further suggest an enhanced sensitivity to lipolytic action of glucagon in cold adaptation.


Responses to field stimulation of the smooth muscle cell membrane of the guinea pig stomach.

The responses of smooth muscle cell membrane of the guinea-pig stomach to field stimulation were investigated. In response to a single field stimulation (0.1-0.2 msec), the longitudinal and circular muscles excised from the antrum of the stomach produced a small hyperpolarization which was blocked by treatment with tetrodotoxin. Repetitive stimulation at various frequencies lowered the amplitude of the slow potential change thus causing suppression of the spike generation and mechanical response. Phentolamine did not suppress the generation of the inhibitory junction potential produced by a single stimulation but did slightly suppress the hyperpolarization produced by repetitive stimulation. Tetrodotoxin suppressed the amplitude but not the frequency of the slow potential change, however repetitive field stimulation in the presence of tetrodotoxin did not reduce further the amplitude of the slow potential changes. After a single or repetitive field stimulation was applied, the muscle membrane produced a delayed excitation on the slow potential change. The delayed excitation, however, did not generate in the presence of tetrodotoxin or of atropine. Reversal level for the inhibitory junction potential was ranged between--80 and--85 mV. Externally applied noradrenaline and ATP suppressed the generation of slow potential changes. Noradrenaline slightly hyperpolarized the membrane and increased the ionic conductance of the membrane but ATP neither modified the membrane potential nor increased the ionic conductance of the membrane.


Electrophysiological and mechanical investigations on the dual action of prostaglandin E1 in the pregnant rat myometrium in vitro.

Effects of prostaglindin E1 (PGE1) on the myometrial activity of the pregnant rat were investigated by recording the contractile response and intracellular electrical activity. PGE1 (10-9--10-6 g/ml) caused a depression of the contractile activity in the fresh preparations of either longitudinal or circular muscle strip (within 2-5 hr after exposure to the artificial saline media). However neither membrane potential nor action potential was significantly affected by the treatment with the agents. By contrast, in the aged preparations (bathed in the saline media longer than 2-5 hr), an increase in the contractile response dose-dependently was caused. The generation of action potential was facilitated without depolarization of the membrane. The inhibitory response induced by PGE1 in the fresh preparation was converted to an excitatory response when treated with bretylium. The discussion covers the inhibitory effect of PGE1 which is mediated through intrauterine adrenergic system, and is perhaps due to the focal hyperpolarization block of the conduction of excitation. The excitatory effect is very likely caused by a direct action on myometrial cell membrane.


Intrarenal blood flow in carotid sinus nerve stimulation and hemorrhage in dogs.

The present study was undertaken to compare the role of the sympathetic nervous system, in hemorrhage, with that of hypotension in producing renal blood flow (RBF) redistribution. Ten mongrel dogs were prepared for the determination of RBF distrubition by injecting 85Kr dissolved in saline into the renal artery to obtain renal radioactivity curves. RBF distribution was determined a) at control, b) during a 15-min period of hypotension produced by electrical stimulation (10 v-60Hz) of the left carotid sinus nerve (nerve of Hering), c) 15 min after hemorrhage to a blood pressure equivalent to that of stimulation and d) during hemorrhage plus a 15-min period of stimulation. Hypotension caused by stimulation left component I blood flow unchanged (at approximately 492 ml/min/100 g) but resulted in an increase in component II flow from 93 +/- 8 to 155 +/- 20 ml/min/100 g. Hemorrhage caused a 60% reduction in component I blood flow rate, leaving component II unchanged. Partial reversal of hemorrhage effects on distrubiton of RBF was obtained by restimulation of the nerve of Hering. It appears that RBF distribution, as controlled by the carotid sinus, may involve primarily component I flow, with the redistribution between components I and II during hemorrhage possibly involving other mechanisms.


Influence of ethacrynic acid on intrarenal renin release mechanisms.

Ethacrynic acid infused i.v. in anesthetized dogs after inhibiting sympathetic mechanisms of renin release increased renal blood flow rate (RBF) by 54% and practically abolished autoregulation of RBF; renin release increased from 0.8 +/- 0.9 (mean +/- SEM) to 16.4 +/- 3.7 mug/min (P less than 0.05). Without infusion of ethacrynic acid; constriction of the renal artery to a pressure below the range of autoregulation reduced renovascular resistance markedly and renin release rose to 27.2 +/- 5.5 mug/min (P less than 0.05). During arterial constriction, ethacrynic acid had no additional effect on renovascular resistance or renin release averaging 28.4 +/- 6.7 mug/min. Infusion of ethacrynic acid and saline at control pressure increased sodium excretion to about one-half of the filtrate and reduced rein release which did not, however, return to control. Infusion of hypertonic saline during autoregulated vasodilatation induced by arterial constriction had a similar effect, but again renin release continued to exceed control. We propose that ethacrynic acid increases renin release through a hemodynamic mechanism triggered by afferent arteriolar dilation and inhibits renin release by greatly increasing the delivery of sodium to the distal convoluted tubules.


Renal function before and after unilateral nephrectomy in renal donors.

Measurements of glomerular filtration rate (GFR), effective renal plasma flow (ERPF), tubular maximum reabsorption of glucose (Tmglucose) and secretion of para-aminohippurate (Tmpah), clearance of inorganic phosphate (Cphosphate) and uric acid (Curic acid), urine diluting capacity (CH2O) and urinary net acid excretion (UH + V) were made before and 10 to 14 days after unilateral nephrectomy in seven healthy renal donors. Comparisons were made between the functions of the remaining kidney and 50% of pre-uninephrectomy values. Mean post-uninephrectomy GFR increased by 36%, and mean ERPF, 55%. Tmglucose, Tmpah, Cphosphate, uric acid, CH2O, UH + V increased significantly, after uninephrectomy. The increase in Tmpah, Tmglucose and CH2O is proportional to the rise in GFR while the increase in Cphosphate, Curic acid and UH + V is proportionally greater than the increase in GFR. The changes in post-uninephrectomy renal handling of phosphate are not due to an increase in parathyroid hormone secretion.


Urinary lactic dehydrogenase isoenzyme 5 in the differential diagnosis of kidney and bladder infections.

Urinary lactic dehydrogenase (U-LDH) isoenzyme assays were performed on ch2) as well as normal controls (N = 24). Docuemntation of bladder and kidney infection was accomplished by means of the bladder washout test, culture of ureteric urine (in patients with urinary diversion), kidney function studies including the maximal urine concentration test, clinical symptomatology and radiologic appearance of the urinary tract. Total U-LDH in normal children (10.8 +/- 1 mU/ml) was lower than in patients with bladder (27.0 +/- 3.9 mU/ml) or kidney (226 +/- 67.3 mU/ml) infections (P less than 0.005). In normal children isoenzymes 1 and 2 predominated (LDH-1 migrates fastest to anode -- fast zone pattern). In patients with bladder infections, the isoenzyme patterns varied but the concentration of isoenzyme 5 (3.1 +/- 0.8 mU/ml) was lower (P less than 0.005) than in patients with kidney infections (120 +/- 39 mU/ml). In the latter, isoenzymes 4 and 5 predominated (slow zone pattern). Since overlap between kidney and bladder infections regarding isoenzyme 5 concentrations (at 3 SD) occurred in only one individual (patient 37), a correct differential diagnosis using U-LDH-5 alone would have been possible in 94% of the children with pyelonephritis or 97% of the total patient population (kidney + bladder).


Measurement of residual glomerular filtration rate in the patient receiving repetitive hemodialysis.

The objective of the current study was to determine the best index of residual glomerular filtration rate (GFR) by comparing simultaneously measured clearances of inulin, 125I-iothalamate, endogenous creatinine, urea and 169ytterbium diethylenetriaminepentaacetic acid (169YB-DTPA) in patients receiving repetitive hemodialysis. In patients with GFR less than 5 ml/min but greater than 1 ml/min, 125I-iothalamate clearance showed the best correlation with inulin clearance. However, creatinine clearance correlated better with inulin clearance than urea clearance and as well as urea + creatinine/2. In the patients with measured GFR less than 1 ml/min, the correlation of 125I-iothalamate, creatinine, urea and urea + creatinine/two clearances with inulin clearance was satisfactory. Similarly, satisfactory correlations were obtained when the relationships were examined across the entire range of measured clearances less than 5 ml/min. A simple, practical method is descriged for the accurate serial measurement of residual GFR in patients receiving repetitive dialysis.


[Haemodynamic problems and eye (author's transl)].

Haemodynamic problems of ocular circulation are discussed with regard to blood pressure measurment in the eye, giving information about the blood circulation of the internal carotid artery. Investigations on the choroidal and retinal circulations show that, between these two tissue layers, the movement of extravascular fluid predominates from the choroidal capillaries to the retinal capillaries. A model of the pressure relationships in both of these vascular systems is constructed to substantiate this hypothesis.


[Technique and results of an operative treatment of keratoglobus (author's transl)].

The technique of a surgical treatment of keratoglobus in the form of a combined kerato-scleroplasty is described in detail, and the morphological and functional results on 5 eyes in four patients are discussed.


[Experiences with trepano-trabeculectomy (goniotrepanation) (author's transl)].

The authors report on a modificaioon of goniotrepanation according to Fronimopoulos where only the trabecular network is trepaned and the sclera is closed twice (trepano-trabeculectomy). The experiences, based on 172 operations of this kind showed, that the quick restoration of the anterior chamber after the operation reduces the postoperative complications. However, like the goniotrepanating operation the effect of the regulation of the intraocular pressure is based on the formation of a small filtering bleb. The operation is especially suitable for the treatment of primary glaucoma of adults.


[Transtrabecular iridectomy - a new surgical technique in the treatment of chronic narrow-angle glaucoma (author's transl)].

A new surgical technique in the treatment of chronic narrow-angle glaucoma is described. After forming a scleral flap and opening of Schlemm's canal a probe is inserted into the canal. We dissect the sclera and the outer wall of Schlemm's canal by an oblique cut. The probe being retracted again, the trabecular meshwork is cut and a basal iridectomy is performed. Then the scleral cut and the trabecular window are closed tightly. Postoperative pressure behaviour and gonioscopy indicate, that the outflow of aqueous humour occurs via trabecular cleft and the collector channels in the operating field; obviously with this technique the intrascleral outflow channels can be saved to a great extend.


[Pigment glaucoma. Scanning-electronmicroscopic findings. (author's transl)].

In case of a patient suffering from pigment glaucoma trabeculectomy was performed on both eyes. In one trabecular section the outer wall of Schlemm's canal, and in the other the trabecular framework were investigated by scanning-electronmicroscopy. The intertrabecular spaces were largely blocked by pigment granula, which, in some places, were stored in the clump cells of the iris. Even the outer wall of Schlemm's canal was dotted with pigment granula. The scanning-electronmicroscopic findings revealed the pigmental drainage blocking of the aqueous humour and explained the acute pressure rise in the pigment glaucoma with wide iridocorneal angle by an acute obstruction of the already largely blocked intertrabecular spaces.


[Clinical findings in phakolytic glaucoma (author's transl)].

1300 enucleated globes were examined from 1966-1974: Among these 20 eyes (1.5%) revealed a "phacolytic glaucoma" histologically. The clinical diagnosis before enucleation were "secondary glaucoma" or "absolute glaucoma" (19) and once "uveitis dolorosa". "Phakolysis" was considered in only 3 eyes. 15 cases revealed surprisingly well preserved retinal structure - indicating probable good function. The only therapy possible consists of immediate cataract extraction - inspite of high intraocular pressure. Phacolytic glaucoma must be considered in the differential diagnosis of unilateral "acute glaucoma"; also in young patients with traumatic and complicated cataract.


[Artificial divergence in treatment of anomalous correspondence (author's transl)].

Artificial divergence causes a change of correspondence in about 60% of cases of alternating comitant convergent strabismus. This means a merely formal normalisation, since only one third of the cases can be cured to a level of +/-1degree of arc related to the true position of the eyes. These cases do not show any scotoma under campimetry on the phase difference haploscop (Aulhorn). An other third achieved a status with a tolerance of +/- 2 degrees and microscotomata. The last third did not show a normalisation, mostly due to a preexisting angle smaller than 5 degrees of arc. The number of full cures was limited, since the onset of squint was early in the majority of cases. One half of the 271 cases were treated by surgical overcorrection and following reoperation. The other half by small initial surgery, prismatic overcorrection followed by prismatic compensation and small second operation.


[Carotico-cavernosus fistula after subclavia-carotis interna bypass (author's transl)].

A case of occlusion of the right common carotid artery combined with stenosis of the left common carotid artery is reported. Immediately after surgery a carotico-cavernosus fistula was observed on the right side. The clinical picture and the therapeutical problems are discussed; 4 X-ray and 2 fundus photographs are presented.


[Haemoglobinanomalies in ophthalmological practice (author's transl)].

Several patients with different haemoglobinopathies are discussed that show various ocular changes as a result of these diseases. The ophthalmological findings range from a Sludge-phaenomenon in the conjunctiva to capillary thrombosis in the ciliary body with accommodoplegia and peripheral uveitis to arterial obliteration, arterio-venous anastomoses, neovascularisation of the retina as well as secondary retinal detachment. Possibilities of treatment of these changes and problems of prophylaxis are discussed.


[Focal hemorrhagic chorioiditis (author's transl)].

The clinical and fluorescenzangiographic followup of 111 patients revealed, that focal hemorrhagic chorioiditis is a chronic disease with poor prognosis for visual acuity. After a median follow-up period of more than two years, only half of all involved eyes showed inactive scarring of the lesions. In 13% both eyes were involved. Corticosteroids, antiphlogistics and vasoactive drugs had no significant influence on the course of the disease. The therapeutic results with photocoagulation were more favorable. In 15 of 25 photocoagulated eyes a fast and permanent regression of the choroidal proliferations could be achieved.


[Chiasma-syndrome in arachnoidosis optochiasmatica (author's transl)].

A survey of the present knowledge of the pathology, clinical corues and prognosis of arachnoidosis optochiasmatica is given. Furthermore a case is described where the imminent loss of sight could be prevented by close cooperation with the neurosurgeon and well-timed operation.


[Long-term observation of a case with chorioiditis striata (author's transl)].

Peripapillary choroidal and retinal atrophy with tongue like extensions to the periphery are typical features of striate chorioiditis. They appear bilateraly in middle-aged persons and are of progressive course. A report on examination findings is made in a case with 20-year-old history. An abiotrophical process in the choroidea is discussed as cause of this disease.


[Eye changes in familial juvenile nephronophthisis (author's transl)].

5 patients from three families with confirmed diagnoses of nephronophthisis and eye changes are described. All patients showed along with relatively slight decreased function changes in the pigment epithelium and the choroid. In three of these patients the ERG was pathologically reduced. Contrary to the known observations from the literature our patients showed no typical signs of congenital retinal Leber's amaurosis. The observed changes in the sclera reflect the gravity of the illness. With dialysis treatment the progress of the disease could in two patients be arrested for 4 years.


[A new bifocal lens with the effect of a prism and a magnifying-lens in the near segment (author's transl)].

It will be reported about a new bifocal lens, that can be supplied with an additional prism in the near segment for close-range wark with an increased magnification up to +8.0 dpt.


[Fundus changes in Zinsser-Engman-Cole syndrome (author's transl)].

A case of Zinsser-Engman-Cole syndrome (Dyskeratosis congenita) with severe fundus changes is reported.


[Tapeto-retinal degeneration combined with incomplete general albinism (author's transl)].

Report on a family, which presented the rare autosomal dominant transmitted, incomplete general albinism associated with autosomal recessive inherited, diffuse tapeto-retinal degeneration "sine pigmento". hypopigmentation of skin, eyebrows and hair, blue iris and fundus albinoticus with hypoplasia of the macula. In 3 cases additionally appeared: waxy pallor of optic disc, vascular narrowing, reflexless hypoplastic macula, pigmentless periphery, acquired blue-yellow blindness, concentric limitation of the visual field, reduced darkadaptation, abolished electroretinogram and myopic astigmatism.


[Malignant melanoma of the iris - 23 years after incomplete excision of the tumour (author's transl)].

A 54-year-old male was 1948 submitted to a sectorial iridectomy because of a histologically proved malignant melanoma of the iris. 1971 an absolute secondary glaucoma had developed, and the eyeball was excised. Though histologically tumour issue of the original type was found in the chamber angle and ciliary muscle as well as around scleral blood vessels and subconjunctivally any clinical manifestation of generalization never was observed since the iridectomy 23 years ago.


[Asthenopia in workers of the ship-building industry (author's transl)].

8,032 workers were ophthalmologically examined. In 10.7% there were asthenopic complaints. In 4.6% the symptoms were caused by environmental factors, in 6.13% by organic factors.


[Expert opinion on the enucleation of an eye blinded in an accident following renewed traumatogenic contusion (author's transl)].

An eye blinded in an accident in the early childhood had to be enucleated after a new traumatogenic contusion. In this case is no claim to a pension.


Nitrogen loss in normal and obese subjects during total fast.

Healthy volunteers of ideal weight (12 men and 12 women) were fasted for 6 days, and obese but otherwise healthy subjects (20 men, 28 women) for 6--28 days. In all groups studied a significant increase in urinary nitrogen loss from day 1 to day 3 of fasting was followed by a steady decrease. The early rise in urinary nitrogen excretion coincided with a rise in plasma glucagon  levels, suggesting a relation of the latter to increased gluconeogenesis from amino acids. At equal weight greater nitrogen losses were found in men than in women, in both normal and obese subjects. In spite of much higher weight and larger energy expenditure and nitrogen loss in obese subjects however was not higher than in normal ones. Mean daily nitrogen losses varied from 14.5 g (normal and obese men early in starvation) to 3.0 g (obese women after a 4-weeks fast). Calculating the amount of calories derived from body protien (urinary nitrogen X 6.25 X 4.1)and taking total energy expenditure from tabular metabolic values, the contribution of protein to total calorie output was found to vary from 15% (normal men 6 day fast) to 5(obese women, 4th week of fasting). The clinical significance of nitrogen loss during therapeutic fasting is discussed.


[Metabolism of angiotensin II during angiotensin infusion and following sodium depletion].

1. Angiotensin II (A II) and angiotensin (3--8)-hexapeptide (H) were measured by radioimmunoassay in arterial and venous plasma before and during infusion of angiotensin II-amide in five normotensive subjects, both in sodium-replete and sodium-depleted states. The separation of the oligopeptides was performed by thin layer chromatography. 2. Before sodium-depletion the mean ratio of arterial to venous A II was 1.14+/-0.11:1, corresponding to an A II-extraction of approximately 12% during a single forearm passage. Infusion of A II-amide increased extraction of A II. The mean ratio of arterial to venous A II increased to 1.68+/-0.3:1, corresponding to an extraction of approximately 39% when 8 ng-min-1-kg-1 were infused. 3. Sodium depletion increased arterial and venous concentrations of A II and H. During infusion of angiotensin II-amide the arterial and venous concentrations of A II and H increased approximately parallel to the concentrations before sodium depletion. The extraction of A II did not differ significantly in both states. 4. The augmented extraction extraction of A II observed during infusion of angiotensin II-amide suggest an overproportional increase of the metabolism of A II under the latter condition. Sodium depletion, however, does not appear to cause a percent change in A II metabolism.


[Different reaction of plasma renin activity after propranolol in essential and renal hypertension].

In 16 normal subjects, in 29 patients with essential hypertension and in 25 patients with renal hypertension plasma renin activity was measured together with pulse rate and blood pressure under resting conditions and 15 minutes after the intravenous administration of 5 mg d-1-propranolol subsequently. Basal plasma renin activity (PRA) was correlated significantly to resting pulse rate in normal subjects and in patients with benign essential hypertension but not in patients with renal hypertension from chronic parenchymatous renal disease. In the normal subjects and in the patients with essential hypertension the decrease of not stimulated "basal" PRA 15 minutes after the administration of 5 mg d-1- propranolol was closely ralated to the initial plasma renin activity. In contrast, in the patients with well established renal hypertension the decrease of PRA was generally less pronounced or absent. Whereas in normal subjects as well as in patients with essentail hypertension in the sympathetic nervous system appears to be the major determinant for basal renin release, other factors, possibly the renal baroreceptors, may determine basal renin release in renal hypertension. This difference could possibley provide the basis for a simple biochemical test to differentiate between essential and renal hypertension.


Changes of fractional renal clearance of magnesium after spironolactone administration in normal subjects.

Spironolactone, 200 mg/24 hours, was administered for 4 days to 18 clinically healthy subjects and 10 hospitalised patients with normal renal function. Changes of fractional renal clearance of magnesium before and after spironolactone administration were studied in the first group. Corresponding changes of the ratio of renal clearance of potassium to renal clearance of magnesium were studied in the second group. After spironolactone administration, fractional clearance of magnesium showed a statistically significant decrease in relation to its values before spironolactone administration, while the ratio clearance of potassium/clearance of magnesium showed no statistically significant change. The results suggest that spironolactone administration decreases the renal excretion of magnesium and potassium in an equivalent manner.


[On the analysis of the hepatic-venous 133xenon-clearance after the application of the gas by inhalation].

After the inhalation of 133xenon continuous registrations of portal 133xenon concentrations showed that the monoexponential terminal component of the hepatic-venous 133xenon-clearance might be due to the recirculation of the gas from the gut. Accordingly, in all the cases, with the application of the wellknown "extrapolation and peeling off" of this monoexponential terminal component from this part of the hepatic-venous 133xenon-clearance, not affected any more by arterial recirculation a monoexponential 133xenon-clearance could be separated. The time-constant of the latter was similar to that of the well-knwon specific hepatic 133xenon-clearance after the application of the gas by injection into the portal vein.


Spontaneous renal subcapsular hematoma renal angiography as a diagnostic aid.

Prior to the development of angiography, a definite diagnosis of spontaneous subcapsular renal hematomaa was not often made preoperatively. The classic triad of blood loss, pain, and mass on the affected side is seldom presented by the patient. The one constant finding on scout film is an enlarged renal shadow, presenting a problem in differential diagnosis. Chief among cause of subcapsular renal hemorrhage are trauma, tumor, infarct, arteritis, and bleeding diathises. Selective renal arteriography gives specific information about the renal vascular supply and the state of the renal parenchyma not available by other means. Diagnosis of subcapsular renal hematom is facilitated by this modality. A correct diagnosis of subcapsular renal hematoma may well spare an otherwise innocent kidney. A review of current literature was undertaken, and three documented cases of spontaneous subcapsular hematoma diagnosed prior to surgery and confirmed at surgery are presented.


Squamous cell carcinoma of the oral cavity--chronic oral ulcerative disease as a possible etiologic factor.

This report documents the association of carcinoma of the oral cavity with chronic oral ulcerative disease in two patients. This association has not previously been documented in the surgical literature. Both patients in this report had chronic oral ulcerative disease preceding their cancers; however, the common etiologic factors for oral cancer were not detected in either case. Oral lichen planus and pemphigus vulgaris should be considered as potentially premalignant lesions and should be treated accordingly.


Chordoma: an analysis of twenty cases treated over a twenty-year span.

Chordoma is a recurring malignancy which does not play by the rules. A five-year survival or even a survival of ten years or longer without evidence of tumor cannot assure the surgeon that the malignant growth has been laid to rest. Recurring local episodes as well as metastases may continue to yield to surgery, irradiation, and other forms of treatment for an astonishing length of time. Thus, situations that may be cause for despair in other malignancies are often a challenge for renewed vigorous treatment in chordoma.


Retinoblastoma: an epidemiological study (survey and review).

An epidemiological study of retinoblastoma patients from Buffalo, New York, and Rio de Janeiro, Brazil, was conducted at Roswell Park Memorial Institute in 1974. Several important differences were uncovered as a result of this study. Patients in Buffalo with bilateral retinoblastoma were diagnosed most often within the first year of life and those with unilateral retinoblastoma after about 24 months of age. This difference in diagnostic age between the two forms of retinoblastoma is not demonstrated by the patients from Rio de Janeiro. Most of the Rio de Janeiro patients are 24 months or older before either type of retinoblastoma is diagnosed. By this time the disease has usually extended beyond the eyeball, and orbital exenteration is deemed necessary. Because the patients in Rio de Janeiro are diagnosed at an older age, these patients have a shorter length of survival and higher mortality as compared to the patients in Buffalo. Additional differences that were derived from this study will require further research for verification.


Evidence of oncogenic cofactors in radiation-induced tumors in mice.

Five groups of 587 inbred female mice (WHC) were studied to determine the incidence of tumors as affected by irradiation of different areas. A dose of 400 rad of 60Co was given to all the groups. One group of 166 mice was total body irradiated, another group of 90 mice was irradiated in the upper-third portion of the body, another group of 93 mice was irradiated in the lower two-thirds of the body, and another group of 90 mice was half body irradiated on the right side. As control, a group of 148 nonirradiated mice was followed. The results showed a different incidence of cancer in mice, depending not only on the irradiated areas but also on the shielded ones. This suggested that other factors besides irradiation affect carcinogenesis.


Simultaneous determination of plasma and urinary carcinoembryonic antigen levels.

The results of simultaneous plasma and urinary CEA levels in 14 patients are described. The aim was to determine whether urinary CEA derived from plasma or arose independently in the urinary tract. The method of reductio ad absurdum is followed. It is assumed that CEA in the urine is derived from plasma, and CEA clearance values for each patient are calculated. These varied widely from zero to a theoretical infinity. On this basis and from previous experimental evidence, it is concluded that urine is independent of plasma CEA. The finding, however, in some individuals of "anti-CEA"-like factor(s) distorting urinary CEA determination makes for some reservations about the safety of the conclusion. It is, however, certain that with the presently available technology, present urinary and plasma CEA values cannot be correlated.


Megestrol acetate for treatment of advanced carcinoma of the prostate.

Thirteen men, ranging in age from 53 to 73 years and with previously untreated metastatic carcinoma of the prostate, received megestrol acetate (a synthetic progestin) in doses of 120 mg daily. A beneficial clinical response with a mean duration of 47 weeks was achieved in 12 patients (92%). When relapse developed in 8 patients, a secondary response was readily obtained by orchiectomy. The results suggest that a staged hormonal approach, using progestin therapy initially, may offer additional palliation in treating patients with metastatic prostatic carcinoma.


Prognostic factors in Hodgkin's disease.

The clinical records and treatment results of 163 patients with Hodgkin's disease, who were seen at Ellis Fischel State Cancer Hospital (EFSCH) between 1940 and 1971, were reviewed and analyzed. More than 200 clinical and histological variables were recorded for each case of Hodgkin's disease, including details of radiotherapy and chemotherapy. Statistical studies were carried out in order to evaluate the independent prognosis significance of each of these factors. All of the lesions were reclassified according to the Lukes proposal which was modified and recommended at the 1965 Rye classification (except for hepatomegaly which was included in Stage IV). This is a retrospective study, and the modern techniques of staging were rarely used in pretreatment studies (since 1965, only ten patients have had an abdominal exploration). The basic work-up consisted of a complete blood count, urinalysis, blood type, chest X ray, and EKG. Lymphangiogram and radioisotope liver scans were used on less than 10% of the patients. About 30% of the patients had gastrointestinal X rays and 70% had IVP. Bone marrow biopsies -- the majority of which were done by needle aspiration -- were obtained for approximatley 50% of the patients. Clinical stage, histological type, and presence of absence of systemic symptoms appeared to be themost significant prognostic factors. The classification of systemic symptoms according to the criteria of either the Rye or Ann Arbor conferences showed no particular difference in determining the survival rate. Among the systemic symptoms, fever appeared to be the most important for survival rate. Survival rates were higher in nonanemic and nonlymphocytopenic patients. Eosinophilia, blood group, and Rh factor had no prognostic significance. The relapse-free interval was an important indicator of long-term prognosis. The unfavorable influence of relapse in ultimate prognosis was clearly seen; however, the extent of the relapse site was shown to have no significant influence on survival.


Rhabdomyosarcoma of the extremities and trunk: analysis of 150 patients treated by surgical resection.

This report details the clinical experience of 150 patients with rhabdomyosarcomas treated by one group of surgeons. Of the 150 patients, 103 suffered from pleomorphic rhabdomyosarcomas, 40 patients had embryonal rhabdomyosarcomas, and 7 had alveolar cell type of rhabdomyosarcoma. The males suffered almost twice as much as the females from this form of cancer (96 males to 54 females). The fifth decade had the highest incidence of all rhabdomyosarcomas. The younger patients generally suffered from embryonal rhabdomyosarcomas and the older ones from pleomorphic rhabdomyosarcomas, although age was no barrier to the occurrence of embryonal rhabdomyosarcomas in some of the older patients and pleomorphic rhabdomyosarcomas in some of the younger patients. Caucasians were almost exclusively afflicted by this form of cancer (93% of this series). The lower extremity was the most frequent site of the lesion, occurring in 50.7% of the 150 cases. The upper extremity was the second most frequently involved site (28%), and the trunk was the least involved site (21.3%). Of the 150 patients studied, 40 were considered indeterminate. Thirteen patients are alive and free of cancer, but were treated less than 5 years ago; 12 patients reported for consultation only. There were 13 who were free of sarcomas at periods in excess of 2 years but were lost to follow-up. Two patients in this series died before the 5-year period, and autopsy revealed the death to be due to causes other than the rhabdomyosarcoma. Of the 110 determinate patients, 75 (68%) died as a result of the cancer. The 5-year survival rate equals 32%. The fact of the 30% 5-year survival after treatment for recurrences should help dismiss the pessimism which prevails once a recurrence is noted subsequent to major therapy. Age per se had no great effect on prognosis. The poorest results occurred in the 11-20 age range, with a 5-year survival of 15%. This value reflects on increased incidence of embryonal rhabdomyosarcomas which tend to be more malignant and metastasize earlier than do the pleomorphic type. The effect of location upon survival revealed that of 76 patients with involvement of the lower extremity, 34% survived 5 years or longer, and those with sarcomas of the trunk had the poorest survival (26%). The fact that the trunk, by virtue of its anatomy, limits the degree of surgery that can be perfomred, probably helps to explain this difference. The role of radiation therapy and chemotherapy awaits elucidation. Reports of combined surgery, radiation therapy, and chemotherapy are encouraging.


Rectocolic reconstruction via a modified Kraske approach.

In carefully selected patients, the sacrococcygeal approach (Kraske's operation) with rectal colostomy can save a patient from abdominoperineal resection without loss of continence. This procedure is also useful in the management of rectal strictures that occasionally occur after leaks from the anastomosis of a low anterior resection of the rectosigmoid colon. Three illustrative cases are presented and discussed.


Cancer of the gastric stump following operations for benign gastric or duodenal ulcers.

Twenty-seven patients who developed cancer of the stomach after undergoing gastric resection (GR), gastroenterostomy (GE), and vagotomy and pyloroplasty (VP) for benign gastric or duodenal ulcer are reported. The etiology and the pathogenesis of this type of cancer are discussed. Long-term exposure of the gastric mucosa to bile and duodenal and pancreatic secretion reflux seems to create a premalignant potential state. Symptoms and the diagnostic methods of radiologic series, cytology, and endoscopy are discussed. We suggest a curative operative approach and discuss the poor value of palliative procedures. We emphasize the necessity of determining the prognosis with exploratory laparotomy which establishes at the same time the certitude of the diagnosis.


Skin test with tumor extract in bronchogenic carcinoma: a preliminary study.

Tumor-specific immunity using delayed hypersensitivity skin testing with extract of undifferentiated carcinoma of the lung was evaluated in 25 consecutive patients with carcinoma of the lung. Eight out of 25 patients reacted well to intradermal injection of the tumor extract. All of the 8 patients were found to have limited disease, and their survival times were longer than those with poor reaction.


By-pass anastomosis of intrahepatic duct to the gallbladder.

Obstruction of the extrahepatic bile ducts by primary or metastatic carcinoma can sometimes be diffiult to relieve. Frequently there is an inadequate length of normal duct proximal to the obstruction to permit an anastomosis. A by-pass anastomosis between a dilated right hepatic biliary radicle and the gallbladder is a simple and satisfactory method of relieving the jaundice. This can be accomplished by using a T-tube as a stent; a vein graft over the T-tube limb in the liver seems to improve the result.


A human/mouse hybrid model for the study of human genetic factors influencing tumor cell growth.

Somatic cell hybridization (fusion) was carried out between cells of the murine lymphoma L-5178Y(r) and peripheral human lymphocytes. The L-5178Y(r) line is deficient in hypoxanthine-guanine phosphorybosyl transferase (HGPRT). Using a selective medium system, it was possible to isolate hybrid cell clones having the complete complement of murine chromosomes as well as the human X chromosome on which the gene for HGPRT is located. This model system may be used to study the effect of the human X chromosome on the phenotype of the murine lymphoma.


The accuracy of liver scanning in the detection of metastatic disease.

Isotopic scanning of the liver to detect hepatic metastases is a commonly used clinical tool in assessing the extent of malignant disease and the proper mode of therapy. Opinions vary widely as to the efficacy of this test. To determine the accuracy of our scanning technique the clinical and laboratory data on 429 patients who had hepatic scans (technetium sulfur colloid) between February 1971 and May 1973 was reviewed. Of these patients, 125 had a confirmatory procedure (needle biopsy - 15, abdominal exploration - 69, autopsy - 41) done within 6 weeks of their scan. Nineteen patients who had negative scans were proven to have hepatic metastases. Fourteen patients had positive scans which could not be substantiated by one or more of the above confirming examinations. Thus the frequency of error was 25%. Regarding other tests - alkaline phosphatase and bilirubin - no better correlation could be made with respect to the presence or absence of metastases. From the data available on this small group of patients the liver scan is sufficiently inaccurate to preclude relying upon it for the selection of therapy in cancer patients. When the presence of hepatic metastases changes the type of therapy a confirmatory laparotomy or biopsy should be considered.


Further studies on a transmissible entity in relation to the control of cancer in mice.

Tumor-bearing mice of the C3H/ST inbreds were used in this investigation. Of the 598 mice, 290 were controls, 248 received injections of 5-methyl cytidine dissolved in physiological salt solution, and 60 received injections of three nucleosides - adenosine, 6-methyl adenosine, and 5-methyl cytidine - also dissolved in physiological salt solution. The mice were divided into 6 groups based upon the number of generations of descent from a mouse injected with an alcohol-soluble liver extract. The criterion of tumor growth is the average increment of growth at the 20th observation period in the 7th week (3 per week). There is a cumulative inhibition of tumor growth, compared with controls, when 5-methyl cytidine is added to the effect of a transmissible entity which occurs in the lineal descendants of a tumor-bearing mouse injected with an alcohol-soluble liver extract and when the combination of three nucleosides in the same ratio of molar concentrations as in the liver extract is added to the effect of the transmissible entity.


Carcinoma of the esophagus.

Life tables were computed from the Tumor Registry at the Medical University of South Carolina on 486 patients with histologically proven squamous cell carcinoma of the esophagus. The 5-yr follow-up was available in only 394 patients, or 81% of the total sample. For purposes of comparison with published literature, the traditional crude 5-yr survival percentages in the life-table analyses figures are presented. The life-table calculation utilizes all follow-up information available, in that patients observed for less than 5 yr still may contribute to the estimate of the true 5-yr survival rate in contrast to the past when all patients lost to follow-up were presumed to have died. In this method, patients not observed for the full time of the study are assumed to have had the same risk of dying as patients followed to the end of the fifth year experienced in their fifth-year analyses. The group with the most favorable prognosis in this series was that receiving preoperative irradiation. This operation. They were given 4,500 rads of supervoltage X ray over a period of 3 weeks prior to operation. The differences in surgical or radiation techniques employed by various reporters make comparative data difficult, if not impossible, to evaluate. Supervoltage irradiation has proved itself in some hands equal to surgery. A randomized prospective study would seem appropriate to conclude the best means of managing epidermoid carcinoma of the esophagus.


A computerized tumor-registry system for persons who do not love computers.

A new simplified system for updating a cancer registry has been developed in the Biostatistics Department of Roswell Park Memorial Institute. It was designed to serve the needs of maintaining a registry for a cooperative cancer research group. The Data-Update Procedure at a Remote Terminal (DUPART) system has general value for registry applications.


Vagotomy--a prospective, randomized study.

This is a report of a prospective randomized study of 3 operations for duodenal ulcer; parietal-cell vagotomy alone (without drainage), selective vagotomy with antrectomy, and truncal vagotomy with antrectomy. All patients in the study have been followed for a minimum of 1 yr and despite the small number of patients (total 23 in this report), there has been a statistically significant return of gastric secretory activity to preoperative levels in the parietal cell vagotomy group, while both other groups maintained decreased acid secretion at the 1-yr period. To date there has been one recurrent ulcer and one other suspected ulcer in the parietal cell vagotomy group, while both other groups have no ulcer recurrence even though morbidity has been higher (bile reflux gastritis, and so forth). This preliminary evaluation suggests strongly that extreme caution be used in applying parietal-cell vagotomy alone as a definite operation for duodenal ulcer, but because of the small number of patients involved no conclusions can be drawn at this time.


Phase I studies of porfiromycin (NSC--56410) in solid tumors.

Porfiromycin was given to a group of patients with a variety of solid tumors. Of 114 patients admitted to the study, 103 yielded evaluable data. The following dosage schedules were used to determine the toxicity of porfiromycin when given in multiple doses by intravenous injection: 0.2 mg/kg x 5 days, 0.3 mg/kg x 5 days, 0.35 mg/kg x 5 days, 0.4 mg/kg x 5 days, 0.24 mg/kg x 10 days and 0.6 mg/kg weekly. Toxic effects noted were mainly leukopenia, thrombocytopenia, and, when injected paravenously, local tissue necrosis. Biological effects were noted at all dosage levels and were more severe at the higher dosages. The data suggest that profiromycin administered intravenously at a dose of 0.35 mg/kg daily for 5 days results in moderate hermatological toxicity and clinical evaluation in a Phase II study at this dosage level is indicated.


Experience in the surgical treatment of diseases of the thyroid gland.

Over a 7-yr period from January 1967 to January 1974, 141 patients underwent thyroid surgery for various pathology at the Bexar County Hospital - University of Texas Medical School at San Antonio. Of these, 113 patients underwent subtotal thyroidectomy for benign diseases, including 28 of thyrotoxic patients who underwent subtotal thyroidectomy as definitive treatment. In this group of patients special interest and emphasis was placed in the preoperative and intraoperative management of the difficult and complicated hyperthyroid patient. Preoperative treatment was accomplished by the utilization of multiple drug combinations - including antithyroid drugs, adrenergic blocking agents, and iodine - which resulted in significant decrease in preparation time for surgery. Furthermore, this short intensive preoperative management of complicated hyperthyroid patients allowed satisfactory correction of their problems with little or no morbidity which otherwise would have been extremely difficult if not impossible to resolve. At operation, 28 patients were diagnosed to have malignant disease; 23 underwent total thyroidectomy and the other 5 had subtotal thyroidectomy. In addition to total or subtotal thyroidectomy, 23 patients had either classical or modified radical neck dissection including 9 patients who had bilateral neck dissection. The various surgical techniques utilized, the rationale for rapid preoperative preparation of complicated hyperthyroid patients, morbidity, and long-term follow-up are discussed.


Long-term intermittent adjuvant chemotherapy for primary, resected lung cancer.

Adjuvant chemotherapy for lung cancer has previously been unsuccessful in improving the results of pulmonary resections. During a 12 year period, we tested long-term intermittent chemotherapy (LTIC) with mitomycin C and chromomycin A3 adjuvant to resections. LTIC was begun before the operations and the first course was completed postoperatively. Additional courses of 4 weeks each were scheduled at 3 month intervals during the first postoperative year and at 6 month intervals during the next 2 years. LTIC was defined as three or more full courses, and short-term chemotherapy (STC) was defined as a single course of adjuvant treatment. Resections for cancer in 425 patients over a 22 year period included 117 operations during a 10 year control period in which LTIC was not used and 308 during the LTIC test period. Results from adjuvant LTIC in 85 patients were compared with lesser adjuvant chemotherapy in 155 synchronously treated patients who included 77 STC recipients. Further comparison was made between LTIC and asynchronously treated, comparable control subjects. Although there were side effects and occasional deaths from chemotherapy, they did not alter the operative mortality rate. The over-all 5 year survival rate of the adjuvant LTIC patients was 50.9 per cent, as compared to 22.6 per cent in the asynchronous control subjects (p less than 0.01). For patients who were given LTIC adjuvant to palliative resections the 5 year survival rate was 35.6 per cent, as compared to 4.3 per cent for STC patients or 5.2 per cent for asychronous control subjects (p less than 0.01). Strikingly promising results were obtained from adjuvant LTIC in 10 of 33 patients with undifferentiated cancers. We conclude that LTIC prolonged life among lung cancer patients who were not cured by resection alone. Dual-agent LTIC is safe, apparently beneficial, and worthy of further clinical trials in a research setting.


Lymphocyte responses of lung cancer patients to tumor-associated antigen measured by leucine incorporation.

Lymphocyte responses to lung carcinoma-associated antigens were assessed by measuring 3H-leucine incorporation in 20 lung cancer patients, 37 patients with other neoplasms, and 20 normal subjects. Antigens were prepared from 9 lung carcinomas by means of 3M KCl extraction. Fifteen of 20 lung cancer patients showed increased leucine incorporation to one or more tumor antigens, whereas only 5 of 20 normal subjects responded. Lymphocyte responses to both autologous and allogeneic tumor extracts were observed. Eighteen lung cancer patients were tested with the most reactive antigen and 13 responded. Seven of 37 patients with other neoplasms and 2 of 18 normal subjects reacted to this antigen. Significantly more lung cancer patients reacted to the tumor extract than to an extract of uninvolved lung from the same patient. The reactivity of lymphocytes from lung cancer patients clinically free of disease was significantly greater than that of patients with disseminated disease. Extraction of lung carcinomas with 3M KCl is a useful technique for solubilizing tumor-associated antigens (TAA). Antigenic activity may be followed in vitro by measuring lymphocyte 3H-leucine incorporation.


Cannulation of the proximal aorta during long-term membrane lung perfusion.

Prolonged extracorporeal oxygenator support for acute respiratory failure is a clinical reality. Recent experience with 4 patients has demonstrated an advantage in delivery of saturated blood to the root of the aorta during venoarterial (VA) bypass. We have been able to perfuse the heart and bilateral cerebral hemispheres by advancing the tip of a large perfusion cannula to the aortic root from the common femoral artery. When the catheter did not pass beyond the transverse aortic arch, there was marked asymmetry of oxygenator perfusion, as determined by differential oxygen tension in right and left radial artery blood and by xenon-133 scans following isotope injection into the arterial return line. Long-term VA bypass lasting from 5 to 11 days resulted in long-term survival in 2 patients with post-traumatic gram-negative pneumonitis. The other patients, who had viral pneumonitis and post-transfusion respiratory failure, died after 9 and 11 days of membrane oxygenator support. No embolic lesions or arterial or valvular injuries were discovered at autopsy. This is a safe and useful method of providing oxygenated blood to the aortic root for equal distribution to the rest of the body.


Platelets, hemostasis, and thromboembolism during treatment of acute respiratory insufficiency with extracorporeal membrane oxygenation.

Twenty-eight patients were supported with long-term extracorporeal membrane oxygenation as a treatment for acute respiratory insufficiency. Clinical, laboratory, and autopsy data concerning platelets, hemostasis, and thromboembolic disease are presented for the periods during and after bypass. During bypass, a "foreign-surface coagulopathy" was encountered which consisted of abnormal bleeding plus frequent, generalized, small and large vessel thromboembolic events. The abnormal bleeding is attributed to heparin, thrombocytopenia, and a qualitative platelet defect. Possible causes of the thromboembolic events including disseminated intravascular coagulation are also discussed, and speculations are offered concerning clinical management and directions for future investigation.


Continuous, simultaneous measurement of arterial oxygen tension and arterial blood pressure.

This is an investigation of a technique for simultaneously measuring arterial oxygen tension (PaO2) and blood pressure continuously during and after surgical anesthesia. In 27 patients, a special T attachment was placed on the end of an indwelling arterial catheter so that pressurized dilute heparin could be flushed through continuously while blood pressure was being recorded by means of a transducer-oscilloscope system and PaO2 was being recorded through an indwelling polarograph oxygen tension (PO2) readout device. The electrode was left in the artery for an average of 16 hours; the average PaO2 during mechanical ventilation with the patient breathing 50 per cent oxygen was approximately 200 torr at the beginning of anesthesia; it dropped to 158 torr 6 hours later. The average PaO2 in the recovery room 1 hour postoperatively, with the patient spontaneously breathing approximately 30 per cent oxygen, was 122 torr. No significant complications were encountered during this investigation. We believe this dual technique to be a valuable monitoring tandem in the anesthetized and surgical intensive care patient.


Plasma lipids during extracorporeal circulation.

Total lipids, lipid classes, and per cent composition of fatty acids were investigated in plasma and stored subcutaneous fats of 19 subjects undergoing extracorporeal circulation (ECC). The tests were made before and 3, 20, 40, and 60 minutes after ECC was started. Hemodilution caused a general fall in total lipids and lipid classes. Evaluation of the lipid classes as percentages of the total lipids assumed to be 100 per cent allow the lipid variation due to hemodilution to be disregarded. A linear correlation between an increase in free fatty acids (FFA) and a decrease in triglycerides can thus be observed. This has been attributed to action of the lipase lipoproteic (LLP) activity stimulated by heparin, which is usually employed in ECC hemodilution. The hypothesis that FFA's are mobilized from stored subcutaneous fats was discounted.


Permanent cardiac pacing at a regional medical center.

In our experience with 98 patients, cardiac pacing has proved to be a low risk procedure with an acceptably low incidence of serious complications. Battery depletion requiring pulse generator replacement continues to be the major limitation of this technique. Placement of the pacing catheter within the coronary sinus has not been satisfactory, and measures are routinely taken to avoid this catheter position.


The Blalock-Taussig shunt in the first six months of life.

Because of increasing interest in the application of the Blalock-Taussig shunt in smaller infants, we reviewed the course of 18 infants aged 6 months or less who underwent this procedure. The mortality rate in  4 infants under 2 weeks of age was 50 per cent and that in those 2 weeks to 6 months of age, 28 per cent. The patency rate was 70 per cent. Because of late problems with the Waterston shunt and a comparable mortality rate, the Blalock-Taussig procedure is recommended for all infants, except perhaps those under 2 weeks of age.


Traumatic fistula between left anterior descending coronary artery and right ventricle. Case report with successful surgical repair.

Twelve traumatic coronary artery-cameral fistulas have been reported in the world's literature. Ten have been secondary to penetrating injuries and two have resulted from blunt chest trauma. This case report involves the successful diagnosis and surgical treatment of a patient with a left anterior descending coronary artery-right ventricular fistula. We also discuss similar arteriocameral fistulas previously reported.


Complex of secundum atrial septal defect and congestive heart failure in infants.

Five infants with intractable congestive heart failure due to ostium secundum atrial septal defect (ASD) are presented. All survived ASD closure and are doing well. Correction of this defect in infancy should be considered when medical therapy is unsuccessful.


Dipyridamole and thrombocyte count in open-heart surgery.

The effect of dipyridamole (Persantine) on the thrombocyte count in connection with open-heart surgery and perfusion was studied in 12 patients. A control series of 38 patients undergoing open-heart surgery was available. The dose of dipyridamole, depending on the duration of the perfusion, was 40 to 80 mg. intravenously. We found that dipyridamole definitely had the effect of maintaining the thrombocyte count. At the end of perfusion, the mean thrombocyte count in the dipyridamole group was 129 +/- 20.6 x 10(9)/L. and in the control group 82 +/- 7.4 x 10(9)/L. The result was statistically almost significant (p less than 0.05). At the end of anesthesia the respective mean values were 164.9 +/- 29.7 and 110.8 +/- 8.1 x 10(9)/L. The difference was almost significant (p less than 0.05). The use of dipyridamole did not increase the postoperative hemorrhagic tendency. Our results support the earlier experimental findings that dipyridamole favors the maintenance of thrombocyte counts.


Quadruple valve commissurotomy.

A 12-year-old girl in congestive heart failure was diagnosed to be suffering from severe polyvalvular disease due to a combination of congenital and rheumatic lesions. Cardiac catheterization demonstrated stenotic lesions of all the heart valves. The child underwent quadruple valve commissurotomy and is symptom free and thriving 2 years later.


Postoperative psychosis after heart surgery.

One hundred heart surgery patients were followed throughout their postoperative periods to assess the incidence and etiology of postcardiotomy delirium. Factors evaluated were: age, sex, history of previous psychiatric illness, history of cerebrovascular disease, cardiac diagnosis and operation, time of anesthesia, time of bypass, time spent in the intensive-care unit, and amount of sleep during the postoperative period. Six patients developed delirium, five of whom had a lucid postoperative interval; four patients had perceptual disturbances only, without loss of contact with reality; three had neurological symptoms with mild confusion; 87 kept a clear mental state. The following factors tended to be related to the occurrence of delirium and perceptual disturbances: history of preoperative psychiatric illness, advanced age, severity of preoperative and postoperative illness, and time spent in the intensive-care unit. Sleep deprivation consistently preceded onset of these symptoms with one exception. Operative factors did not seem to be of major importance. While postoperative delirium probably has multidetermined causes, the author believes that sleep deprivation superimposed on the other contributory condition is a common precipitating factor. Suggestions about the prevention and treatment of delirium are made.


The influence of cardiopulmonary bypass on the size of human platelets.

Large and small platelets are present in the bloodstream in nearly equal proportions and comprise about 30 per cent of the normal platelet population. The assumption that cardiopulmonary bypass may alter this platelet population distribution was investigated. Platelet volume distribution curves during and after cardiopulmonary bypass were examined in 12 patients undergoing various intracardiac operation by an electronic particle-sizing apparatus based on the Coulter counter. Mean platelet volume (MPV) was 8.6 +/- 0.7 cubic microns prior to cardiopulmonary bypass. Ten minutes after commencement of cardiopulmonary bypass the MPV decreased to 85 per cent of control levels. A further decrease, reaching a plateau at 75 per cent of prebypass MPV, was reached after 50 minutes on bypass. MPV returned to 87 per cent of prebypass levels 2 hours after discontinuation of cardiopulmonary bypass. Since it is known that platelet count is markedly reduced on cardiopulmonary bypass, a simultaneous 25 per cent decrease in MPV can be explained only by a highly selective disappearance of the large platelets from the circulation. As the larger platelets are younger and functionally more potent than the smaller ones, the selective disappearance of large platelets may thus provide an explanation for the observed alteration in platelet adhesiveness caused by cardiopulmonary bypass.


In vivo strain measurements of a prosthetic aortic valve.

Up to the present, stress forces on prosthetic heart valves have been studied primarily in an in vitro state and have been derived with a fair amount of estimation. Because of the practical and clinical implications, such as forces that may cause fabric wear or material deterioration, we felt that in vivo determination would be worthy of investigation. A microminiature strain gauge was secured to each leg of a non-cloth-covered prosthetic aortic valve and connected to a dual-beam oscilloscope. Strain measurements were first determined in a pulse duplicator with a blood analogue solution and physiological pressures and flow. The valve was also implanted into a dog in the subcoronary position and strain again measured. In vivo strain was found to be approximately 57 per cent of strain on a prosthetic aortic valve, in vitro, under the conditions of this experiment. This represents the first time that strain and force on a prosthetic aortic valve have been determined directly in the intact animal.


Detection of water-to-blood leakages in heat exchangers for cardiopulmonary bypass.

In the construction of heat exchangers, it is of great importance that when they are in use it shall be impossible for water to leak into the blood, as this might lead to hemolysis, intoxications, air emboli, or infection  by microorganisms. In an investigation the aim of which was to discover water-to-blood leakages in the heat exchangers that are generally used during cardiopulmonary bypass, tests were carried out on 17 heat exchangers that are used all over the world and are supplied by five different makers. They included both disposable and nondisposable models. In six stainless steel heat exchangers, water leakages to the blood compartment were detected with the aid of helium. Some of these heat exchangers were brand new and had never been used. The size of the leakages was found to be sufficient to enable them to act as channels for the passage of foreign microorganisms.


Distribution of thymic tissue at the anterior mediastinum. Current procedures in thymectomy.

The distribution of thymic tissue at the anterior mediastinum was examined histologically in 18 cases following the removal of the adipose tissue which was located outside the thymic capsule at the time of thymectomy for myasthenia gravis. The gross adipose tissue revealed the presence of histological thymic tissue, including Hassall's bodies, in 13 of 18 cases. In order to be sure of extirpating all of the thymic tissue, the adipose tissue at the anterior mediastinum as well as the gross thymus should be removed.


The esterolytic activity of poly(1-methyl-4- and -5-vinylimidazole) in water.

The water solubility of poly(1-Me-5-VIm) has made it possible to achieve phenomenal rate enhancements and to gain even greater insight into the mechanism of catalysis by polymeric imidazoles. The poly(1-Me-5-VIm)-catalyzed hydrolysis of S12- exhibited saturation in excess catalyst nad in excess substrate. Inhibition of the poly(1-Me-5-Vim) catalyzed hydrolysis of Sn- type substrates by analog inhibitors was also observed. The saturation apparently did not follow a simple Michaelis-Menten mechanism; however, the results could be rationalized by analogy to certain enzymatic systems. Multisite enzymes have long been known to display kinetic patterns different from that exhibited by enzymes with only one active site, i.e. such phenomena as sigmoidal rate vs [S] plots. These phenomena may arise entirely as a result of the multisite nature of the enzyme. Consequently, a synthetic macromolecular catalyst with multiple sites might also be expected to display such characteristics. The poly(1-Me-5-VIm)-catalyzed hydrolysis of S12- is apparently the first synthetic system in which such phenomena have been observed. The intermediacy of an apolar polymer substrate complex for the poly(1-Me-5-VIm)-catalyzed hydrolysis of S12- in water was given support by studies of the effect of temperature on the rate of hydrolysis. Activation parameters were determined for catalysis by 1,5-DMIm and by poly(1-Me-5-VIm). These results showed that the rate enhancement exhibited by the polymer was due entirely to a favorable entropy term.


The esterolytic activity of poly(N-alkylimidazoles). The effect of ester chain length in the substrate and alkyl chain length in the catalyst on the esterolytic activity of poly(N-alkylimidazoles).

In an effort to exploit the enhancement in catalytic activity which might be derived through hydrophobic interactions between polymeric catalyst and substrate, 1-methyl-5-vinylimidazole (1-Me-5-VIm), 1-methyl-4-vinylimidazole (1-Me-4-VIm), 1-butyl-5-vinylimidazole (1-Bu-5-VIm), and 1-butyl-4-vinylimidazole (1-Bu-4-VIm) have been synthesized and polymerized. In 28.5% ethanol-water, poly(1-alkyl-5-vinylimidazoles)proved to be efficient catalysts for the hydrolysis of various 3-nitro-4-acyloxybenzoic acids (Sn-, where n denotes the acyl chain length). Order of magnitude rate enhancements, as compared to the model compound, 1,5-dimethylimidazole (1,5-DMIm) were observed in the poly(1-alkyl-5-vinylimidazole)-catalyzed solvolysis of S12- and S18-. Poly(1-Me-5-VIm) catalyzes the hydrolysis of S18-88 times faster than does 1,5-DMIm. The poly(1-Me-5-VIm)-catalyzed hydrolysis of S18- in ethanol-water was analyzed in terms of a simple Michaelis-Menten type mechanism. Vmax and Km were determined to be 40.2 X 10(-7) M min-1 and 2.20 X 10(-5) M, respectively.


The determination of chain statistical parameters by light scattering measurements.

The effects of volume exclusion on polymer chain conformations can be determined from the study of the angular dependence of radiation scattered by chain molecules. It is found that useful information can be obtained only when the variable x is large, where x is the product of the square of the magnitude of the scattering vector and of the mean square radius of gyration. Hence, solutions of macromolecules of very high molecular weight are needed for these investigations. The theoretical treatment of the scattering function is based on several assumptions. The validity of these assumptions is examined by computing, using a Monte-Carlo technique, various moments of intramolecular separations and comparing the results so obtained, in the limit of a chain of infinite length, with the analytical results. The computations seem to verify the validity of the theoretical model. The scattering behavior of solutions of recently synthesized polystyrene of Mw = 4.4 X 10(7) in cyclohexane at various temperatures and in benzene at 40 degrees was investigated. From the log-log plots of the scattering function vs. x, a statistical parameter was calculated, whose value depends on the magnitude of long-range correlations between any pair of chain elements. It is found that above the theta temperature this parameter is practically independent of temperature and that its numerical value was found to agree well with the value obtained from Monte-Carlo calculations. In the neighborhood of the theta temperature, this parameter decreases rapidly with decreasing temperature, indicating a first-order transition in chain conformation.


The effect of neighboring charges on the helix forming ability of charged amino acids in proteins.

It has been found that the fraction of glutamic acid residues which are helical in proteins is larger than might be expected from the experimentally determined value of the helical stability constants of glutamic acid. In order to understand this difference, the effect of neighboring charged side chains on the glutamic acid residues in proteins of known structure is examined. It is found that a positively charged side chain four residues away from a glutamic acid greatly enhances its probability to be helical. Similar results are obtained for aspartic acid, lysine, arginine, and histidine.


Theory of the cooperative transition between two ordered conformations of poly(L-proline). I. Phenomenological theory.

The states of three residues are correlated in a nearest-neighbor Ising model matrix treatment of a one-dimensional phase transition, in which nucleation is assumed to differ at each end of a regular sequence (asymmetric nucleation). The correlation of the states of three residues requires a 4 X 4 matrix, which cannot be reduced in size because of the asymmetric nature of the nucleation. Also, because of the asymmetry, at least four independent parameters for a homopolymer (rather than the two usually encountered in the helix-coil transition), ant at least five for a specific-sequence copolymer, are required to describe the transition behavior. The most important current interest in such a treatment (for a homopolymer) is its applicability to the poly(L-proline) form I in equilibrium form II interconversion. The earlier treatment of Schwarz, using the nearest-neighbor Ising model (with correlation of only two residues), is identical with the above treatment, and requires only a 2 X 2 matrix which greatly simplifies numerical computations, which are presented in the next two papers of this series. However, the 4 X 4 matrix treatment is required in order to make the asymmetric nature of the nucleation explicit and physically understandable, for a homopolymer; for a specific-sequence copolymer, such as a protein, it is essential in order to show how the asymmetric nature of helix nucleation differs from one amino acid to another.


Theory of the cooperative transition between two ordered conformations of poly(L-proline). II. Molecular theory in the absence of solvent.

Phenomenological theories of the transition between helical form I (cis peptide bond) and helical form II (trans peptide bond) of poly(-L-proline), which is a typical order in equilibrium order transition, have been presented by Schwarz (using the parameters s, sigma, beta', and beta'' in a 2 X 2 matrix formulation) and by the present authors (using the parameters s, sigma betaC, and betaN in a 4 X 4 matrix formulation). A molecular theory of the same transition has been formulated to account for the phenomenological parameters. The statistical weights of regular helical sequences with and without junctions between the two forms were computed from empirical potential energy functions. Two puckering conformations of the pyrrolidine ring, i.e., with the Cgamma atom down and up, were allowed, and the free energy was computed for chains with four types of puckering, viz., regular down, regular up, random A, and random B, in the latter two of which the up and down puckerings were randomly distributed. The random A and random B chains have higher energy than those with regular down or up puckering, in both forms I and II. From both an energetical and a free energetical point of view, form I is more stable than form II under vacuum at room temperature. The dependence of the relative stabilities of form I and form II under vacuum on chain length was examined from both an energy and free energy point of view. The four parameters, s, sigma, beta', and beta'', which describe the transitions in Schwarz's theory, were calculated from the statistical weights of various types of sequences. It was found that the thermally induced transition between form I and II under vacuum occurs with the pyrrolidine rings remaining in the down conformation. The calculated values of s suggest that form I is more stable than form II in the regular down chain, while form II is more stable than form I in the regular up chain under vacuum at room temperature. The calculated values of sigma for regular down and regular up pyrrolidine ring puckering are in good agreement with experimental observations, whereas those for random A and random B puckering are much smaller than the experimental values. A theory for the effect of solvent on the parameters s, sigma, beta', and beta'' (at constant temperature) is developed, and the computations involving solvent effects are described in the next paper.


Theory of the cooperative transition between two ordered conformations of poly(L-proline). III. Molecular theory in the presence of solvent.

Phenomenological theories of the form I in equilibrium to form II interconversion in poly(L-proline) have been presented by Schwarz (using the parameters s, sigma, beta', and beta'' in a 2 X 2 matrix formulation) and by the present authors (using the parameters s, sigma, betaC, and betaN in a 4 X 4 matrix formulation). In addition, a molecular theory was developed to compute s, sigma, beta', and beta'' under vacuum. In this paper, we take into account the effect of solvent on the parameters s, sigma, beta', and beta'' of the isothermal poly(L-proline) form I in equilibrium to form II interconversion. The growth parameter is sensitive to the binding of solvent molecules to the peptide CO groups, but the nucleation parameters sigma, beta', and beta'' are not affected by this type of solvent effect. The calculated values of s and sigma under vacuum are in good agreement with the corresponding values derived from experimental data. By combining the theoretical values of s, sigma, beta', and beta'' under vacuum with experimentally determined equilibrium constants for the binding of alcohols to the peptide CO groups (which differ in magnitude for form I and form II), it was possible to reproduce the experimental tranistion curves satisfactorily. Alternatively, the binding constants for alcohols, obtained by combining our theoretically computed parameters under vacuum with experimental equilibrium transition curves, are in a satisfactory agreement with those evaluated independently by infrared spectral measurements of the binding of alcohols to the peptide CO groups. It is pointed out that significant errors may arise in analyzing experimental data if short chains are included with long chains in the determination of s, sigma, beta', and beta'' from the equilibrium transition curves. The transition of poly(L-proline) from form II to form I when n-butyl alcohol is added to a solution of the polymer in benzyl alcohol is brought about by the slight difference in the binding free energies of both alcohols to the carbonyl groups of form II. The different binding affinities of two alcohols, ROH, to form II may arise from (a) the different hydrogen-bond strength between the alcohol and the proline carbonyl group, and (b) possible differences in nonbonded and electrostatic interactions between the R group and the binding-site environment of the proline carbonyl group. The greater binding affinity of form II (compared to form I) for given alcohol is attributed to the more open and extended conformation of form II.


A general treatment of the configuration statistics of polysaccharides.

A treatment of the configurational statistics of polysaccharides is given in the isomeric state approximation. All classes of linear polysaccharides of specifiec chemical sequence are treated simultaneously. Chain tortuosity arising from torsional motions about the chemical bonds of the glycosidic linkages is recognized explicitly as is the possibility for conformational isomerism of the sugar residues. Valence angles and lengths are taken to be fixed at the equilibrium values, and pyranose residues in their chair conformations are treated as inflexible constituents of the skeletal structure. Pyranose and furanose forms capable of pseudorotation may be incorporated as rigid skeletal entities as well, provided suitable attention is given to the selection and interpretation of the conformational isomeric states included. Separation of the configuration energy into independent contributions is shown to be impossible in general. Methods are described for assessing the influence of neighbor interactions on the populations of the several conformers of the sugar residues. The relative conformational free energy of the flexible and chair form conformers of pyranose sugars is discussed, and appropriate measures of polysaccharide chain flexibility and stiffness are suggested.


Kinetics of helix-coil transition in all sizes of polypeptides.

The relaxation behavior of the helix-coil transition has been investigated for all sizes of polypeptides. Unlike previously reported results, regardless of the size of polypeptides, the first-order kinetics plays a principal role in the relaxation process when a helical state is relaxed to a half-coiled state [i.e. s(f) is congruent to 1, where s(f) is the helix stability parameter at the final state]. On the other hand, when a helical state is relaxed to a coiled state [i.e., s(f) is less than 1], the zeroth-order kinetics plays a major role. In addition, the range of the validity of a kinetic version of the zipper model has been investigated. We have found that when a helical state is relaxed to a state where s(f) is less than or equal to 1, the zipper model is valid for polypeptides with chain length N satisfying the relation N is less than 1/(sigmagammaC)1/2 where sigma is the cooperativity parameter and gammaC is the coil nucleation rate parameter.


A health status assessment system for a rural Navajo population.

An analysis of the first year's operation of an ambulatory patient monitoring system is presented. The program was designed to accomplish the following objectives: 1) to demonstrate individual clinic effectiveness in giving each member of its service population a complete assessment of his health status, and 2) to implement patient surveillance for follow-up and periodic reevaluation. The system was adapted to the pre-existing computer-based ambulatory patient care reporting mechanism which is in use by Indian Health Service members and contracting facilities. It employs discrete health status categories whose definitions are based in specific clinical criteria. This approach permits the interpretation of categorical patient flow statistics as representative of identifiable clinic practices. Quarterly data printouts provide a basis for interpreting the degree of clinic progress toward initial health assessment of the total population served. Such data, when viewed against the backdrop of specific operational objectives allow for continuous program reassessment of community needs, and provide a technique for monitoring the effectiveness of the health care delivery system in meeting these needs. By controlling for individual variations in clinic objectives, comparisons can be made between separate facilities within the network. In addition, the technique provides a method for focusing on areas where objectives may not be realistic and provides a data base on which alternative program goals can be formulated.


The men in the middle: a dilemma of minority health workers.

The perception of Indian health care needs are shown to be related to particular positions within the Public Health Service (PHS) structure. This study is based on interview data gathered from three groups: Navajo consumers (N = 271), Navajo PHS personnel (N = 80), and PHS non-Navajo professional staff (N = 31). The identification of health needs by the Navajo consumer is oriented toward unsolved problems in the immediate social and physical environment. Ninety-five per cent of the problems identified by the consumer centered around disease states, alcoholism, environmental problems, and transportation. Only 28 per cent of the Navajo personnel responses fell within these categories. The responses of the professional staff were systematically distributed among 14 identified health needs. Of major concern is the marginal position held by the Navajo PHS employee who seems to identify health problems which are similar to neither the Navajo consumer nor the PHS professional. While they are still tied to the Navajo culture per se, the Navajo personnel are economically dependent upon the PHS for a livelihood. This "man in the middle" position may require divided loyalties-to their community and to their employer. Such a schism can have serious consequences in their ability to function effectively as health workers.


Converting child health stations to pediatric treatment centers.

Nineteen child health stations in New York City have added treatment services to their traditional role of well-child supervision with the objective of increasing the access of children livine in underserved areas to integrated preventive and therapeutic care. The conversion process was studied at nine pediatric treatment centers (PTC) in upper Manhattan and the South Bronx. the Department of Health accomplished the conversion by adding full-time pediatricians, on-premises laboratory capability, prepackaged pharmacies, and informal arrangements with local hospitals. The proportion of patient visits at the PTCs for sick care ranged from 11 to 57 per cent and varied with the length of time the unit had been in operation. Personnel cost per visit was $16. Six child health stations were compared before and after conversion to PTCs. Registration increased 5 per cent, visits increased 50 per cent, and personnel cost increased 150 per cent. Review of 600 patient visits revealed that the majority of illness visits were for minor conditions, notably upper respirtory infections. Interviews of 600 parents of three PTCs revealed that approximately one-fourth regarded the PTC as a usual source of care. Increased access and continuity of child health services have been accomplished by these conversions. Adding treatment services to child health stations is a satisfactory alternative to the overcrowded hospital-based pediatric facility.