Lithium intoxication. (Report of 23 cases and review of 100 cases from the literature).

Twenty-three patients were studied, 21 of whom developed intoxication during maintenance therapy with a lithium dosage which had been unchanged for months to years. Toxic effects on brain, heart and kidneys were found and the severity of lithium intoxication seemed to depend on at least three factors: the height of the serum lithium concentration (SLi), the duration of lithium intoxication and individual tolerance. Disorders of water and electrolyte metabolism preceded lithium intoxication in the majority of the patients. Water loss due to impaired renal concentrating ability seemed to be a major predisposing factor. Renal insufficiency was apparent in 17 of the patients on admission and five of these did not regain normal renal function. In seven patients, renal biopsy showed abnormalities which suggest that a chronic nephropathy, possibly caused by lithium, might be another predisposing factor. Treatment with sodium chloride infusion had no specific effect on lithium excretion and led to hypernatraemia in some patients and is therefore not recommended. Hemodialysis is the most effective method available for removing the lithium ion from intoxicated patients. Hemodialysis should be carried out long enough to secure a SLi of less than 1 mmol/l after redistribution of lithium in the body. Treatment by peritoneal dialysis is appropriate only if hemodialysis facilities are unavailable. Lithium intoxication is a serious condition. Of the 23 patients reported, two died and two developed persisting neurological sequelae. The best way to prevent lithium intoxication is to control the serum concentration and to assess renal function and renal concentrating ability regularly during therapy.


Echocardiographic evaluation of pericardial diseases.

This review has attempted to summarize the usefulness of echocardiography in pericardial effusion and other pericardial diseases. As stated before, it is an extremely useful technique for the detection and following of patients with pericardial effusion. The usefulness in other forms of pericardial disease is less well-established.


Functional heterogeneity of rabbit peritoneal and alveolar macrophages activated with Mycobacterium bovis BCG.

The biological activity of rabbit peritoneal and alveolar macrophages activated with M. bovis BCG was investigated by use of tests measuring their phagocytic and staphylocidal properties. Macrophages were separated in a discontinuous albumin gradient which yielded 4 to 5 bands depending on the source of the exudate. The peritoneal exudate had about 40% of cells recovered in band E and the alveolar exudate had about 35% in band C. There were not significant differences between the uptake by three subpopulations of macrophages. The alveolar macrophages from normal rabbits were less active than peritoneal macrophages. They were also less active those from vaccinated animals. Subpopulations of band B macrophages killed S. aureus more efficient than those from band C. Such differences reflect the number of mature or immature cells in each subpopulations. Mature cells (bond B and C) possess phagocytic and bactericidal activities whereas immature cells (bond D) are capable of ingesting bacteria but no killing them.


[José Martins da Cruz Jobim: his priority in the detection of an hereditary hematologic disorder in African Negro slaves (author's transl)].

A brazilian physician, José Martins da Cruz Jobim, may be considered the author of one of the earliest medical reports with a story of the prevalence of the sikle cell trait among african negroes who came to Brazil as slaves, by observing their rather remarkable resistance against malarial infections than other sets of our population. Naturally, his report, published in 1835, must be considered by the actual scientific concepts.


[Nucleic acid and proteins content in Trypanosoma cruzi epimastigotes].

The nucleic acids and protein content in epimastigote forms of Trypanosoma cruzi during its exponential growth in vitro were studied. The parasites were cultivated in a diphasic blood-agar medium at 28 degrees C. The RNA extraction and hydrolisis were performed by the method of Fleck and Begg and the acid hydrolisis of DNA precipitate was done according to Webb and Lindstrom. Schneider's colorimetric method was used for ribose and desoxyribose measurement, employing as reagents orcein and diphenylamine respectively. Protein content was determined by the method of Lowry et al. Calf thymus DNA, yeast RNA and bovine plasma albumin were used as standards. It was established that 1.00 g of wet parasites contained 1.05 (+/-0.17) X 10(10) epimastigote forms. The contents of DNA, RNA and protein were 6.1, 12.3 and 105.4 mg/g of wet epimastigote, or 5.8, 11.7 and 100.1 X 10(-7) microgram per epimastigote, respectively. The method employed for nucleic acid determinations did not show great differences when compared with the Schmidt Thamhauser-Schneider technique, and it has the advantage of being more rapid.


[Research of toxoplasmosis by intradermal reaction in suspected cases].

Toxoplasmosis was diagnosed in 5i,2% of 5000 patients and cohabitants with suspicions of several affections who were referred to the parasitology service of the "General Calixto García" Teaching Hospital from several provinces and regions of the country. The intradermoreaction test with toxoplasmin antigen was used in all of them. Results are exposed according to affections, sex, age and origin of the patients.


[Otic myiasis in a newborn caused by Calliphoridae larvae of the genus Phaenicia].

A 55-day-old newborn with an intense otitis haemorrhagica caused by a Calliphoridae larva of the genus Phaenicia is presented. During an ear lavage the larva was removed. The patient was admitted and once the genus was known he underwent a specific treatment and was discharged completely cured.


[Homogenization of samples for the culture of mycobacteria. A comparative study of samples with and without centrifugation].

A homogenization method for sputum samples for the culture of acid-fast bacilli that omits the use of centrifugation, passage test tubes and balances is described. 10% sodium phosphate was used as decontaminating substance. This method facilitates the laboratory work since the samples so treated are incubated at 37 degrees C up to the next day when they are then cultured.  676 samples prepared according to this method were compared with samples prepared according to the standard method; a 6,21% positivity in the former compared to a 5,47% in the latter as well as a lower percentage of contamination were obtained. Contamination occurred in 9,91% of samples without centrifugation and in 14,35% of centrifuged samples.


The transseptal approach to the pituitary gland.

Transseptal, transsphenoidal pituitary surgery is safe and effective in the management of various problems associated with the region of the sella turcica. This series include 285 operations on 272 patients treated from Sept. 1, 1972, to Sept. 1, 1976. The operative mortality was 1.75%. In every patient, the anatomy should be assessed preoperatively by polytomograms of the sella and the sphenoid sinus and by bilateral carotid angiography. The operating microscope and intra-operative x-ray control with the image-intensifier are essentials. Pneumoencephalography is performed whenever the possibility of an empty sella or arachnoidal cyst exists and when angiography does not satisfactorily outline the suprasellar extension of large pituitary tumors. Computerized tomographic scanning is also of value. A new group of pathologic problems, namely microadenomas (tumors less than 1 cm in diameter), has now become amenable to transseptal surgical management. This series includes a group of 50 patients with microadenomas: 45 with functioning pituitary adenomas and 5 with nonfunctioning pituitary adenomas. The transfrontal intracranial surgical approach also has specific indications. This choice is determined by the anatomy and the extent and nature of the pathologic lesion. The rhinologic concepts of exposure and reconstruction are modifications of the "maxilla-premaxilla" (Cottle) approach to the nasal septum. This allows direct midline access to the sphenoid sinus and sella turcica while preserving both the caudal end of the nasal septum and the anterior nasal spine, thereby minimizing rhinologic airway and cosmetic complications. We believe that, by combining the talents of the neurosurgeon, endocrinologist, neuroradiologist, ophthalmologist, and rhinologist, this procedure can be offered to patients with a wide range of disorders and excellent results may be anticipated.


[Allergies and dental pulp (author's transl)].

A review of the articles dealing with allergy in the dental pulp is oppered. The dental pulp--furthermore when inflamed--showes antigens, lymphocyetes and plasmocytes, antibodies (IgG, IgA and IgE), mast-cells, histamine and possibly C3. However an hypersensitivity or allergy of immediate type elicited by circulating antibodies has never been demonstrated. In another way, two types of allergies of cellular type have been described in the dental pulp: graft rejection and contact hypersensitivity. Autoimmunity has also just been described.


On the theory of an intravenous isotope method for cerebral blood flow measurements.

The theoretical basis of the intravenous isotope method has been examined with particular emphasis on the physiological significance of the area of the curves obtained and the meaning of the peak activity. It is concluded that the area is proportional to the volume of distribution of the indicator within the monitored volume, and inversely related to the cardiac output. The peak activity will be a measure of the fractional blood flow to the brain. It will be affected, however by the extension of the input bolus to the brain but also by the transit time within the brain itself. An unexpected low cardiac output, for instance, will lead to an over-estimation of the cerebral blood flow as derived from the peak activity even though the concomitant prolongation of the input bolus will reduce the error. The theory thus suggests that central circulatory variables will have an influence on the curves obtained and thus also will influence the validity of the method. The validity can be substantially improved by (1) the determination of the input bolus by, for instance, a gamma detector focused over the aortic arch, and (2) by the determination of the cardiac output; this can theoretically be carried out if a true intravascular indicator is used and the investigation is expanded to include the determination of the systemic blood volume.


The validity of an intravenous isotope method for cerebral blood flow measurements. An experimental study.

The intravenous isotope method has been examined. The method uses 99Tc as the indicator with recording of the radioactivity with two gamma-dectors placed bilaterally over the skull and oriented over the bifurcation of the middle cerebral artery. 65% of the total curve obtained was found to be generated by activity passing in the ipsilateral internal carotid artery, 25% in the contralateral internal carotid artery and less than 10% by activity passing in the two external carotid arteries. The counting rate efficiency for an intracerebral location was 19.4 +/- 1.8 times the count rate from the same activity placed at 1 m distance in air which in turn was 5 cps/muCi. The variability in efficiency from patient to patient was thus estimated at +/- 9%. The duration of the input bolus had a marked influence on the vurve, which will be of importance since it showed a rather large variability from patient. Using the peak activity as an index of the cerebral blood flow the intravenous method showed a surprisingly good correlation with the 133Xe wash-out method; the correlation coefficient was 0.93 and the variability at slightly subnormal values estimated at +/- 15%. It is concluded that the method can be used in the case of limited demands on the accuracy of the cerebral blood flow determinations.


[Primary intraorbital meningiomas].

The authors found in literature the description of 124 cases of intra-orbital primitive meningiomas; they illustrate their clinico-surgical aspects as well as the differential features on the ground of their point of origin: 90 meningiomas of the (dural) sheath of the optic nerve (23 intraforaminal ones and 67 extraforaminal ones), 34 extradural meningiomas; they present 4 original cases, 3 extradural ones and 1 of the sheath of the optic nerve. After describing the elements of differential diagnosis with the most common intra-orbital expansive lesions (gliomas, sarcomas, angiomas, psuedotumors or orbital granulomas) the authors end by stating that total extirpation must be always carried out including, if necessary, the optic nerve and the ocular globe when it is invaded.


Glucose tolerance in relation to skeletal muscle enzyme activities in cancer patients.

Glucose metabolism and skeletal muscle enzyme activities were studied in nineteen cancer patients and twelve matched controls. The fasting insulin values were normal but the fasting glucose values and the sum of glucose were increased and the sum of insulin was decreased during intravenous glucose tolerance test in the cancer patients. The elimination rate of glucose (k-value) during glucose challenge was, however, not significantly different in cancer patients as compared with that of appropriate controls. The activities of enzymes representative for glycogen turnover, glycolysis, citric acid cycle and respiratory chain were significantly lower in the muscle tissue of cancer patients, while the activity of 3-hydroxyacyl-CoA dehydrogenase, an enzyme in the beta-oxidation of fatty acids, was unchanged and the activity of glucose-6-phosphate dehydrogenase was significantly higher. Rate limiting enzyme activities in muscle tissue, phosphofructokinase and cytochrome c oxidase correlated signficantly with plasma insulin and glucose during glucose challenge. The results point at the possibility of covariating debilitation of pancreatic beta-cells and skeletal muscle enzymes caused by the malignant tumour.


The significance of body sodium content in hypertension following renal transplantation: exchangeable sodium and plasma renin concentration before and after renal transplantation.

The purpose of the present study was to determine the importance of body sodium content in hypertension following renal transplantation using measurements of exchangeablesodium (NaE) before and after transplantation. Plasma renin concentration (PRC) was also investigated. In the present study the necessity of a reference for expressing NaE values was eliminated because the subjects investigated acted as their own controls. The study included fourteen recipients, of whom seven were normotensive with an average blood pressure (BP) of 136/84 mmHg and seven were hypertensive with an average BP of 182/113 mmHg after renal transplantation. In the hypertensive NaE increased significantly (mean 22%) in contrast to an insignificant decrease in NaE in the normotensives (mean, -5%). The change in NaE was positively correlated to the mean BP after renal transplantation (p = 0.69, n = 14, P less than 0.02). BP and NaE were not correlated to prednisone dosages. PRC was normal in all the hypertensives. The results strongly suggest that sodium accumulation in the body, which is not prednisone-dependent, is involved in the pathogenesis in post-transplant hypertension.


A method for the assessment of placental blood perfusion using 99mTc pertechnetate.

A radioisotope method was developed for the measurement of placental blood flow using 99mTc pertechnetate as a tracer and a single detector as a measuring device. The results are given as placental perfusion rate (ml/min/ml) calculated from the tracer-appearance curve. The series consisted of 148 healthy pregnant women between the 28th and 42nd week and fifty pregnancies with a hypertensive disease. In healthy subjects the placental perfusion rate increased by about 32% in the period between 28th and 38th week, but there was a large variation. The perfusion rate showed a tendency to diminish at term. In a group of fifty hypertensive pregnancies a highly significant decrease in the perfusion rate was observed when compared with normal subjects. The conclusion drawn is that this method can be used for the quantitative measurement of placental blood supply.


A radioimmunoassay of the pregnancy-specific beta1-glycoprotein (SP1).

A radioimmunological method for determination of the pregnancy specific beta1-glycoprotein (SP1) is described. Antigen specificity of rabbit anti-human SP1 serum (Behringwerke) was investigated against human placental and pituitary hormones. The sensitivity was about 10 microgram/l. The concentration ranges of SP1 in umbilical cord blood and amniotic fluid were 0.10--0.60 mg/l and 0.3--3.8 mg/l, respectively. A good correlation (r = +0.95) was found between the radioimmunological and electroimmunological methods for determination of SP1 in maternal blood.


Effect of rat intestinal glycoprotein on complement lytic activity of 32P-labelled Escherichia coli.

Evidence for complement activation by an intestinal glycoprotein fraction from germfree rats is presented. The lowering effect on human serum bactericidal activity of E. coli was 28% for the intestinal glycoprotein fraction, 31% for zymosan, and 25% for inulin, while the lowering effect on conventional rat serum bactericidal activity was 65%, 53% and 21%, respectively. 32P-releasing activity of serum from germfree rats and from man on labelled E. coli amounted to 8% and 28%, respectively, of the release exerted by serum from conventional rats.


Characterization of lymphocytes isolated from non-lymphoid human malignant tumours.

Mononuclear cells (MC) were found in suspensions prepared from twenty-one out of twenty-two solid human neoplasms. In three cases it was calculated that more than 1% of the MC could represent contamination by blood MC. Due to technical difficulties and blood lymphocyte contamination, eight cases were excluded from the study. MC could be separated from thirteen of the remaining fourteen tumours and in one tumour no MC were found. On average, 0.44 X 10(6) MC were obtained from each biopsy weighing 1-5 g. The MC were characterized with regard to markers for T and B lymphocytes. On average 41.0% of the MC were T and 18.2% B cells. There was no significant correlation between MC infiltration and tumour size or spread. In all patients blood MC were also isolated and characterized with regard to T (62.0%) and B lymphocytes (14.3%). The T/B ratio of tumour and blood lymphocytes corresponded in most cases. In two cases a markedly depressed T fraction was found within the tumour, whereas the T lymphocyte portions in the blood of these patients were within the normal range.


beta-lactamase insensitive or inhibitory beta-lactams: two approaches to the challenge of ampicillin-resistant E. coli.

The rising incidence of Gram-negative bacteria resistant to ampicillin in hospitals has brought about a need to develop novel beta-lactam antibiotics. This challenge is being met in two ways. First, attempts have been made to develop compounds insensitive to beta-lactamase hydrolysis. This has proved difficult in the penicillin series, but cefuroxime and cefoxitin are cephalosporin derivatives with the necessary properties. The second approach has been to discover novel beta-lactam nuclei capable of inhibiting beta-lactamases. So far this had led to the production of the clavulins and the olivacins, the latter class of molecules being closely related chemically to thienamycin.


beta-lactamase production by strains of Escherichia coli of intermediate susceptibility to beta-lactam antibiotics. A study of their clinical significance in urinary tract infection.

In a prospective study of patients treated with cephalexin or co-trimoxazole, almost all isolated E. coli strains of intermediate susceptibility to ampicillin or cephalosporin (MIC 2-16 microgram/ml) were shown to produce beta-lactamase detectable with a chromogenic cephalosporin substrate, or by the clover-leaf test or the acidimetric method. When assayed in preparations of sonicated bacteria, the enzyme had a cephalosporinase-substrate profile in a large majority of cases. In order to evaluate the clinical significance of this beta-lactamase production, 48 patients with urinary tract infection (UTI) were treated with cephalexin, an antibiotic hydrolysed by the enzyme. Forty-three additional patients were treated with co-trimoxazole for comparison. A statistically significant difference in cure rate (p less than 0.05) was found after 2 weeks. Six recurrences occurred in the cephalexin group and none in the co-trimoxazole group. However, after six weeks there were 8 and 5 recurrences, respectively (p less than 0.05). There were no differences in beta-lactamase activity or MIC/MBC between initial strains and isolates from recurrent UTI. Thus, the recurrent infections were not due to emergence of resistance.


Effects on renal function of treatment with cefoxitin alone or in combination with furosemide.

The glomerular filtration rate measured by 51Chrome-EDTA and serum half life of cefoxitin were followed in patients with preexisting moderate renal impairment. The patients were treated with cefoxitin for two to three weeks because of chronic serious infections. The dose used in patients with an initial clearance of more than 40 mg/ml was 1 g three times daily giving a mean peak concentration of 100 microgram/ml. Seven patients were treated with cefoxitin alone and twelve with cefoxitin and furosemide (80 mg daily orally). The glomerular filtration rate did not change significantly during treatment time. There were no signs of accumulation of cefoxitin as serum half life of the drug remained unchanged both in patients treated with and without furosemide concurrently.


Newer cephalosporins and cephamycins--a review.

Since the introduction of cephalothin and cephaloridine as the first parenteral cephalosporins and cephalexin as the first member of the group which is absorbed from the gastrointestinal tract, several new cephalosporin derivatives have been developed. Most of these have no major advantages over cephalothin, cephaloridine or cephalexin. Increased knowledge about the importance of beta-lactamases for bacterial resistance against beta-lactam antibiotics has focused interest on development of drugs with increased resistance to degradation by these enzymes. Among the caphalosporins, cefamandole and cefuroxime have been found to be markedly more active against beta-lactamase producing Gram-negative bacteria. A new group of beta-lactam antibiotics, the cephamycins, have been introduced with cefoxitin as the first clinically useful member. Cefoxitin has the spectrum of a beta-lactamase-resistant cephalosporin and is also active against Bacteroides fragilis. The review concentrates on the antibacterial spectrum of these three new antibiotics and on their clinical efficacy.


Renal transplantation in patients with diabetic nephropathy.

Renal transplantations were performed over a period of three years to twenty patients with end-stage diabetic nephropathy. Two of the patients were transplanted with kidneys from living donors, others with cadaver kidneys. One year after the transplantation 6 patients out of 12 were alive, after two years one out of four. Graft survival after one year was 4 out of 12, and after two years one out of four patients. Eight patients had died, the primary causes of death having been infection or infarction. Late complications in the form of gangrene occurred in four patients with a functioning transplant. The issue of priority, criteria for selection, and the use of living donors are discussed.


Diabetic nephropathy. Clinical observations and prognosis.

38 diabetic patients in dialysis or after renal transplantation have retrospectively been studied to see if some of the clinical observations could be of prognostic value. The results show that cardial ectasia is correlated to a significant higher mortality, whereas the degree of diabetic retinopathy and the duration of diabetes both seem to be without prognostic importance.


Diabetic nephropathy. Experiences through seven years. Survival curves and causes of death.

A 7-year material is presented comprising 38 diabetic nephropathy patients who were treated by dialysis and transplantation. The cumulative patient survival rate after one year is 39%. The survival rate of the transplanted diabetic patient is poorer than that of the transplanted non-diabetic patient. However, no difference is to be found between the graft survival rates of the two patient groups. Forty-seven percent of the patients died from cardiovascular causes and 43% from infectious complications.


Factors influencing the prognosis in diabetic patients accepted for renal transplantation.

Out of 27 patients with advanced diabetic nephropathy accepted for renal transplantation. 11 had cardiac symptoms and 10 others had advanced neuropathy. The former group had a poor outcome with 100% mortality within one year, seven patients dying before transplantation. Neuropathy also indicated a poor prognosis. Early transplantation, before the stage of terminal uraemia, was at no advantage in this material.


Kidney transplantation in diabetic nephropathy: four years experience.

Since 1972 65 patients with diabetic nephropathy have been evaluated for renal transplantation. Twenty one were not accepted, 6 died before transplantation and 10 are still under observation. Of 28 transplanted patients 13 are alive with functioning graft, and 3 are treated with hospital dialysis. Patient survival at one year was 65% and graft survival 50%.


Bone lesions following renal transplantation. Bone mineral density and amount of trabecular bone.

24 renal transplanted patients who developed post-transplant bone complications (aseptic necrosis of bone of spontaneous fractures) were studied and compared with a control material of age- and sexmatched renal transplanted (RT) patients. The bone mineral concentration in the forearm, histomorphometric measurements of iliac crest biopsies, and the parathyroid function were investigated. A significant reduction in the bone mineral concentration was found in the group of RT patients with bone complications compared to RT patients without. The amount of cancellous bone in the bone biopsies was reduced in patients with aseptic necrosis of bone. No significant differences in the biochemical values were found.


The clinical significance of hyperparathyroidism after renal transplantation.

Hypercalcemia after renal transplantation (post-TH) was detected in 32 (17%) of 188 long-term survivors. The mean time from renal transplantation (RT) till onset of post-TH was 60 (3-210) days. In 19 patients the hypercalcemia was mild and transient, resolving spontaneously within 1-65 (mean 18) months. In 6 patients s-calcium normalized simultaneously with a rejection episode treated with increased prednisone doses. The hypercalcemia was more pronounced (permanent) in 7 patients, and terminated by subtotal parathyroidectomy in 5 and still persists in 2. The hypercalcemia was asymptomatic and did not affect the function of the graft except in one patient who developed calculi in the graft and a fall in graft function, all of which disappeared after subtotal parathyroidectomy. The frequency of aseptic bone necrosis and spontaneous fractures was the same in recipients with and without post-TH. Serum parathyroid hormone (s-PTH) was significantly higher in patients with permanent than in those with transient post-TH, who had the same slight elevation of s-PTH as the normocalcemic recipients. A permanent course of post-TH can be expected when both s-calcium and s-PTH are persistingly elevated.


Parathyroidectomy after renal transplantation.

Among 569 patients treated with renal transplantation during a 12-year period in Gothenburg, eleven patients were subjected to subtotal parathyroidectomy after successful transplantation. All patients had comparatively long histories of advanced renal failure and/or long-lasting haemodialysis treatment before transplantation. Signs of hyperfunctioning parathyroid glands (elevated total serum calcium with or without clinical symptoms) appeared within the first few months after transplantation in eight cases, and after 1-3 years in three cases. Four patients had symptoms of bone disease and/or soft tissue calcium deposits whereas renal functional impairment was not noted in any patient. The remaining seven patients were operated upon because of persistently elevated serum calcium levels only, in order to prevent such complications. In spite of our extremely restrictive policy concerning parathyroidectomy in patients awaiting renal transplantation and, conversely, a liberal attitude to this operation after transplantation, parathyroidectomy was a rare event among our patients. The rationale for surgical treatment of mild hyperparathyroidism following renal transplantation is questioned, as is the need for sophisticated diagnostic procedures to detect more cases of asymptomatic hyperparathyroidism.


Hyperparathyroidism in uremia and after kidney transplantation.

From 1969 until the end of 1976, 376 patients have had kidney transplants in our department. Fourteen patients have had subtotal parathyroidectomy done, either in their uremic phase or after a successfull kidney transplantation. All patients, except one, who had an adenoma, had varying degrees of hyperplasia of the glands. The postoperative results were satisfying in 10 patients. 3 patients is medically substituted for hypoparathyroidism while one still is hypercalcemic. There was no operative mortality and no surgical complications.


Secondary hyperparathyroidism and parathyroidectomy in terminal chronic renal failure.

Subtotal parathyroidectomy was performed on 34 patients with severe renal insufficiency. The indications were grave clinical symptoms (pruritus, bone pains and mental disturbances), gastric ulcer and radiological abnormalities (metastatic calcifications, osteoporosis, fractures and subperiostal resorption). The serum calcium level was elevated in eight cases. The serum parathormone value was determined in 13 cases, it was elevated in all cases. Less than 500 mg tissue was removed in 12, between 500 and 6000 mg in 19 and over 6000 mg in 3 cases. Nodular hyperplasia was demonstrated in 11 and diffuse hyperplasia in 23 patients. The serum calcium and parathormone levels fell markedly after the operation, and pruritus, bone pains and mental disturbances were markedly alleviated. Complete recovery was achieved only by a successful renal transplantation, but the operation had often a favourable effect on the grave symptoms.


Secondary hyperparathyroidism and its sequelae in renal transplant recipients. Long term findings in a series of conservatively managed patients.

The prevalence and duration of secondary hyperparathyroidism in 42 renal transplant recipients, and the sequelae of this condition, were studied. Immediately before transplantation, an elevated PTH-value was recorded in 76% of the patients, postoperatively there was a marked drop. Early after successful transplantation, 57% of the patients had hypercalcemia. At follow-up 3 years later, moderate hypercalcemia persisted in half of the patients but only 3 patients had significantly elevated PTH. The quality of renal graft function was not inferior in the hypercalcemic patients. Subperiosteal bone resorption and soft tissue calcifications were more common among the hypercalcemic patients. Our data suggest that secondary hyperparathyroidism can be managed conservatively in most renal transplant recipients. If progressive bone changes occur, surgical removal of parathyroid tissue should be considered.


The role of parathyroidectomy in the treatment of secondary hyperparathyroidism before and after renal transplantation.

In a series of 335 renal transplant recipients, 28 patients underwent parathyroidectomy due to secondary hyperparathyroidism. Twenty patients were operated on prior to renal transplantation, 8 subsequent to it. Solitary adenomas were found in 6 cases, diffuse hyperplasia in 22. Fifteen of the patients with diffuse hyperplasia underwent total parathyroidectomy with autotransplantation of parathyroid fragments into the sternocleidomastoid muscle, subtotal parathyroidectomy was performed in 7. Four hypercalcaemic patients underwent parathyroid surgery because of deteriorating transplant function but without improvement. Following parathyroidectomy, 21 patients became hypocalcaemic. 15 of these patients had undergone total parathyroidectomy and autotransplantation. Dihydrotachysterol substitution was accompanied by toxic symptoms in three patients on dialysis and by deteriorating renal function in two transplanted patients. Therefore, subtotal parathyroidectomy is recommended as the surgical procedure of choice in the treatment of secondary hyperparathyroidism before, as well as after renal transplantation.


Explorative parathyroidectomy before and after kidney transplantation.

Twentytwo parathyroidectomies were performed in a series of about 200 patients. Surgical exploration was performed in less than 5% of patients with slowly progressive uremia, and of patients on maintenance haemodialysis, whereas as many as 15% of patients returning to dialysis after graft failure were operated on. After successful transplantation appoximately 10% of a patients with an initially functioning graft ultimately had a neck exploration. On three occasions this parathyroidectomy was acutely performed. In about one third of the surgically explored cases the parathyroid glands displayed marked assymetry and/or histological features possibly indicative of adenoma formation or "autonomous nodules". The incidence of surgical complications was low and beneficial clinical effect were often encountered. It thus seems possible to defend a liberal attitude towards the performance of parathyroidectomy in patients accepted into a transplantation programme.


Renal function in hypercalcemia after renal transplantation.

A case of transient hypercalcemia in a 53-year-old female, who received a necro-kidney transplant, has been examined. The hypercalcemia was caused by vitamin D intoxication on three separate occasions. Each period of even moderate hypercalcemia produced a rapid fall in renal function. The effect was reversible. These findings are discussed in the light of earlier reports on stable renal function in post-transplant hypercalcemia.


The influence of 13 clinical and immunological factors on renal graft survival: a contingency table analysis.

A statistical method which accounts for the heterogeneity of clinical materials is presented and applied to a material of necrokidney transplantations. It is concluded that the recipient sex and the period in which the transplantation was performed are the most important factors (best prognosis for female recipients, best programs for transplantations in the first periods) and that the HLA-match grade has a significant influence on graft survival for male recipients and transplantations with short cold ischemia time. The present analysis has furthermore demonstrate the heterogeneity of the material as judged by the associations between factors and the overestimation of the influence of some of the factors by direct comparisons.


Delayed renal and extrarenal complications following primarily successful renal transplantation.

Delayed renal and extrarenal complications after primarily completely successful renal transplantations is surveyed. All cases in which a surgical or clinical complication, a rejection or a complication of the immunosuppressive treatment had occurred were omitted. Primarily, 84 out of 476 transplantations (17%) were completely successful. After six months, the continued course was entirely uneventful in 47 of these cases. In 37 some kind of renal and/or extrarenal complication occurred 6-114 months after the primarily successful course. The complications could not be correlated to histocompatibility, sex, age or basic disease. During the last years, when the basic immunosuppressive treatment was reduced and principally alternative day treatment of corticosteroids was used, the complications diminished.


Late complications after successful renal transplantation.

Of the patients treated with renal transplantation in Gothenburg between 1965 and 1972, 128 (38%) eventually had a "successful" transplant, i.e. a well-functioning graft (primary or secondary) beyond the third year after transplantation. The actuarial ten-year survival was 75%, 95% of these patients were well rehabilitated, medically and socially. Slow chronic rejection of the graft was the most common late complication and was responsible for an annual rate of graft loss of about five per cent. Avoiding overtreatment with immunosuppressive drugs, this complication should be met by early retransplantation. Ten out of 17 deaths occurred despite continued good graft function, seven of these being due to arteriosclerotic disease. In patients with continued good transplant function, negative effects of chronic immunosuppression were relatively uncommon: infection and malignancy caused the death of one and two patients, respectively. The only infectious disease seen in increased frequency was Herpes Zoster. This pattern of late complications with a high incidence of arteriosclerotic disease and a low incidence of infectious complications in the late transplantation course is not in accordance with other reports, where the reverse situation has prevailed. This difference might partly be explained by high age of the patients and adherence to a low-dose policy for chronic immunosuppression in our programme.


Arterial stenosis in renal transplantation.

Stenosis of the renal artery of the transplant (RAT), is reported with a frequency of 5-10% (Nerstrøm, Ladefoged & Lund 1972, Nilsson, Henriksson & Thoren 1976, Beachley, Pierce, Boykin & Lee 1976). The stenosis is significant if it deteriorates the renal function or elevates the arterial blood pressure. The angiographic impression of a stenosis depends on the projection and it is difficult to correlate the radiological findings with the blood flow. Moreover both renal failure and hypertension might depend on other factors than stenosis of the RAT. The aim of this study was to establish how often a reconstruction of a RAT suspected of being stenotic would benefit the patient.


Cancer as a late-onset complication of kidney transplantation.

A Scandinavian material of 2,683 transplanted patients, 59 of whom were diagnosed to have tumours, was analysed and the following found: 1) a greatly increased incidence of mesenchymal tumours (especially reticulosarcomata), 2) a greatly increased occurrence of "chronic pyelonephritis" (as a primary disease) among tumour patients, and 3) a correlation between tumour incidence and HLA-B mismatch between donor and recipient. Based on this material it is proposed that chronic immunostimulation in the recipient caused by graft antigens and bacteria and virus antigens puts a stop to T-suppressor lymphocyte function and subsequent proliferation of the lymphoid tissue, and that this is a major factor in the appearance of tumours derived from mesenchymal tissue, whereas the occurrence of ectodermal tumours is a result of a series of other oncogenetic factors.


Arterial disease with ischemic ulcerations in renal transplanted recipients.

Four cases of wide-spread arterial calcifications and peripheral necroses developing after successful renal transplantation are presented. In two cases parathyroidectomy was performed to prevent progress of the peripheral ischemic ulcers. In one of these cases, this was followed by healing of the necroses. In the two other cases parathyroidectomy had been performed because of hypercalcemia in the post-transplantation period. Ischemic ulcers appeared in these patients during treatment with vitamin D and healed after withdrawal of this therapy. Prevention of uremic arterial disease might be obtained by early control of serum phosphate levels and by renal transplantation at an early stage of renal disease. Parathyroidectomy should be considered in the treatment of developing peripheral gangrene in uremic patients and renal transplant recipients. Also, there are obvious hazards connected with vitamin D therapy in these patients.


Steroid diabetes after renal transplantation--a preliminary report.

The incidence of steroid diabetes mellitus was studied retrospectively in 84 renal transplant recipients with grafts which had functioned longer than 3 months. The observation time ranged between 3 and 36 months (mean 17 months). Overt diabetes necessitating treatment was found in 24 patients (29%). Another 14 patients had transient elevations in blood glucose. The incidence of steroid diabetes was found to correlate with increasing age and body weight and with the number of rejection episodes. In the majority of the patients with manifest diabetes it was diagnosed within three months after transplantation.


Ocular complications in recipients of kidney transplants.

104 renal transplant recipients have been examined regarding ocular complications. A high incidence of posterior subcapsular cataracts has been found, increasing with time after operation. Only 2 cases of open angle glaucoma were found, indicating a seemingly small risk for developing a corticosteroid-induced glaucoma in such patients. A high frequency of treatment-resistant herpes simplex keratitis, probably due to reduced corneal resistance, was found.


Permanent withdrawal of prednisone in nekro-kidney transplantation.

Starting 2.5 (2.0-3.9) years after grafting prednisone (but not azathioprine) has been gradually reduced below the conventional maintenance dose of 10 mg per day in 43 and has up until now eventually been completely withdrawn in 23 out of 47 consecutive patients with a first nekro-kidney transplant, which was well functioning at 2 years after transplantation. There appeared to be an increased risk of rejection during reduction of prednisone from 10 to 2.5 mg per day, but 20 out of the 23 patients in whom prednisolone has by noe been completely withdrawn have maintained stable and normal graft function over an average period of 1.6 (0.1-3.0) years on zero prednisone.


Rena transplantation and HLA-A, B matching. Theoretical considerations concerning pool size.

The rate of improvement in HLA-matching quality with increasing pool size is predicted. The frequency of HLA-A, B compatible matches increases rapidly up to approximately 47% for pool size 1000 and from then on the increase is more moderate while for HLA-A, B fullhouse-identical matches the increase in frequency is slower and more constant, the expected frequency being approximately 33% at a pool size of 2500. The import/export balance between two cooperating pools is estimated for various relative pool sizes and transplantation activities.


Experimental and clinical experiences with long-term kidney preservation by use of simpel hypothermia.

In an experimental work published in 1973, it was found, that it was possible to preserve pig kidneys with up to one hour of warm ischemia for 24 hours using pretreatment with chlorpromazine and subsequent preservation with simpel hypothermia (Collings C2-solution). Clinical experiences with this method are now presented and confirm, that this method allows preservation of ischaemic damaged kidneys for about 24 hours.


Kidney preservation with Collins' and Sachs' solution.

We suggest that the flush-out and short-term-storage solution (Brunius-Gelin) solution so far used in Scandinavia prior to continuous hypothermic perfusion, be replaced by Collins' C2 solution or Sachs' II solution. The question of which one of these should be preferred will need further elucidation. The advantages to be obtained by this change are several: increased simplicity and increased uniformity within our organ exchange organizations as well as the possibility of prolonging non-perfusion preservation periods, with savings in manpower and costs, and increasing simplicity and safety during organ transportation.


HLA-ABC matching and outcome of primary cadaveric kidney transplantations in Gothenburg.

The influence of HLA matching was studied in 319 informative cases of primary cadaveric kidney transplantations performed in Gothenburg 1969--1976. Foreign HLA-B antigens seemed to be of more importance for graft survival than foreign HLA-A or -C antigens. The prognosis for graft survival was significantly improved for match-grades with one foreign HLA-B antigen from the period 1973--1976 compared to those from the period 1969--1972. Match-grades with two foreign HLA-B antigens had significantly reduced graft survival during the period 1973--1976.


The influence of HLA-A, -B, -C, and -D matching on kidney graft survival.

The influence of HLA matching has been studied in a Norwegian material of 147 living related first transplants, 281 cadaveric first transplants and 48 cadaveric second transplants. Graft survival corresponded closely to HLA antigen disparity and degree of MLC response in combinations transplanted with kidneys from living related donors. In patients transplanted with cadaveric grafts. HLA identical and compatible grafts performed significantly better than imcompatible grafts. Matching for HLA-C in addition to HLA-A and -B did not seem to improve graft survival.


The significance of HLA-A and -B matching for cadaver-kidney survival in Stockholm 1970--1976.

The significance of HLA-matching for the survival of cadaver kidneys, transplanted between January 1970 and June 1976 to 170 uraemic patients has been assessed. When the patients were divided into groups according to degree of HLA compatibility it was found that the groups so obtained were comparable neither with regard to the quality of the transplants nor to the immunosuppressive therapy given. This was due to multiple changes in policy in 1973. When the case material was divided into patients treated before and after 1973, comparable groups were obtained within each series. The only correlation found was that, in the chronologically later groups, 2 year survival rate of transplants with E-G match (3--4 incompatibilities) was inferior to that of transplants with C-D match (1-2 incompatibilities).


HLA determination in renal transplantation with living donor.

During the period Feb. 1967--Aug. 1976 94 first renal transplantations were performed using living related donors and histocompatibility tests. Eight transplantations were performed on children under 15 years old and four on patients over 50 years old. The rest of the patients were between 15 and 50 years old. No exclusions were performed. 22 patients expired, seven of these with a well functioning graft. The patient survival (P.S.) was 90% at 1 year, 87% at 2 years and 77% at 5 years, the graft survival (G.S.) was 81% at 1 year, 80% at 2 years and 68% at 5 years. The clinical results showed a fairly good correlation with the histocompatibility degree. In the A-B-match groups the 1, 2 resp. 5 years P.S. was 95, 96 resp. 89% and G.S. 90, 90 resp. 89%. In 43% of the patients rejection of variable degree developed. The rejection led to graft loss in 12%.


Corneatransplantation and matching for HLA-A and B.

Analysis of 140 corneatransplantations performed without selection showed a significant correlation between the HLA-A and B match and the clinical outcome. Furthermore, a highly significant correlation was found between rejection episodes and a positive direct cell-mediated lympholysis.


Patterns of immunological anti-donor reactivity in renal allotransplanted patients--a prospective study.

The immunological reactivity of 20 consecutive renal allotransplanted patients against donor lymphocytes were followed from the day of transplantation and subsequently twice weekly until dismissal or graftectomy. The investigations concerned Complement Dependent Cytotoxic (CDC) antibodies, Antibody Dependent Cell-Mediated Cytotoxicity (ADCC) and Cell-Mediated Lymphocytotoxicity (CML). Five patterns of immunological reactivity were observed parallelling the clinical courses. A specifically positive CML test was highly but not absolutely correlated to clinical graftrejection. Graftrejection was in general not preceeded by positive CML. The patterns of CDC and ADCC reactivity in relation to graftrejection were not evident.


The use of tests for cell mediated cytotoxicity in clinical kidney transplantation.

The test systems for antibody-dependent cell-mediated cytotoxicity (ADCC) and direct cell-mediated lympholysis (DCML) were used to measure the immunological response of kidney transplanted patients against donor related targets before and after transplantation and in long term allograft recipients. An isolated positive ADCC cross march was found to indicate a grave graft prognosis. Positive DCML reactions were correlated to clinical rejection. In long term recipients antibodies reactive in ADCC against donor related targets seemed to be correlated with a state of chronic rejection.


The effect of blood transfusions on cadaver kidney transplants--an analysis of patients transplanted in Uppsala.

The kidney graft survival in 117 transplanted patients was investigated with reference to blood transfusions. No improvement of graft survival was observed in the transfused patients as compared to the patients who were not transfused or had got autologous blood only.


The effect of blood-transfusions on renal allograft survival.

The relation between previous bloodtransfusions and renal allograft survival was studied retrospectively in 88 patients, who had been transplanted for the first time. The allograft survival rate was higher in the group who had received bloodtransfusion than in the group who had not. This difference was significantly greater when considering patients who had not previously been pregnant, e.g. patients without previous stimulation of the immuno system. The material shows no difference in allograft survival between previously transfused and non transfused patients, when considering age, sex or disease of kidney. In this retrospective study it is concluded that previous transfusions improved the prognosis of the transplantation. A prospective study has yet to be done, in order to enlighten the influence of various other factors on the allograft survival rate such as length of period or uraemia and of dialysis.


Influence of blood transfusions on kidney transplant and uremic patient survival.

The influence of blood transfusions on kidney graft survival in 167 first cadaveric transplants and 85 first living related transplants is presented. Blood transfusions had no effect upon kidney graft survival in the patients transplanted with kidneys from living related donors. A significantly better graft survival was observed in the transfused group of patients transplanted with cadaveric kidneys. This beneficial effect was most pronounced in men. When patient survival was analyzed, however, a possible beneficial effect of blood transfusions was almost nulled out when patients dying while waiting for a transplant were included. The majority of these latter patients had been transfused and many had formed HLA antibodies.


Transfusion and kidney graft survival in Finland.

The influence of blood transfusions prior to kidney transplantation on graft survival was analyzed in a series of 406 first transplantations, including 321 necro-kidneys. Among the 131 females with necrokidneys, 14 had not been pregnant or received transfusions, neither had 70 of the 190 male necrokidney recipients been transfused. In comparison with these controls, a slightly better graft survival was observed in the "immune-triggered" patients, especially in those with no detectable lymphocytotoxic antibodies before transplantation, and more markedly in female than in male patients. The effect of pregnancies seemed the same as that of transfusions. The age and pretransplantation dialysis treatment of the recipient appeared irrelevant to graft survival. "Immune-triggering" slightly improved graft survival also in the living donor category.


Blood transfusion and kidney transplantation.

During the years 1968--1976, 115 nondiabetic primary cadaveric transplantations were performed in southern Sweden. For 95 of these patients there was an observation period of at least one year. 32% of these patients had never received a blood transfusion. These recipients had an lower one year graft survival (33%) than those who had received one or more transfusions (48%). Patients who had received more than five transfusions did not show a higher graft survival than other transfused kidney recipients. Presence of cytotoxic antibodies also decreased the one year graft survival both in the transfused and not transfused patient groups.


Blood transfusion and primary graft survival in male recipients.

The outcome of primary kidney transplantation in 241 male patients was studied with reference to pretransplant blood transfusions. 55 patients received kidneys from living related donors with one shared HLA-haplotype, 186 patients received kidneys from cadaveric donors. The graft survival was calculated after exclusion of graft loss due to non-immunological reasons. The graft survival was found to be significantly higher in transfused recipients, especially in patients receiving kidneys from living related donors.


A controlled trial of antihuman lymphocyte globulin (Behring) in cadaveric renal transplantation: improvement in graft and patient survival at one year using a high-dose regimen.

A controlled study of the effect of antihuman lymphocyte globulin (AHLG) on patient and kidney transplant survival has been performed. The AHLG was administered as an adjuvant to the routine immunosuppressive drugs in either high (30 mg/kg) or low (15 mg/kg) doses, control patients received no AHLG. The clinical condition of the recipients and the quality and the degree of immunological compatibility of the transplants were comparable. During the period of the study, the results of all first-time cadaver-kidney transplantations to non-diabetic uraemic patients were included. The actuarial graft survival rates at 12 months for the three groups (high dose, low dose and control) were 67%, 49% and 35%. The corresponding patient survival rates were 91%, 66% and 65% respectively. The difference between the results in the high dose AHLG and in the control group was significant (p less than 0.05).


The effects of anti-lymphocyte globulin on lymphocyte subpopulations in recipients of kidney allografts.

During the first three weeks following transplantation kidney allograft recipients were treated with zero, 15 or 30 mg/day of anti-human-lymphocyte globulin (ALHG, Behringwerke). T-cells were determined as sheep erythrocyte rosette forming cells (E--RFC) and B cells were identified using the surface membrane immunoglobulin (SmIg) marker. The proportion of E--RFC decreased with increasing AHLG dose. The absolute number of E--RFC was lower in patients receiving 30 mg/kg AHLG compared to those not treated with AHLG. In patients receiving 30 mg/kg AHLG the mean number of lymphocytes covered with AHLG was 78 +/- 3%, detected by using a fluorescent anti-horse IG; significantly higher (p less than 0,001) than 31 +/- 3% in patients treated with 15 mg/kg AHLG. T cell function was measured as the mitogenic response to phytohemagglutinin (PHA) and Concanavalin A (Con A) and the B cell response was measured as the mitogenic response to anti-B2microglobulin (anti-B2m). No differences in response to Con A or anti-B2m were seen in lymphocytes from the various groups of patients. The response to PHA increased (p less than 0,05) in patients treated with the highest dose of AHLG.


Clinical experience with antilymphocyte-globulin in cadaveric kidney transplantation.

Two different commercially available anti-lymphocyte-globulin preparations have been used in 30 recipients of primary cadaveric kidneys. No difference in graft survival was found within three years after transplantation compared to 102 primary cadaceric kidney recipients who only received basic immunosuppression. When only patients completing an intended ALG dosage were considered, the one-year graft survival was 65% compared to 52% in patients not receiving ALG. In this series of ALG treated patients no major benefits were found compared to the basic immunosuppressive regimen used at this transplantation centre.


Antilymphocyte globulin in cadaveric renal transplantation--a controlled trial.

In a prospective, controlled study, 40 patients receiving a cadaveric renal transplant (first grafts) were randomized into two groups. Twenty patients were given antilymphocyte globulin (Behringwerke AHLG) in a dose of 10 mg/kg body weight for a total no. of 25 times in combination with a standard regimen of prednisone and azathioprine. Graft survival and graft function were similar in the two groups both at 18 and 30 months post transplantation. No serious side effects of the ALG treatment were observed.


Treatment of acute gouty arthritis with proquazone and indomethacin. A comparative, double-blind trial.

Eighteen patients (11 men and 7 women) suffering from primary or secondary gout, were treated with either proquazone or indomethacin for acute attacks in a double-blind study. There were 9 patients in each treatment group. A marked improvement of clinical symptoms appeared in 2-3 days. In the proquazone group, complete remission was achieved in 6 patients, a good result in one, and a slight improvement in one patient, whereas one patient did not respond to treatment. The corresponding figures for the indomethacin group were 4 cases with complete remission, 4 with a good result, and one not responding to treatment. A significant decrease in s-uric acid values was noted in the proquazone group. In this group too, mild gastrointestinal symptoms appeared in 2 patients.


A new anti-inflammatory drug, proquazone, and ibuprofen in the treatment of degenerative joint disease of the knee (gonarthrosis). A double-blind comparative study.

The therapeutic effect and the tolerance of a new non-steriod anti-inflammatory compound, proquazone, were compared with those of ibuprofen in a double-blind, randomized study on patients with gonarthrosis. Totally 39 patients participated in the study: 19 patients in the proquazone group and 20 patients in the ibuprofen group. The two drugs were given in daily doses of 900 mg and 1200 mg respectively during 3 weeks. In both treatment groups a good result was achieved in more than 70% of the cases, but proquazone seemed to be more effective in reducing swelling and pain of knee. There were more side effects in the proquazone group than in the ibuprofen group, but they were generally mild and disappeared spontaneously. Only one patient in the proquazone group withdrew, because of epigastric discomfort.


A long-term comparison of proquazone and naproxen in the treatment of osteoarthritis of the hip.

The efficacy and tolerance of 900 mg/day proquazone were compared with those of 500 mg/day naproxen in a three-month trial with 40 patients suffering from osteoarthritis of the hip. Proquazone was found to be more effective than naproxen in providing relief of symptoms and improving the patient's condition. The side effects of proquazone were exclusively gastrointestinal but occurred more frequently than with naproxen. With one exception, none of the symptoms were serious enough to require suspension of therapy. These results suggest that the action of proquazone provides a good balance between clinical efficacy and tolerance.


A long-term double-blind comparative study on proquazone (Biarison) and ibuprofen in rheumatoid arthritis.

The efficacy and tolerance of proquazone, 900 mg, and ibuprofen, 1200 mg, were compared in a randomized, double-blind clinical trial of 6 months' duration, with 44 patients, 21 on proquazone and 23 on ibuprofen. Comparison of proquazone-treated patients with patients treated with iburofen showed a significantly better improvement , as is demonstrated by the significant differences in the Lansbury Index, in nocturnal pain, final assessment of therapeutic effect, and number of interruptions due to lack of efficacy. All differences were in favour of proquazone, proving its therapeutic superiority over ibuprofen. The side effects in the proquazone group were mainly gastrointestinal, and 2 patients broke off treatment prematurely due to diarrhoea (in one patient, lack of efficacy was a contributory cause). A third patient discontinued because of moderate nausea and dizziness. In the ibuprofen group, 4 patients discontinued because of side effects (skin eruptions, dizziness, epigastric discomfort, and one thrombocytopenia) in addition to lack of efficacy. Proquazone seems to be an effective and well tolerated anti-inflammatory analgesic.


A comparative, double-blind trial with proquazone and naproxen in the treatment of rheumatoid arthritis.

In a double-blind trial lasting 6 months, 36 patients with classical or definity rheumatoid arthritis were divided into two groups, one receiving 3x300 mg proquazone/day and the other 2x250 mg naproxen plus one placebo capsule/day. Efficacy parameters were assessed and laboratory tests performed at regular intervals throughout the trial. Both drugs were well tolerated, in that no abnormal changes were found in the results of laboratory tests in either group, and that drug-related side effects, mainly gastrointestinal disturbances, occurred in just over half the cases in each group. Both drugs improved the Lansbury Index, especially grip strength, walking time, and ESR. Proquazone did significantly better than naproxen in improving ESR and nocturnal pain. More therpaeutic successes were recorded with proquazone than with naproxen in the overall assessment at the end of the trial.


Proquazone (Biarison) and indomethacin (Indocid) in the treatment of ankylosing spondylitis. Two comparative, clinical, double-blind studies.

The effect and tolerance of proquazone and indomethacin in patients suffering from ankylosing spondylitis were compared in two separate 3-week clinical, double-blind, randomized studies on total of 60 patients. In the first study 16 patients were treated with proquazone and 14 patients with indomethacin, and in the second study 15 patients were treated in each group. Both drugs were found to have an evident, equally strong effect on pain and functional capacity in daily doses of 900 mg and 75mg respectively. Severe side effects were not noted with either one of the drugs. Patients with previously known intolerance to indomethacin were excluded from the studies. Gastronitestinal disturbances seem to be the most commonly appearing side effect in patients treated with proquazone.


2 (1H)-quinazolinones as novel non-acidic anti-inflammatory agents.

Chemical modification of 1-methyl-4-phenyl-2 (1H)-quinazolinone, a new lead in the area of non-steroidal anti-inflammatory agents, has led to 1-isopropyl-4-phenyl-7-methyl-2 (1H)-quinazolinone, proquazone. The overall anti-inflammatory profile of proquazone compares well with indomethacin qualitatively and quantitatively. It is particularly noteworthy that proquazone is the first potent anti-inflammatory drug of a non-acidic nature.


A clinical trial of the analgesic properties of Voltaren (diclofenac sodium).

In a double-blind comparison with placebo in 60 patients suffering from post-operative pain following the surgical removal of a third molar in the lower jaw, statistical analyses showed that Voltaren (diclofenac sodium) in a single dose of 50 mg had a significantly greater analgesic effect than placebo. The technique to be used for studies with analgesic drugs is briefly discussed.


A study of the anti-inflammatory effect of Voltaren in patients with rheumatoid arthritis.

In a double-blind, crossover study conducted in ten hospitalised patients suffering from active rheumatoid arthritis, the anti-inflammatory effect of diclofenac sodium (Voltaren) in a daily dosage of 125 mg was compared with that of placebo under strictly standardised conditions. Changes in reversible articular swelling were determined by measuring the circumference of involved wrist, knee, metacarpophalangeal, interphalangeal, and metatarosphalangeal joints. A consistent decrease in joint swelling occurred in response to treatment with diclofenac sodium, as compared with a consistent increase following placebo medication. This difference was significant at the 5% level for all except the interphalangeal joints. Similarly, in response to diclofenac sodium a greater improvement was noted in duration of morning stiffness and grip strength and a greater reduction in the total number of painful and swollen joints. The status of the rheumatoid condition improved in nine patients following treatment with diclofenac sodium, but in none following placebo medication. Two patients reported unwanted effects, consisting of a sensation of fullness during treatment with diclofenac sodium in one case and of heartburn during both treatment periods in the other. No laboratory abnormalities were noted.


Diclofenac sodium (Voltaren) and indomethacin in the ambulatory treatment of rheumatoid arthritis: a double-blind multicentre study.

In a double-blind crossover trial conducted on a multicentre basis, 109 patients with "classic" or "definite" rheumatoid arthritis were treated for two weeks with diclofenac sodium (Voltaren, 25 mg t.i.d.) and indomethacin (25 mg t.i.d). Both drugs led to a clear-cut decrease in morning stiffness, as well as to a significant improvement in pain at rest and on movement. In these respects no significant difference between the two-drugs was observed. As regards their effect on status of rheumatoid condition, however, a trend towards a significant improvement was discernible, in the investigator's opinion, only in response to diclofenac sodium. "Unwanted effects" were mentioned by 25 patients before the trial, by 31 during treatment with diclofenac sodium, and by 33 during treatment with indomethacin. While the patients were receiving indomethacin, five of them discontinued treatment on account of side effects (headache in three cases, headache and tiredness in one case, and an allergic skin reaction in one case) and one of them, who complained of headache, lowered the dosage; treatment with diclofenac sodium was discontinued because of side effects by only one patient, who had developed an allergic skin reaction.


Diclofenac sodium (Voltaren) and naproxen in the treatment of rheumatoid arthritis: a comparative double-blind study.

In a double-blind, between-patient trial the efficacy and tolerability of two new non-steroid anti-inflammatory analgesics-diclofenac sodium (Voltaren) 50 mg b.i.d. and naproxen 250 mg b.i.d.-were compared in hospitalised patients with rheumatoid arthritis. Both drugs had a clearly positive effect on the duration of morning stiffness, bilateral grip strength, pain at rest, and pain on movement. No statistically significant difference between the two drugs was found with respect to clinical efficacy. Three patients treated with diclofenac sodium reported unwanted effects, as compared with seven patients receiving naproxen. These unwated effects led to premature discontinuation of the treatment in one patient on naproxen. Thus, although both drugs were well tolerated, it appeared that diclofenac sodium caused somewhat fewer unwanted effects.


A comparative short-term trial with Voltaren (diclofenac sodium) and naproxen in soft-tissue rheumatism.

In a double-blind study, diclofenac sodium (Voltaren)--administered for 14 days in a dosage of 25 mg t.i.d.--was compared with naproxen (250 mg b.i.d. for 14 days) in the treatment of 120 patients with soft-tissue rheumatism. Assessment of the efficacy of the two treatments was based upon changes, recorded once a week, in the following parameters: pain at rest and on movement, swelling, local tenderness, functional impairment, limitation of movement, and sleep disturbances. The incidence of unwanted effects was also recorded, and the effects themselves were classified according to the probability of their being causally related to the trial preparations. Both drugs appeared to be effective in relieving symptoms associated with soft-tissue rheumatism. In most indications the therapeutic efficacy of the two preparations was similar. In patients suffering from diseases affecting the shoulder region, however, diclofenac sodium was significantly more effective. Unwanted effects rarely occurred with either drug.


The long-term efficacy and tolerability of Voltaren (diclofenac sodium) and indomethacin in rheumatoid arthritis.

A report is given on a long-term controlled trial in which diclofenac sodium (Voltaren) was compared with indomethacin in 36 patients with rheumatoid arthritis, both drugs being administered in a dosage of 75-125 mg daily. In this trial, planned as a double-blind study, each patient was to participate for six months, after which the patients treated with diclofenac sodium were to be followed up for a further six months. By the end of the first six months, diclofenac sodium had proved to be clearly superior to indomethacin in terms of therapeutic efficacy. Moreover, unwanted effects referable to either the central nervous system or the gastro-intestinal tract were less common and less severe in the patient treated with diclofenac sodium than in those receiving indomethacin. These results demonstrate that, when given as long-term treatment to patients suffering from rheumatoid arthritis, Voltaren is both effective and well tolerated.


The effect of inhaled RS 7540, a xanthone, on exercise-induced asthma.

The effect of 71 oxo-7-thiomethoxyxanthone-2-carboxylic acid sodium salt (RS 7540) in inhibiting exercise-induced asthma was compared with that of placebo in a double-blind crossover study. Single doses of 40 mg were given by inhalation to 12 patients. Ten of these subsequently received a dose of 20 mg. RS 7540 at both dose levels had a statistically significant effect in giving total or partial protection from exercise-induced bronchospasm; however, no dose relationship was apparent.


The pleiotropic effect of spontaneous single-step variant production in Mycobacterium intracellulare.

A strain of M. intracellulare, AT 13786, derived from human sputum, gave rise to transparent and opaque colony forms which were cloned and investigated. From the results the conclusion was drawn that the opaque form was a mutant of the transparent type and possessed alterations in the cell envelope which were responsible for enhanced permeability. The opaque form was more susceptible to a number of antibiotics; it grew faster in standard medium, and was not dependent on tween for dextrose utilization. Tween enhanced the antibiotic susceptibility of the opaque form more than that of the transparent. The avirulent opaque colony form of the pathogenic strain serotype Boone also revealed a loss of tween dependence for dextrose utilization. The significance of the overall change has been discussed with respect to the question of virulence.


Hexoprenaline and terbutaline administered by inhalation. A comparison between two beta2-adrenoreceptor agonists with respect to effect on bronchial obstruction, heart rate, blood pressure and muscle tremor.

In a controlled double-blind cross-over study in 15 patients with reversible bronchial obstruction hexoprenaline (Ipradol, 0.20 mg/puff) and terbutaline (Bricanyl, 0.25 mg/puff) when administered as metered aerosol in a dosage of one puff followed by two puffs 30 min later produced the same maximum improvement of ventilatory function. However, after inhalation of terbutaline a more sustained broncholytic effect was obtained than after hexoprenaline. Similar results were obtained in six patients after doubling the dose of each agent. The influence on pulse rate and blood pressure was negligible with either agent. The amplitude of finger tremor was measured after 2 + 4 puffs. No significant changes in mean values occurred after either of the two agents although after hexoprenaline an increase in amplitude of more than 100% was recorded in two out of six patients 30 min after the second dose.


Bovine tuberculosis in man--reinfection or endogenous exacerbation.

Cattle tuberculosis was totally eradicated in Sweden 20 years ago. Twelve cases of bovine tuberculosis in man were reported in 1974 and 1975. All cases lived for many years in areas where cattle tuberculosis had previously been common. No recent source of infection could be demonstrated. These findings are in accordance with an exacerbation of a distant infection.


Benzene--attempts to establish a lower exposure standard in the United States. A review.

Production usage and potential occupational exposure to benzene are described in this review, as are selected, relevant reports presenting evidence evidence implicating benzene as a causative factor in leukemia, particularly acute myelogenous leukemia, pancytopenia (including aplastic anemia) and chromosomal aberrations. A chronologic account of events in the 1970s in the United States, largely based on epidemiologic evdince collected and prepared by the National Institute for Occupational Safety and Health, caused the regulatory agency, the Department of Labor, through its Occupational Safety and Health Administration to declare benzene a human leukemogen and carcinogen and to publish an emergency temporary standard of 1 ppm in May, 1977, but this standard has not been legalized.


Synthetic maps of human gene frequencies in Europeans.

Multivarate techniques can be used to condense the information for a large number of loci and alleles into one or a few synthetic variables. The geographic distribution of synthetic variables can be plotted by the same technique used in mapping the gene frequency of a single allele. Synthetic maps were constructed for Europe and the Near East, with the use of principal components to condense the information of 38 independent alleles from ten loci. The first principal component summarizes close to 30% of the total information and shows gradients. Maps thus constructed show clines in remarkable agreement with those expected on the basis of the spread of early farming in Europe, thus supporting the hypothesis that this spread was a demic spread rather than a cultural diffusion of farming technology.


Age determination of an Alaskan mummy: morphological and biochemical correlation.

Aspartic acid racemization analysis of a tooth from an Alaskan mummy yielded an age at death of 53 (+/- 5) years, which correlates well with earlier estimates based on morphological features. This study illustrates the value of integrative approaches to paleopathologic problems and the importance of preserving rare specimens for the application of new techniques.


Unusual antibody-induced modulation of surface antigens in the cell coat of a bloodstream trypanosome.

Unlike other eukaryotic cells, Trypanosoma lewisi forms caps at 0 degrees C when incubated with rabbit immunoglobulin G(IgG) directed against surface IgG from the rat host. The host IgG, which is specific for parasite antigens, probably does not cause capping of these antigens in vivo, since trypanosomes treated with Fab fragments directed against rat IgG are uniformly labeled and do not cap at 0 degrees C or 37 degrees C.


Bone marrow origin of hepatic macrophages (Kupffer cells) in humans.

Hepatic macrophages (Kupffer cells) from two male recipients of bone marrow transplants from females were studied for fluorescent Y body staining and sex chromatin (Barr body). After the transplant, macrophages had the sex karyotype of the donor, indicating that human hepatic macrophages originate in bone marrow.


Antitrypanosomal effect of allopurinol: conversion in vivo to aminopyrazolopyrimidine nucleotides by Trypanosoma curzi.

The parasite Trypanosoma cruzi metabolizes allopurinol by a sequential conversion to allopurinol mononucleotide and aminopurinol mononucleotide. The latter is incorporated into RNA. This transformation of a widely used innocuous agent, allopurinol, into a toxic adenine analog appears to account for the antiprotozoan effect of allopurinol. These unique enzymatic activities appear to occur only in T. cruzi and the pathogenic lesihaminae. Allopurinol may serve as a model for the synthesis of similar antiprotozoan agents.


Research involving human subjects.

This article reports a study of the activities and performance of institutional review boards to protect human research subjects. Researchers and institutional review board members were generally supportive of the review system, although substantial criticisms were also heard. Institutional review boards had some direct impact on half of the proposals reviewed by requiring either modification of or additional information about proposed research. The data, however, raise questions about the effectiveness of some review board actions, for example, with regard to informed consent. Some policy implications of the study are presented.


Localization of inorganic phosphate in the pancreatic B cell and its loss on glucose stimulation.

Perifusion experiments have shown that there is a discharge of inorganic phosphate into the medium when insulin secretion from isolated islets is stimulated by glucose. Histochemical and microprobe examination of resting pancreatic islets in the electron microscope shows a specific accumulation of inorganic phosphate adjacent to the plasmalemma and nucleolus of the B (beta) cells. This phossphate is lost from the cells during secretory stimulation of islets with high concentrations of glucose.


The logic of adjunctive therapy in surgical patients with resectable cancer.

The principles and rationale of using multiple modalities (surgery, chemotherapy, radiotherapy, and immunotherapy) to treat solid malignancies is reviewed. Animal models of human tumors have clearly demonstrated the superiority of combining local treatment (eg, surgery) with systemic treatment (eg, chemotherapy). Although the results of many trials of adjunctive therapy in man are still preliminary, they warrant the caustious generalization that multiple modality therapy will increasingly become more effective than surgery alone for most types of solid tumors. Although the strategy of employing adjunctive therapy is rational, it must be emphasized that the therapeutic efficacy of specific drugs or agents for particular patients or tumor types has not always been satisfactory. Clinical trials now in progress may demonstrate more effective regimens. In the meantime, physicians should be cautious about using adjunctive therapy as standard treatment until long-term benefits and safety have been demonstrated. Participation in clinical trials is encouraged to verify the validity and application of this therapeutic approach.


Sir John Harington, Thomas Crapper, and the flush toilet.

With the population explosion of the last century, major changes in sewage removal and sanitation were necessary. Two men offered important designs for the modern flush toilet. Sir John Harington was a poet in 16th Century England, while Thomas Crapper was a plumber and businessman in the same country 300 years later. Harington will be remembered for eloquent words about the toilet and Crapper may be assured even greater remembrance for selling toilets and being named Crapper.


Protein binding of drugs--the clinical significance.

Drug-protein binding is reviewed from a clinical and practical point of view. Commonly used drugs are discussed and the effects of disease, drug dosage and hypoalbuminaemia on drug-protein binding are reviewed. Doses of highly bound (greater than 80%) drugs in patients with hypoalbuminaemia, liver disease or renal failure should be regularly reviewed.


Trofosfamide in the treatment of patients with cancer. A pilot trial.

The efficacy of trofosfamide (Ixoten; Noristan), a derivative of cyclophosphamide, was investigated in 76 patients. Those with solid tumours were given 50 mg/kg in 6 divided doses in 48 hours; those with chronic lymphatic leukaemia were treated with 100 mg orally 3 times a day for up to 10 weeks. Side-effects of treatment included leucopenia, thrombocytopenia, a fall in the haemoglobin level, haematuria and occasional alopecia. Nausea was never severe, and occurred in only half of the patients on a high dose and in none of the patients on a low dose. A therapeutic effect was observed in patients with breast cancer, cancer of unknown origin and pancreatic cancer. Twenty-one of 24 patients with chronic lymphatic leukaemia (all of whom had aggressive disease) responded to treatment, and complete remission (including normal bone marrow), was achieved in 5 of these patients.


Piracetam in the management of spasticity in cerebral palsy.

This article is a preliminary report of a new indication for the drug piracetam (Nootropil; UCB). It was found that piracetam was useful for the control of spasticity in 8 out of 16 patients with cerebral palsy. Side-effects were minimal.


The Bain anaesthetic circuit.

The Bain co-axial circuit is a recent and versatile addition to the semiclosed anaesthetic breathing systems. The relationship between the patient's arterial carbon dioxide tension (PaCO2) and fresh gas flow during intermittent positive pressure ventilation (IPPV) using this circuit has been reassessed. A mean PaCO2 of 33,4 mmHg for 64 patients was recorded using a fresh gas flow of 100 ml/kg/min and a mean PaCO2 of 37,3 mmHg for 55 patients using a fresh gas flow off 70 ml/kg/min.


Bromodeoxyuridine tablet methodology for in vivo studies of DNA synthesis.

5-Bromodeoxyuridine (BrdU) tablets with different physical characteristics are useful in a wide variety of studies requiring detection of DNA replication in vivo. These tablets can effect a high substitution of BrdU in DNA, thereby permitting sister chromatid differentiation in chromosomes stained with 33258 Hoechst alone or in conjunction with Giemsa. Baseline and cyclophosphamide-induced in vivo sister chromatid exchange frequencies in mouse spleen, marrow, and thymus were measured and found to be significantly greater than those in spermatogonia. Sister chromatid exchange analysis was also extended to mouse liver and to Chinese hamster and Armenian hamster marrow cells. Sister chromatid differentiation was observed in Armenian hamster meiotic tissue, and evidence for interhomolog chromatid exchange obtained.


Use of latex particles for analysis of heterokaryon formation and cell fusion.

A simple method for the quick and accurate detection of cell fusion utilizing latex particles as cytoplasmic markers was developed and is reported here. The method is particularly useful for demonstrating human skin fibroblast heterokaryons. Ingestion of latex particles did not affect the growth of primary human and established BHK(21)/C(13) hamster fibroblasts. In addition, somatic cell hybridization between hypoxanthine phosphoribosyltransferase-deficient (HPRT-) and thymidine kinase-deficient (TK-) mutants of BHK(21)/C(13) was also unaffected by lates particle ingestion.


Preoperative assessment of the patient with breast cancer.

The clinical assessment of patients with Stages I and II breast cancer is outlined in Figure 1. A chest x-ray film and serum alkaline phosphatase are the only routine studies indicated. If the serum alkaline phosphatase is abnormal in the presence of otherwise normal liver function studies, a bone scan, liver scan, and CEA should be obtained. Areas of increased radioactivity on bone scan are always evaluated by additional radiographs and in some cases tomograms. The majority of focal areas of increased radioactivity will demonstrate radiographic evidence of benign bone lesions, predominantly degenerative joint disease. Only those focal areas of increased radioactivity that are normal on x-ray film or show radiographic evidence of metastases are considered to be positive for metastatic disease. The results of the liver scan are correlated with the level of CEA. Focal areas of decreased radioactivity associated with a CEA greater than 5 ng per ml are considered to be metastases. In the absence of elevation of the CEA, focal areas of increased radioactivity should be biopsied prior to any further considerations as to definitive therapy. The clinical assessment of patients with Stage III disease is outlined in Figure 2. Patients with this stage of disease have a much greater chance of having clinically occult metastases of sufficient size to be detected by chest x-ray film, serum alkaline phosphatase, and bone scan. If the serum alkaline phosphatase is abnormal, a liver scan and CEA are obtained in an effort to detect liver metastases. The same sequence of events is then followed as suggested for patients with Stages I and II disease. Several new techniques of detecting occult metastases are being evaluated. Biomarkers are the subject of another article in this volume. The use of computerized axial tomography is also being evaluated as a means of detecting lung, liver, and mediastinal metastases. The results of these initial clinical trials should be carefully followed.


Immunology, tumor markers, and breast cancer.

Although our knowledge of immunologic processes in breast cancer is still inadequate, many preliminary studies described here may yield valuable information after long-term patient follow-up. At present, there is no specific tumor marker diagnostic of breast cancer, but markers such as CEA, ferritin, immune complexes, and specially estrogen receptors have strong potential as prognostic indicators. As a group, breast cancer patients, as do those with other malignancies, demonstrate reduced immunologic capacity, therefore assays of nonspecific immune function may not be relevant. Assays of "specific" reactivity to breast tumor antigens, however, warrant further investigation as clinical tools. Application of immunotherapy to breast cancer is relatively recent and few trials have more than preliminary data. Determination of estrogen receptors should be included in future clinical immunotherapy protocols so that true evaluation of immunologic responses may benefit, hopefully, from our awareness of the endocrine milieu.


Modified radical mastectomy.

The recent history of operations for breast cancer indicates a growing trend toward conservatism. The modified radical mastectomy achieves the goal of removing all evidence of cancer in the breast involved and removes the regional lymph nodes for accurate staging of the disease. In addition, it provides a cosmetic result superior to that of the standard radical mastectomy. Breast reconstruction may be undertaken at a later time with excellent result. The 5 and 10 year survival rates of comparable groups of patients after modified radical mastectomy and standard radical mastectomy appear to be almost identical.


Ovarian suppression and breast cancer.

Castration by radiation or oophorectomy may cause regression of tumor metastasis. Patients who will benefit are those whose estrophile protein concentration in breast tissue is high. The use of castration as an early adjunctive method (prophylactic castration) delays the onset of recurrence, although it may take 10 to 15 years to verify these observations. Difficulty in analyzing these data is due to the smallness of the sample, and the frequent use of hormones in control patients. Effective castration may be observed with radiation or surgery. The choice is dependent on the patient's wishes and the need for an immediate effect. Combination therapy with steroids, chemotherapy, or adrenalectomy may potentiate the effect of castration. Premenopausal castration may markedly decrease the incidence of new breast cancers, particularly when followed for 20 or more years.


Bilateral breast cancer.

The true incidence of bilateral breast cancer, both simultaneous and subsequent, is higher than older statistics indicate, and the frequency can be expected to increase as more efficient methods of detection and treatment become commonplace. Furthermore, there is a subgroup of patients who have an especially high risk for having a second primary cancer in the other breast; if such a cancer develops it deleteriously influences the survival of the patient. A rational approach to the management of the other breast is presented using contralateral biopsy as an added modality for detection and reserving prophylatic matectomy of the other breast for those patients who ar at high risk for developing cancer in it.


Chemotherapy of recurrent breast cancer.

Several chemotherapeutic agents given singly or in combination are capable of producing significant tumor regression in recurrent breast cancer. Such remissions improve both the quality and duration of life. To date, the most active combinations have been variations of Cooper's CMFVP therapy or regimens containing Adriamycin. Further improvements in survival may be realized from the addition of hormonal and/or immune therapy to these active combinations as well as from the development of new drugs.


A technique for skin grafting of postmastectomy defects.

A technique for grafting defects at the site of the mastectomy uses full thickness grafts taken from the lower portion of the abdomen. Primary closure of the donor site can be achieved easily with minimal postoperative discomfort.


Platelets, thromboembolism and the clinical utility of antiplatelet drugs.

Experience has established a major role for platelets in the pathogenesis of a variety of thromboembolic disorders. Despite advances in several areas, many problems remain. The relevance of platelet function testing to thromboembolic disorders needs clarification. Whether the association of enhanced platelet function and the aforementioned disorders represents cause, effect or nonspecific accompaniment is unknown. The concept of identifying individuals at risk by platelet function testing is attractive but unproved. Whether such individuals would benefit from prophylactic antiplatelet therapy is also unknown. For treatment of most established thromboembolic disorders as well as prophylaxis, the place of antiplatelet drugs is not established. Whether this form of therapy is superior to conventional treatment, adjunctive or of no benefit is not resolved in most instances. Also, the most appropriate antiplatelet drug or combination of drugs, and in which dosages for specific disorders, remains unclear. Well designed, prospective clinical investigation, although cumbersome and time-consuming, will be necessary to answer most of these questions. A final problem area concerns research into the pharmacology of platelet inhibition. It is probable that the ideal antiplatelet agent remains undiscovered. Currently, several investigators are looking into the possibility of manipulating prostaglandin metabolic pathways in hopes of specifically blocking thromboxane generation while allowing production of metabolites inhibitory to aggregation. This exciting approach and other investigations into the biochemical basis of platelet function should lead to the discovery of new antiplatelet agents.


Corticosteroids in patients with a high risk of fat embolism syndrome.

The effects of methylprednisolone on the clinical fat embolism syndrome were studied in a series of 60 patients who had at least two fractures of the pelvis, femur and tibia and who did not have any other important injuries. This series was dichotomized at random, and 29 patients were given 10 milligrams per kilogram of methylprednisolone three times, once upon admission and, then, at eight and 16 hours post-traumatically. Thirty-one patients served as controls. Fat embolism syndrome was defined as a combination of hypoxemia, bilateral "snow storm" infiltrations of the lungs, petechial rash, mental disturbances, pyrexia, anemia and thrombocytopenia. Varying degrees of the syndrome were observed in two patients given methylprednisolone and in 15 patients in the control group. Methylprednisolone reduced all individual signs. There were no fatalities in this series of fracturers. No complications were observed from the use of methylprednisolone. Methylprednisolone in an early pharmacologic dosage is effective in fulminant instances of fat embolism that occur in spite of adequate respiratory care and the proper treatment of fractures.


Thoracoscopy in perspective.

The indications for thoracoscopy are undiagnosed pleural disease effusions of tumors; when tissue specificity is important for future treatment and adequate tissue is needed for estrogen binding studies; undiagnosed pleuropulmonary disease; biopsy of pulmonary lesions undiagnosed by other means; mediastinal masses, particularly in children; hilar masses; preoperative screening preliminary to thoracotomy for resection in malignant disease, particularly those with effusions; in spontaneous pneumothorax, to define the abnormality and indicate the need for thoracotomy; for postresection space problems; trauma, and, of course, for intrapleural pneumonolysis.


Tranexamic acid in the preoperative management of ruptured intracranial aneurysms.

A randomized, controlled clinical trial was carried out to study the effect of tranexamic acid (AMCA, trans-AMCHA) in prevention of early rebleeding after proven rupture of an intracranial aneurysm. The series comprises 46 patients admitted to the hospital within three days after the first bleeding. Twenty-three were treated with tranexamic acid and 23 were controls. Nine patients in the control group and one in the group treated with tranexamic acid had confirmed rebleeding. The incidence of vasospasm, cerebral ischemia and hydrocephalus as well as mortality and morbidity is discussed.


Humorally mediated alterations in cardiac performance as a consequence of positive end-expiratory pressure.

Two experimental designs were used to study the mechanism of the decreased cardiac output associated with the use of positive end-expiratory pressure (PEEP). In the first study of nine dogs the application of 15 cm H2O PEEP led to a decrease in cardiac output (CO) from 2.68 +/- 1.05 to 2.01 +/- 1.26 liters/min (+/- SD) (p less than 0.05) concomitant with an increase in transmural central venous pressure of 5.2 +/- 0.9 to 8.4 +/- 2.7 mm Hg (p less than 0.05) and a slight increase in transmural left atrial pressure of 6.8 +/- 3.3 to 7.3 +/- 3.6 mm Hg (p less than 0.1). These data are consistent with altered ventricular performance. In a second study nine pairs of dogs were cross-circulated. Application of 15 cm H2O PEEP to one member of the experimental pair led to a decrease in the CO of the other member from 2.71 +/- 0.98 to 2.21 +/- 0.81 liters/min (p less than 0.001). This decrease returned toward baseline with the removal of PEEP (p less than 0.02). Results indicate that one mechanism whereby PEEP reduces the cardiac output is through the action of a humoral agent.


Protective effect of propranolol in the treatment of ischemically damaged canine kidneys prior to transplantation.

Warm ischemia is a potential problem during the harvesting of cadaveric kidneys for transplantation purposes. This ischemia can cause impaired renal function following transplantation. The purpose of our study was to determine whether the beta-adrenergic blocking agent propranolol was effective in improving renal function after ischemia. Dog kidneys were subjected to 30 minutes of warm ischemia followed by hypothermic pulsatile preservation for 24 hours. The kidneys then were autotransplanted with immediate contralateral nephrectomy. In this model only 50% of the untreated control group survived. Three different protocols using propranolol were tested. Administration of propranolol to dogs before the ischemic period, or installation of propranolol into the renal artery at the start of the ischemia, or addition of propranolol to the preservation perfusate lessened the severity of acute tubular necrosis and resulted in 100% long-term survival. Although the mechanism was not investigated, it has been suggested that propranolol is acting through its blockade of beta-mediated renin release and/or through its so-called membrane-stabilizing effect.


A modified fundoplication which preserves the ability to belch.

This report describes a transabdominal antireflux procedure which combines some of the features of the operations described by Nisse, Belsey, and Hill. From 1972 through 1976, 61 patients underwent a conventional Nissen fundoplication and 54 patients were operated according to the method described in this report. None of the patients who had a Nissen operation was able to belch freely; 15% had a "gas-bloat syndrome". Return of the ability to belch often signified partial or complete brakdown of the plication, which occurred in 11% of the cases. By contrast, all but one of the patients who had modified plication were able to belch freely; there has been only one instance of recurrent reflux.


Portal hypertension following renal transplantation.

Portal hypertension and variceal hemorrhage may be found in the renal transplant patient with chronic liver disease. The development of portal hypertension was found to occur after long-term graft survival without significant rejection. The development of positive cytomegalic virus and negative hepatitis-associated antigen appeared to be common. Splenomegaly and prominent venous collateral were the most frequent physical findings, while ascites and hepatomegaly were less frequent. Portasystemic decompression can be performed successfully, however, the mortality and morbidity appear to be higher for this group than for other cirrhotic patients with comparable hepatic reserve.