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The use of epidemiology in documenting the mortality experience in complex emergencies has become pervasive in humanitarian practice. Recent assessments in Iraq and Darfur have provoked much discussion on the assessment of mortality in scientific and policy spheres. In this context, the Centre for Research on the Epidemiology of Disasters and the Harvard Humanitarian Initiative held an inter-disciplinary symposium to examine the topic among epidemiologists, demographers, forensic scientists and legal and human rights investigators.We aimed to strengthen the scientific understanding of mortality estimation by reviewing progress across fields and building inter-disciplinary bridges. We report on the presentations and discussions here.

Background: Group A Streptococcus (GAS) is an uncommon cause of infection after clean surgery in non-pregnant adults., Methods: Report of three cases and review of the literature. results: For the first time in France, severe GAS infections were observed in three patients who underwent thyroidectomy at three hospitals. Two of them developed streptococcal toxic shock syndrome., Conclusion: Better knowledge of physiopathologic mechanisms would help in the detection and prevention of severe GAS infections.

Objective: To assess the pattern of diseases in a natural disaster, which are not necessarily a direct consequence of the event but can impact on the way health assistance is to be provided., Methods: Cross-sectional, record-based study in the International Committee of the Red Cross field hospital in Aceh, Indonesia, established immediately after the tsunami in 2004. Patients who presented to hospital from January 15 to 31, and whose diagnoses were available, were included in the study., Results: One thousand one hundred and eighty-eight residents of Aceh participated. 43.5% of the diagnoses was chronic diseases. The odds of chronic vs. acute diseases increased by 16.4% per day up to January 23 [95% confidence interval (CI): 7.8-25.6%] and decreased thereafter by 13.1% (95% CI: 6.6-19.1%) per day. The odds of acute diseases were 34% lower among females than males (95% CI: 16-49%) and 4.3 times higher among children than the rest of the population (95% CI: 2.4-7.6). There were relatively few trauma cases among females and children., Conclusions: Medical teams providing relief after acute disasters should be prepared to provide healthcare for chronic diseases too. A delay in the presentation of many acute conditions has implications for long-term health consequences of disasters, such as disability.

Dengue is the most important arthropod-borne viral disease of public health significance. Compared with nine reporting countries in the 1950s, today the geographic distribution includes more than 100 countries worldwide. Many of these had not reported dengue for 20 or more years and several have no known history of the disease. The World Health Organization estimates that more than 2.5 billion people are at risk of dengue infection. First recognised in the 1950s, it has become a leading cause of child mortality in several Asian and South American countries.This paper reviews the changing epidemiology of the disease, focusing on host and societal factors and drawing on national and regional journals as well as international publications. It does not include vaccine and vector issues. We have selected areas where the literature raises challenges to prevailing views and those that are key for improved service delivery in poor countries.Shifts in modal age, rural spread, and social and biological determinants of race- and sex-related susceptibility have major implications for health services. Behavioural risk factors, individual determinants of outcome and leading indicators of severe illness are poorly understood, compromising effectiveness of control programmes. Early detection and case management practices were noted as a critical factor for survival. Inadequacy of sound statistical methods compromised conclusions on case fatality or disease-specific mortality rates, especially since the data were often based on hospitalised patients who actively sought care in tertiary centres.Well-targeted operational research, such as population-based epidemiological studies with clear operational objectives, is urgently needed to make progress in control and prevention.

Mortality rates are among the main indicators of the human impact of armed conflict and many surveys have assessed this impact both for targeting and evaluating humanitarian aid programmes. Almost no epidemiological analysis such as calculating relative risk was performed nor were reference values clearly described. Here the aim is to review published mortality rates for a better understanding of age-specific mortality in armed conflict. Published mortality rates from conflict situations were collected and pre-conflict reference rates composed. We calculated the relative risk of dying in conflict compared to pre-conflict for children under 5 and people older than five years old. Although limited by reporting inadequacies, the results confirm the high vulnerability of children < 5 but identify a higher relative risk of dying among the > or = 5 year olds. Although not entirely new, this observation is not fully understood. Further systematic epidemiological research is needed to estimate and understand the impact of armed conflict on mortality.

Background: Epoetin alfa (Eprex*; Johnson & Johnson, Manati, PR) has been used successfully to correct the anemia of chronic renal failure for more than 12 years. Anti-erythropoietin (anti-EPO) antibodies have been reported in a small number of patients, resulting in a blood disorder, pure red cell aplasia (PRCA). To evaluate the utility of a large-scale anti-EPO antibody screening program in patients with chronic kidney disease (CKD) administered epoetin alfa, a study involving 5 large renal centers in southern Ontario, Canada, was conducted., Methods: More than 1,500 hemodialysis, peritoneal dialysis, and predialysis patients were screened for the prevalence of anti-EPO antibodies by means of a radioimmunoprecipitation (RIP) assay. Serum samples were drawn and shipped to PPD Development (Richmond, VA) for the immunoprecipitation assay. Serum EPO levels also were measured. All samples that tested positive or borderline for antibodies were sent to MDS Pharma Services (Montreal, Canada) for the neutralization assay., Results: Of 1,531 samples tested, 1 patient tested low-positive and 3 borderline results were detected by means of RIP. PRCA previously was diagnosed in the patient with the low-positive antibody level; the patient was treated with cyclosporine and currently is being administered epoetin alfa with good response. The 3 patients with borderline antibody results manifested no clinical signs of PRCA. Neutralization assays performed on all 4 serum samples were negative for anti-EPO antibodies., Conclusion: Results from this surveillance study show that the prevalence of antibody to EPO in patients with CKD administered epoetin alfa in 5 Canadian renal centers is low, and the value of a large-scale antibody screening program for PRCA cannot be justified.

Civil conflict affects the health of individuals in many countries, and draws a substantial amount of international humanitarian aid. The most widely used indicator of the effect of conflict is the rate of civilian death during conflict. We aimed to assess mortality estimates from conflicts in Sudan, Somalia, the Democratic Republic of Congo, and Afghanistan by calculating the relative risk of death during and after conflict compared with that in preconflict peacetime. Katale, in the Democratic Republic of Congo, had the highest relative risk of death during conflict (11.2 [9.1-13.8] and 103.3 [94.7-112.6], for children younger than 5 years and the whole population, respectively). Our results suggest that high rates of civilian mortality are determined more by the pre-existing fragility of the affected population than the intensity of the conflict. In many instances, a high rate of civilian deaths during conflict shows that international development aid before the conflict was grossly inadequate.

This article reports the case of a 33-year-old woman with common variable immunodeficiency (CVI) who developed renal failure 17 years after diagnosis and initiation of treatment with monthly IVIG. A renal biopsy revealed mesangial and paramesangial immune complex deposition and interstitial granulomatous infiltration. Renal function improved with oral corticosteroids, but did not return to normal. Decreasing the dose of IVIG had no effect on renal function. Immune dysfunction can be associated with both granulomatous disease and immune complex glomerulonephritis, or the latter may be related to chronic infection or immunoglobulin use. This is the first report of concomitant glomerular-tubulointerstitial lesions in this immunodeficiency syndrome. Renal function should be closely followed in patients with CVI.

Purpose: To assess the efficacy of gemcitabine in patients with a variety of sarcomas that have failed to respond or escaped Adriamycin- and ifosfamide-based chemotherapy., Patients and Methods: A group of 18 symptomatic heavily pretreated patients with sarcomas of bone or soft tissue received one induction course of gemcitabine at a dose of 1000 mg/m(2) per week for 7 consecutive weeks, followed by 1 week rest. Response to the induction course was assessed by interview and by repeated ancillary tests. If no progression was observed, maintenance by gemcitabine 1000 mg/m(2) per week for 3 weeks every 28 days was given until failure was clinically or radiologically evident., Results: A total of 51 cycles of gemcitabine were given including 18 cycles of induction. A mean of 3.6 postinduction cycles were given to nine patients. The treatment was well tolerated by the patients. One partial response (leiomyosarcoma) and one minimal response (angiosarcoma) were observed, yielding a true objective response rate of 5.5%. An additional six patients achieved stabilization of disease (chondrosarcoma and osteosarcoma), yielding an overall progression-free rate of 44%. The median time to progression was more than 27 weeks. Clinical benefit response was observed only in those who also achieved a progression-free state., Conclusion: Gemcitabine was found to be effective in achieving stabilization and even a minimal response of soft tissue or bone sarcoma refractory to standard chemotherapy.

Well-differentiated thyroid cancer is the most common malignancy of the thyroid gland, yet its optimal management remains controversial. 269 patients with such lesions were operated on, with or without supplementary treatment. It was concluded that young patients with stage I disease can be safely treated by subtotal thyroidectomy. Total thyroidectomy combined with radioactive ablation is indicated in patients with more advanced systemic disease.

Since 1980, over 2 million people have died as an immediate result of natural and man-made disasters and by 1992, the refugee population registered nearly 16 million people. This article reviews the human impact of disasters as a composite of two elements: the catastrophic event itself and the vulnerability of people. It also examines the specific case of women and children in the current world emergency context. It identifies four broad policy areas that affect women and children in disaster situations and discusses them with examples and field evidence. The first policy area addresses humanitarian assistance and armed conflicts, and armed conflict and international humanitarian law, the use of food as instrument of war, mines and civilian disability, and rape and sexual violence are discussed within this context. The second problem discussed is the issue of unaccompanied and abandoned children in terms of its magnitude and implications for relief response. Thirdly, the article examines the differential risks in emergencies for mortality and morbidity, specifically for women and children. Finally, it addresses certain policies and approaches to disaster rehabilitation which effectively mirror and reinforce inherent inequities in the affected society. The article notes that: (i) the largest proportion of disaster victims today arise from civil strife and food crises and that the majority of those killed, wounded and permanently disabled are women and children; and (ii) the ability of any country to respond effectively to disasters depends on the strength of its health and social infrastructure, and its overall developmental status. It concludes by identifying seven areas where concrete measures could be taken to improve the current situation.

The increase in the number of natural disasters and their impact on population is of growing concern to countries at risk and agencies involved in health and humanitarian action. The numbers of persons killed or disabled as a result of earthquakes, cyclones, floods and famines have reached record levels in the last decade. Population density, rampant urbanization and climatic changes have brought about risk patterns that are exposing larger and larger sections of populations in developing countries to life-threatening natural disasters. Despite substantial spending on emergency relief, the approaches to relief remain largely ad hoc and amateurish, resulting generally in inappropriate and/or delayed action. In recent years, mass emergencies of the kind experienced in Bangladesh or the Sahelian countries have highlighted the importance of rapid assessment of health needs for better allocation of resources and relief management. As a result, the development of techniques for rapid assessment of health needs has been identified as a priority for effective emergency action. This article sketches the health context of disasters in terms of mortality and morbidity patterns; it describes initial assessment techniques currently used and their methodological biases and constraints; it also discusses assessment needs which vary between different types of disasters and the time frame within which assessments are undertaken. Earthquakes, cyclones, famines, epidemics or refugees all have specific risk profiles and emergency conditions which differ for each situation. Vulnerability to mortality changes according to age and occupation, for earthquakes and famines. These risk factors then have significant implications for the design of rapid assessment protocols and checklists. Experiences from the field in rapid survey techniques and estimation of death rates are discussed, with emphasis on the need for a reliable denominator even for the roughest assessment. Finally, the importance of adapting normal epidemiological and statistical methodologies to crisis situations is underlined in order to rationalize the recurrent and substantial expenditures made in response to natural disasters today.

Recently published studies vary widely in the quantitative assessment of glomerular filtration rate (GFR) in lithium-treated patients. Therefore, the authors tested 99 lithium-treated manic-depressive patients using several techniques to measure GFR. Ten of 86 patients who had no history of renal disease had mildly low creatinine clearance values. Significant correlations, which were not age-related, between the serum creatinine, Cockroft creatinine clearance, and duration of lithium therapy suggest a relationship between chronic lithium therapy and declining GFR. Since serum creatinine alone was insensitive, the authors recommend the use of duplicate classical creatinine clearances confirmed by Cockroft values to monitor GFR during lithium treatment.

The alpha-ketoanalogues of the branched-chain amino acids were administered to fasting subjects to determine whether or not they promoted nitrogen sparing. Two fasting studies were carried out in each subject. During the first week of one of the two fasts 4.7 g of a mixture of the alpha-ketoanalogues of valine, leucine, and isoleucine were infused daily. No infusions were administered during the other fast, which served as a control. Urinary urea and calculated total urinary nitrogen were significantly lower during both the week of infusions and the ensuing week of fasting after the infusions were discontinued. Immediately after ketoacid infusions, plasma branched-chain amino acids, including allosioleucine, rose, while alanine and several other amino acids (but not glutamine) fell. There were no differences between the two fasts with respect to ketone bodies, free fatty acids, glucose, insulin, or glucagon concentrations. We conclude that branched-chain ketoacids spare nitrogen early in fasting and that this effect persists after they are metabolized.

The safety and efficacy of captopril in geriatric patients with mild to moderate hypertension was examined in an eight-week multicenter study of 99 patients. Following a placebo period, patients were treated with captopril 25 mg twice daily. Patients who were uncontrolled after two weeks of active therapy were randomized to either captopril 25 mg plus hydrochlorothiazide 15 mg or captopril 50 mg twice daily. The average decrease in blood pressure at study completion was--16.9/11.9 mmHg. At the conclusion of the trial, 75.8% of patients responded to therapy. Captopril was well tolerated and believed to be a good therapeutic alternative for treating hypertension in the elderly population.

Renal handling of acetoacetate and beta-hydroxybutyrate was studied in 12 obese subjects undergoing total starvation. Simultaneously, the acetoacetate, beta-hydroxybutyrate, and inulin clearance rates were measured, and acetoacetate and beta-hydroxybutyrate reabsorption rates were calculated. Renal clearance of blood acetoacetate and beta-hydroxybutyrate remained constant. In contrast, acetoacetate reabsorption rate increased significantly from 47 plus or minus 10 mumoles/min on day 3 to 106 plus or minus 15, 89 plus or minus 10, and 96 plus or minus 10 mumoles/min on days 10, 17, and 24, respectively. Similarly, beta-hydroxybutyrate reabsorption rate increased significantly from 154 plus or minus 27 mumoles/min on day 3 to 419 plus or minus 53, 399 plus or minus 25, and 436 plus or minus 53 mumoles/min on days 10, 17, and 24, respectively. Both acetoacetate and beta-hydroxybutyrate reabsorption rates increased linearly when plotted against their filtered loads. Thus, no tubular maximal transport rate exists for acetoacetate or beta-hydroxybutyrate during physiologic ketonemia. Conservation 450-500 mmoles of ketone bodies/day prevents large urinary losses of cations during prolonged starvation. Since ammonium becomes the major cation excreted during prolonged fasting, the increased renal reabsorption of ketone bodies minimizes body protein loss and aids in maintaining high circulating acetoacetate and beta-hydroxybutyrate concentrations.

Forty lithium-treated manic-depressive patients underwent two renal function assessments 6 to 18 months apart to assess the course of renal function changes associated with lithium therapy. No change in glomerular filtration rate was noted. Although the average 24-hour urine volume increased significantly, large increases occurred in few patients. Most patients had no substantial urine volume change, and a few had decreases. The changes were correlated with serum lithium levels. The results suggest that the majority of patients develop little renal concentrating impairment, while a small proportion of patients become more polyuric with further lithium treatment.

Unilateral renal vein thrombosis occurred in a patient who was found to have an adenocarcinoma and who had previously been subjected to trauma. Proteinuria was absent throughout the patient's entire clinical course, despite its well known association with renal vein thrombosis. However, other findings suggestive of renal vein thrombosis, including back pain and tenderness, hematuria and an enlarged kidney were present. It is clear that proteinuria need not be the only signal to occasion a search for renal thrombosis. This case probably constitutes the second report of absent proteinuria when thrombus forms within renal vein.

21 patients undergoing major abdominal surgery were randomly assigned to one of three groups. On the day of surgery and for the succeeding 4 days each group received a daily infusion of one of the following: 10 g glucose plus 70 mmol NaHCO3, 70 mmol leucine plus 70 mmol NaHCO3, or 70 mmol of sodium alpha-ketoisocaproate (KIC). No other calories were given. Leucine infusions had no significant effect on nitrogen (N) balance, 3-methylhistidine excretion, or plasma concentrations of pre-albumin or retinol-binding protein, but they increased blood acetoacetate concentration (p = 0.004). N balance was less negative (p = 0.002) and 3-methylhistidine excretion lower (p = 0.002) in the group receiving KIC than in those receiving glucose. Blood ketone bodies, plasma prealbumin, and plasma retinol-binding protein concentrations at the end of the study were significantly higher in the KIC group than in the others. These N-sparing effects of KIC may be related to the heightened ketosis that followed its administration, to suppression of protein degradation, or to an effect on liver protein turnover. KIC alone in small doses diminishes N wastage in postoperative but under the same conditions leucine does not.

This report presents three cases of 'cured' rectal cancer which developed solitary lung metastases during the follow-up period. Further metastatic work-up did not disclose any evidence of disease. Neurological examination was normal. Surgical resection of the pulmonary metastases was done. Brain metastases were discovered a short time after. The importance of the CT scan of the brain in the pre-operative work-up is discussed.

Nitrogen-free analogues of essential amino acids, when administered with those essential amino acids for which analogues are ineffective or unavailable, exert three actions that may be beneficial in protein-deficient or protein-intolerant subjects. First, they bring about an increase in the concentrations of essential amino acids in the blood at the expense of the concentrations of certain non-essential amino acids, notably alanine and glutamine. This effect is most readily demonstrated in children with congenital defects of the urea cycle enzymes, but can also be seen during daily therapy of adults with portal-systemic encephalopathy. Second, these compounds promote nitrogen balance through their suppressive effect on urea synthesis (an effect not attributable to re-utilization of ammonia derived from urease action in the gut). This action is demonstrable in obese subjects who are already conserving nitrogen maximally at the end of a prolonged fast and can also be shown in the first week of fasting when the branched-chain keto acids alone are administered. In both situations, improved nitrogen conservation persists long after the analogues are metabolized, suggesting enzyme adaptations. In chronic uremics, nitrogen balance can be maintained in some (but not all) patients on very low nitrogen intakes. Third, these mixtures may delay or reverse the progressive decline in glomerular filtration rate characteristic of chronic renal failure in some cases: thus, for example, 5 of 6 patients taken off chronic dialysis have maintained lower serum urea concentrations without evidence of protein malnutrition for periods of 2-24 months.

The paper addresses the issue of information in disasters relief. It begins by establishing the need for planning and systematic organization in disaster action, in order to produce a long term effect on the vulnerability levels of communities. Information is introduced as a key element in any phase of disaster management. The different informational needs are described by phases; information types and possible sources are briefly described. The organizational network of information collection is presented and the immediate need for research in this field is emphasized.

Administration of KC1 0.5 mmol/kg/day to subjects undergoin prolonged starvation reduced daily urinary ammonium and beta-hydroxybutyrate excretion by one-third. These changes were accompanied by an improvement in potassium balance and an increased rate of chloride excretion. A similar fall in ammonium excretion occurred in a second group of subjects after administration of KHCO3 0.5 mmol/kg/day. Ketone body and bicarbonate excretion remained unchanged in this group while potassium balance improved. In both the first and second groups urine pH fell significantly as the rate of excretion of urinary buffer (ammonium) decreased. When the dose of KHCO3 was increased to 1.5-2.0 mmol/kg/day in fasting subjects, the urine was alkalinized, and ammonium excretion fell to negligible levels, resulting in nitrogen sparing of 2.0 g/day. The results indicate that one-half of the increase in ammonium excretion observed in starvation is due to potassium deficiency. Nitrogen wastage caused by losses of urinary ammonium during starvation can be virtually eliminated by potassium supplementation and urinary alkalinization. The decrease in beta-hydroxybutyrate excretion after potassium chloride administration was not caused by a fall in the rate of nonionic diffusion of this organic acid related to the reduction in urine pH. The reason for the fall in beta-hydroxybutyrate excretion is not apparent, though it was associated with an increase in chloride excretion.

The relation of prognostic factors to survival was analyzed in 352 consecutive lung cancer patients referred to the Northern Israel Oncology Center between the years 1978 and 1981. Of these patients 328 died and only 19 (5.5%) were alive with no evidence of disease after a minimum follow-up period of 70 months. Univariate analysis with Kaplan-Meier plots was used to evaluate 63 pretreatment clinical factors. Mode of treatment, the quality of response and time to response were also evaluated for correlation with survival. The following parameters were found to have a significant association with mortality: presence of brain metastases (P less than 0.001), age greater than 60 years (P less than 0.001), Karnofsky performance status less than 80% (P less than 0.001), weight loss (P less than 0.001), and extensive disease (P less than 0.001). Treatment by surgery (lobectomy) was associated with longer survival (P less than 0.001). Other factors were found to have no significant relation to survival. The above data might be of value for patient randomization in future clinical trials.

1. Administration of dexamethasone, 8 mg/day (0-02 mmol/day), for 5 days to normal subjects produced negative nitrogen balance, due to early and sustained increases in urinary urea nitrogen excretion 2. In eight subjects ingesting 0-9--1-6 g of protein day-1 kg-1 body weight the cumulative increment in urea nitrogen excretion averaged + 12-5 g (SEM 2-8, P less than 0-01) over the 5 days of glucocorticoid administration. 3. Increases in urinary urea nitrogen excretion could be related to both plasma alanine and blood glutamine changes by using a multiple regression equation. 4. These results suggest that corticosteroids induce increased release of alanine and glutamine by peripheral tissues, which may augment urea formation and negative nitrogen balance. 5. The correlation between increments in urea nitrogen excretion and increases in plasma arginine remains unexplained.

This study was carried out in seven patients being treated by intermittent hemodialysis. Each had some residual renal function. In protocol 1, when the patients were dialyzed weekly and the dietary protein intake was 0.96 g/kg/day, the nitrogen balance corrected for changes in the urea pool was positive during the days between dialysis; the serum urea concentration (SUN) before dialysis was 109 +/- 7 mg/dl. In protocol 2, when dietary protein was reduced to 0.4 g/kg/day and supplemented with essential amino acids (10 g/day), the corrected nitrogen balance on days between weekly dialyses was positive; the SUN before dialysis was lower than it was in protocol 1 (-33 +/- 7 mg/dl, P less than 0.01). The nonurea space (body weight minus body water) increased in six of seven patients during protocol 2. Two patients were then treated with the dietary regimen of protocol 2 and dialyzed every 2 weeks. The corrected nitrogen balance on nondialysis days was positive, and there was a further increase in nonurea space. This study suggests that dialysis frequency may be reduced in some patients with residual renal function by means of nutritional therapy.

Seven cases of soft tissue sarcoma developing after primary or postoperative radiotherapy for breast carcinoma are reported. The sarcomas occurred within the irradiated volume, after a latent period of 4-26 years. These cases conform well to established criteria for the diagnosis of radiation-induced sarcoma. Chemotherapy, consisting of the four-drug combination CYVADIC (cyclophosphamide, vincristine, adriamycin, DTIC) was employed in six of the seven patients. Only two of them achieved partial remission, lasting only 2 and 3 months, respectively. The effectiveness of adriamycin-containing chemotherapy regimens in soft tissue sarcomas as well as the remote hazard of radiation-related sarcoma in primary or postoperative breast irradiation are discussed.

Eleven cases of renal failure associated with resection of ruptured abdominal aortic aneurysm and requiring hemodialysis are reported. Previously described series have emphasized the extremely high mortality rate in such patients. In our clinical experience, however, 8 of 11 consecutively treated patients with this clinical problem survived and recovered adequate renal function. We believe that these favorable results can be largely explained by the low incidence of pulmonary infection in our patients as opposed to the frequent occurrence of pulmonary sepsis in other reported series. The reduction in the incidence of pulmonary infection can probably be attributed to the early discontinuance of artificial ventilation after prompt removal of pulmonary edema fluid by intensive hemodialysis ultrafiltration. These survival figures demonstrate that, with appropriate intensive management, full recovery is possible in the majority of patients with acute renal failure complicating ruptured aortic abdominal aneurysm. Our experience serves as a stimulus to render full intensive care support to such patients.

In a study of 445 patients with colorectal cancer referred to our center during a 3-yr period, we investigated the following parameters and their interrelationships: sex, marital status, ethnic origin, place of residence, stage of disease, delay in diagnosis and factors responsible for delay. Localized disease was found in 52% of the patients, regional disease in 29% and metastatic disease in 19%. The incidence of colorectal cancer was significantly higher in Jews of European (occidental) descent than in Jews of Asian or North African (oriental) descent or in Arabs. The median and mean ages were significantly higher in the occidental than in the oriental Jewish group and significantly lower in the Arabs than in the oriental Jews. Diagnosis was delayed for more than 6 weeks in 52% of the patients. Responsibility for the delay could be attributed to the patient in 54% of these cases and to the physician in 47%. Administrative factors were responsible for the delay in 26%. (In 27% of the above delayers there was more than one agent responsible for the delay.) On average, patients in whom diagnosis was delayed had more advanced disease than those without delay. Also, patients with advanced disease had a longer delay on average than those with localized disease. The stage of disease at diagnosis was more advanced in the oriental than in the occidental Jews. No correlations were found between delay in diagnosis and either age or sex. There were more widowers with delay (21%) than with no delay (16%). In patients living outside Haifa delay was more prolonged than in those residing in the city. Educational programs aimed at the population at risk of developing neoplasm and especially at those likely to undergo delay in diagnosis are recommended. Postgraduate courses should be designed to instruct physicians on how to minimize delay in diagnosis.

11 normal obese subjects were fasted for 33 days. In five, who served as controls, urine urea nitrogen excretion remained constant for 2 wk thereafter. The other six were given seven daily infusions containing 6-8 mmol each of the alpha-keto-analogues of valine, leucine, isoleucine, phenylalanine, and methionine (as sodium salts) plus 3-4 mmol each of the remaining essential amino acids (lysine, threonine, tryptophan, and histidine). Rapid amination of the infused ketoacids occurred, as indicated by significant increases in plasma concentrations of valine, leucine, isoleucine, alloisoleucine, phenylalanine, and methionine. Glutamine, glycine, serine, glutamate, and taurine fell significantly. Blood glucose, ketone bodies, plasma free fatty acids, and serum immunoreactive insulin concentrations were unaltered. Urine urea nitrogen fell from 1.46 to 0.89 g/day on the last day of infusions; 5 days later it was still lower (0.63 g/day) and in two subjects studied for 9 and 17 days postinfusion it remained below preinfusion control values. Urine ammonia, creatinine, and uric acid were unaltered. Nitrogen balance became less negative during and after infusions. The results indicate that this mixture of essential amino acids and their keto-analogues facilitates nitrogen sparing during prolonged starvation, in part by conversion of the ketoacids to amino acids and in part by altering mechanisms of nitrogen conservation. The latter effect persists after the ketoacids are metabolized.

A 3-year experience with 50 acute renal failure patients managed by hemodialysis in a 417-bed community hospital is reviewed. The 58% survival rate was better than that reported in other recent series. Possible reasons for our favorable mortality experience include: (1) Hemodialysis was performed within the ICU facility by the ICU staff. Continuity of total care was thereby maintained and hemodialysis problems, such as maintenance of circulating volume, were managed in the context of continued assessment of the patient's cardiopulmonary status. (2) In contrast to previous reports, the presence of sepsis did not influence recovery rates from acute renal failure. Early administration of specific antibiotics, mainly gentamicin, rapid drainage of abdominal abscesses, and early and frequent dialysis were all utilized in spetic patients and may have contributed to their high recovery rate. (3) The use of agressive dialysis may also have lessened other uremic complications, notably gastrointestinal bleeding. Our dialysis organization and procedures are described.

We have carried out balance studies in normal dogs in order to appraise the effects of chronic hypoxemia on acid-base and electrolyte equilibrium. During the first phase of observation we produced a state of "pure" hypoxemia by reducing the oxygen concentration (utilizing nitrogen as a diluent) and by adding carbon dioxide to the environment in a concentration sufficient to keep arterial CO(2) tension (PCO(2)) within normal limits. The data demonstrate that such a 9-day period of normocapneic hypoxemia has no effect on electrolyte excretion and is virtually without effect on plasma composition. During the second phase of observation we subjected the hypoxemic dogs to stepwise increments in arterial carbon dioxide tension in order to evaluate the effects of the low oxygen tension on the acid-base adjustments to a chronic state of hypercapnia. At least 6 days was allowed for extracellular composition to reach a new steady state at each level of inspired carbon dioxide. The data demonstrate a rise in both plasma bicarbonate concentration and renal acid excretion that was not significantly different from that which has been described previously for hypercapnia without hypoxemia. Just as in these earlier studies, plasma hydrogen ion concentration rose with each increment in carbon dioxide tension, each millimeter Hg increment in PCO(2) leading to an increase in hydrogen ion concentration of 0.32 nmole per L. It thus appears that the chronic"carbon dioxide response curve" is not significantly influenced by moderately severe hypoxemia.

The metabolic effects of oral ingestion of minute quantities of carbohydrate during prolonged starvation were studied in nine obese subjects. Measurements were made during a control period of total starvation, during the ingestion of 7.5 g carbohydrate daily, and finally during the ingestion of 15.0 g carbohydrate daily. Daily ketoacid excretion fell after carbohydrate ingestion and was significantly correlated (r = 0.62, P < 0.01) with the amount of carbohydrate administered. Despite this fall in ketoacids, the concentration of blood ketoacids, plasma free fatty acids, and serum insulin remained constant throughout the study. Urinary ammonium excretion, closely correlated with ketoacid output (r = 0.95, P < 0.001), also fell significantly after carbohydrate ingestion. No significant changes were present in extracellular or urinary pH. Urea nitrogen excretion did not change when urinary ammonium output fell. These results indicate that: the excretion of ketoacids and ammonium in starving man is exquisitely sensitive to minute amounts of ingested carbohydrate; the change in ketonuria appears to be due to increased renal ketoacid reabsorption after carbohydrate ingestion; and the nitrogen-sparing effect of reducing renal ammonium output in starvation can be dissociated from nitrogen sparing occurring because of changes in urine urea excretion.