Summertime pneumonias in Philadelphia in 1976. An epidemiologic study. Summertime pneumonias in Philadelphia during 1976 were studied epidemiologically, and the epidemiologic, clinical, and laboratory features of pneumonia cases serologically positive for Legionnaires' disease were compared with features of serologically negative cases. Both groups were similar in many respects, but in patients with Legionnaires' disease diarrhea and neurologic findings were significantly more frequent (P = 0.01 and P = 0.05 respectively). A diagnosis of Legionnaires' disease was also suggested by an elevated serum creatinine phosphokinase level (P = 0.02) and the presence of occult blood in the urine with fewer than six erythrocytes per highpower field. Abnormalities in renal function tests or liver function tests were commoner in patients with Legionnaires' disease (P = 0.05). Radiographic features, however, could not be used to separate pneumonia cases. The high frequency of extrapulmonary manifestations involving the gastrointestinal tract, the central nervous system, kidneys, and liver suggests that Legionnaires' disease is a multisystemic disorder possibly caused by a toxin-producing organism.


Legionnaires' disease in Nottingham, England. Legionnaires' disease bacterium was identified as the cause of severe pneumonia in some Nottingham, England, patients in 1977. Laboratory studies were not restricted to Nottingham but included several other areas in England. The 41 cases identified were evenly divided between areas; they also accounted for about one half of all cases for the entire country. No source of infection has been identified in these sporadic cases. There was no contact between patients, and only a few had travelled abroad before their illnesses. Serologic sampling of populations in Nottingham did not reveal a large background of infection. Only 31 of 2023 sera tested had low titer antibody to the Pontiac antigen used. Guinea-pig antisera to two positive lung extracts showed an antigenic relation to the Pontiac but not to the Togus strain,suggesting strain variation.


A major focus of Legionnaires' disease in Bloomington, Indiana. Thirty-nine cases of Legionnaires' disease in a 16-month period were identified in visitors to and residents of Bloomington, Indiana. Thirty-five patients had spent at least one night at the Indiana Memorial Union in the 2 weeks before becoming ill. Five of 32 sporadic cases nationwide between 1 January and 31 March 1978 were retrospectively shown to be in persons who had recently visited the Union. The risk of acquiring Legionnaires' disease as a Union visitor was at least 17 times greater than that for Bloomington residents 20 years or older. Employees who had worked at the Union 5 years or longer were more likely to be seropositive than workers in other Bloomington hotels. Legionnaires' disease bacterium was isolated from five environmental sites in Bloomington. A cooling tower may have been involved in disease spread, but it was not the only source. Hypochlorite solution was added to cooling tower water as a precautionary measure; however, one case was confirmed in a man with Union exposure 9 days after hypochlorite treatment had begun.


Sporadic cases of Legionnaires' disease in Great Britain. Data on sporadic cases of Legionnaires' disease in Great Britain reported to the Communicable Disease Surveillance Centre, London, and the Communicable Diseases (Scotland) Unit, Glasgow, were analysed. Eighty-four cases, including 18 patients who died, were identified with dates of onset between 1 January 1976 and 30 September 1978. The age and sex distribution showed a predominance of middle-aged men. The incidence trends suggest that true seasonal variation may occur. Eighteen patients developed illness during or shortly after a holiday abroad. All patients had pneumonia, but many also had features suggesting involvement of the central nervous system and gastrointestinal tract. Person-to-person spread was not observed.


Sporadic community-acquired Legionnaires' disease in the United States. A case-control study. One hundred patients with sporadic, community-acquired, serologically confirmed Legionnaires' disease were matched with control subjects known by the patients (acquaintance controls) and control subjects chosen from among patients with negative serodiagnostic tests for Legionnaires' disease (clinical controls). Each clinical control subject was also matched with an acquaintance control of his own. Legionnaires' disease patients had smoked more cigarettes, consumed more alcohol, and were more likely to have resided near excavation sites than acquaintance or clinical control subjects. Parallel differences between clinical controls and their acquaintances were not seen. Legionnaires' disease patients had traveled away from home for more time during the 2 weeks before onset of illness than had their acquaintances. The difference was of greater magnitude than that between clinical control subjects and their acquaintances. Legionnaires' disease patients were more likely to have resided near construction sites than clinical controls, and there were more construction workers among patients than among clinical control subjects.


Prevalence of antibody to the Legionnaires' disease bacterium in hospital employees. A sereopidemiologic survey was done to ascertain the level of immunity in a population of hospital employees after contact with patients with Legionnaires' disease. Two matched groups were compared: hospital staff in positions of contact with patients diagnosed with the disease (N1 = 215), and hospital staff not in a position of contact with patients diagnosed with Legionnaires' disease (N2 = 269). Antibody titer was measured by the hemagglutination technique. Subjects from N1 and N2 were surveyed for age, sex, race, smoking, patient care unit, air conditioning unit, occupation, symptoms, and patient contact. No significant correlation was found between titer distribution and any one of the first seven factors. The prevalence of antibody (greater than or equal to 128) was 9.3% and 3.7% (P less than 0.02) for the N1 and N2 groups. Also, 40% of employees with titers of 128 or above had had an unexplained febrile respiratory illness in the preceding year. This study suggests the possibility of person-to-person transmission in Legionnaires' disease.


Legionnaires' disease in pneumonia patients in Iowa. A retrospective seroepidemiologic study, 1972-1977. The frequency of Legionnaires' disease among 586 cases of pneumonia that occurred in Iowa between fiscal years 1972 and 1977 was studied retrospectively on the basis of paired sera. The frequency of confirmed Legionnaires' disease was 4.1% and of presumptive Legionnaires' disease was 11.4%. Infections with the Legionnaires' disease (LD) bacterium were most frequent in the summer. Of the 22% of pneumonias for which a cause could be defined, Legionnaires' disease was third in frequency behind Mycoplasma pneumoniae and influenza A virus infections. Infections with the LD bacterium occurred in association with pneumonias in most age groups. The youngest patient with LD infection was a 5-year-old boy with pneumonia. The disease occurred 3.2 times more often in males than in females. In males, the frequency of confirmed and presumptive Legionnaires' disease increased steadily to plateau after the fourth decade at about 12% and 28%, respectively. In females the frequency of presumptive Legionnaires' disease was 7% to 16%, relatively evenly distributed over all age groups. Pneumonias associated with LD bacterium infection should be considered in the differential diagnosis of community-acquired pneumonias in most age groups.


Relation of Mycoplasma pneumoniae seroreactivity, immunosuppression, and chronic disease to Legionnaires' disease. A twelve-month prospective study of sporadic cases in Massachusetts. From April 1977 through March 1978, 28 presumptive cases of Legionnaires' disease were identified among 432 consecutive candidates having paired sera or tissue samples submitted to the Massachusetts Public Health Laboratories. Among the subgroup of 209 candidates with documented diffuse pneumonia and temperature of 39 degrees C or above, 24 (11.5%) had Legionnaires' disease whereas the diagnostic yield was only four of 223 (1.8%) among the remainder. The case-fatality rate was two of 28 (7%). Patients with Legionnaires' disease when compared to the entire group of candidates were similar in mean age (49 versus 48 years) and frequency of immunosuppressant therapy (15% versus 12%) but were more often male (64% versus 47%) with underlying chronic illness (46% versus 22%). Complement fixation tests against Mycoplasma pneumoniae (whole organisms) showed seroreactivity in 81% of Legionnaires' disease (LD) cases (22 to 27) compared to 13% of non-LD cases; conversely, 29% of all cases seropositive for M. pneumoniae (22 of 75) were seropositive for the LD bacterium compared to only 1% (five of 357) of the remainder. The coincidence of seroreactivity for M. pneumoniae and the LD bacterium is unexplained but suggests that M. pneumoniae seropositive cases should be evaluated for the possibility of Legionnaires' disease.


Fatal nosocomial Legionnaires' disease: clinical and epidemiologic characteristics. The occurrence, clinical, and epidemiologic characteristics of fatal nosocomial Legionnaires' disease were ascertained by examining a sample of autopsy specimens submitted by hospitals participating in the National Nosocomial Infections Study. Sections of lung tissue from 263 patients were submitted by 40 hospitals in 24 states. Legionnaires' disease was identified in 10 patients (3.8%) from six hospitals in five states. The clinical and epidemiologic characteristics of sporadic fatal nosocomial Legionnaires' disease were similar to those from cases that occurred during epidemics of Legionnaires' diseases. A case-control study showed that cases of Legionnaires' disease were associated with an increased occurrence of Legionnaires' disease during the period June through November, temperatures greater than 39.2 degrees C, and administration of corticosteroids before onset of pneumonia. Legionnaires' disease can occur as a fatal nosocomial pneumonia and has clinical and epidemiologic features that may be helpful in differentiating it from nosocomial pneumonia of other causes.


"Endotoxicity" of the Legionnaires' disease bacterium. The Legionnaires' disease (LD) bacterium is a gram-negative organism whose "endotoxicity" appears to differ in several respects from the classic endotoxicity generally associated with gram-negative bacteria. Discrepancies were noted between the high activity of LD bacteria in gelating limulus lysate in vitro and their low pyrogenicity in rabbits. Further in-vivo biologic tests indicated that LD bacteria were relatively weak in "endotoxicity". Analysis of LD bacterial cells and in their cellular fractions by gas-liquid chromatography indicated that LD bacteria did not contain hydroxy fatty acids commonly associated with lipid A of endotoxin. The branched-chain fatty acids that were characteristic of LD bacteria were associated with the cell envelope, and were readily extracted into organic solvents without prior saponification. The presence of 2-keto-3-deoxyoctonate in LD bacteria and cell extracts was detected by a microassay method but remains to be confirmed with gas-liquid chromatography and mass spectrometry. The active principle "endotoxicity" in LD bacteria may be a new type of bacterial lipopolysaccharide.


The cell envelope of the Legionnaires' disease bacterium. Morphologic and biochemical characteristics. We studied the cell-envelope structure of the Legionnaires' disease (LD) bacterium by electron microscopy and biochemical assays. There were apparent differences in cell structure by electron microscopy using two different prefixation methods. Organisms prefixed with gluteraldehyde had a single surrounding membrane. The typical two-membrane structure of gram-negative bacteria, however, was observed after prefixation with a combination of gluteraldehyde, formalin, and creosol. The cell wall (peptidoglycan) was seen in electron micrographs of plasmolyzed bacteria and in papain-digested cells. Both cytoplasmic and outer membranes were separated by differential centrifugation of spheroplast sonicates followed by sucrose density gradient ultracentrifugation. We identified each membrane by characteristic enzyme activity (cytoplasmic membrane) and 2-keto-3-deoxyoctonate content (outer membrane).


Cellular lipids of the Legionnaires' disease bacterium. We qualitatively and quantitatively analyzed the simple and complex lipids of 10 Legionnaires' disease bacteria. The phospholipids in decreasing order of concentration were phosphatidylcholine, phosphatidylethanolamine, cardiolipin, phosphatidylmonomethylethanolamine, phosphatidylglycerol, and phosphatidyldimethylethanolamine. The total phospholipids averaged 96 micromoles per gram dry cell weight. Phospholipid fatty acids were solely branched-chain fatty acids and were, in decreasing order of concentration, iso-C16:0, anteiso-C15:0, anteiso-C17:0, iso-C14:0, iso-C16:1, and an unidentified fatty acid. Neutral lipids identified were free fatty acid, ubiquinone, triglyceride, diglyceride, monoglyceride, and wax ester. Neutral lipid fatty acids consisted predominately of branched-chain fatty acids, normal fatty acids, and a minor unidentified fatty acid. Analysis of the cellular lipids of 10 Legionnaires' disease bacteria revealed an unusual and novel microorganism.


A high molecular weight antigen in Legionnaires' disease bacterium: isolation and partial characterization. We isolated a high molecular weight antigen of the Legionnaires' disease (LD) bacterium by column chromatography. The antigen was composed of 35% carbohydrate, 2.6% protein, 1.8% phospholipid, and 1% 2-keto-3-deoxyoctonate and was important in the host's antibody response because it inhibited the indirect immunofluorescent and microagglutination titers of convalescent sera from patients with Legionnaires' disease. The antigen also formed precipitin bands with seven of 10 convalescent sera from patients with Legionnaires' disease. We found chemical and biological evidence of endotoxinlike activity associated with the antigen. Cell sonicates and acid extracts of the LD bacterium gave multiple bands in immunodiffusion with human convalescent serum and rabbit antisera prepared against heat-killed LD bacteria. The antigenic structure of the LD bacterium therefore appears complex.


Surface topography and fine structure of the Legionnaires' disease bacterium. A study of six isolates from hospitalized patients. Six clinical isolates of the Legionnaires' disease bacterium have been isolated from patients in two Michigan hospitals. These organisms were recovered and cultivated in vitro and the strains named by city of recovery and order of isolation Detroit 1 to 4 and Flint 1 and 2. All strains, studied by scanning and transmission electron microscopy preparations from 7-day growth on agar, showed similar characteristics. By scanning electron microscopy the cells appeared bacillary, straight, and slightly curved, and spindle shapes and forms with rounded ends were observed. Detroit 2 and 3 and Flint 1 strains showed cells with ends having reduced diameters, the cells resembling an old-fashioned rolling pin. Cell widths ranged from 0.29 to 0.39 micron, and average lengths varied from 1.60 to 2.34 microns. Filamentous forms as long as 9.8 microns were observed. Surfaces appeared quite wrinkled compared to that of an Escherichia coli control organism. As seen by transmission electron microscopy, fine structure included a multilayered cell wall characteristic of gram-negative bacteria that was irregular, reflecting wrinkling; plasma membrane; and periplasmic space. Distinct nucleoid, intracytoplasmic ribosomes and rare vacuoles were also seen. No evidence of a spore or an adversity-resistant body was observed.


Classification of the Legionnaires' disease bacterium: Legionella pneumophila, genus novum, species nova, of the family Legionellaceae, familia nova. Deoxyribonucleic acid (DNA) relatedness was used to classify strains of the Legionnaires' disease (LD) bacterium. These DNA comparisons showed that all strains of the LD bacterium were members of the same species. Included were strains isolated from the environment and strains with three different O-antigens. The DNA from the LD bacterium was not significantly related to DNA from any other group of bacteria that was tested. Biochemical data, growth characteristics, and guanine-plus-cytosine ratios were used to rule out the possibility that the LD bacterium was significantly related to members of genera whose DNA was not tested. In view of these data we propose that the LD bacterium be named Legionella pneumophila species nova, the type species of Legionella, genus novum. The type strain of L. pneumophila is Philadelphia 1.


Survival of the Legionnaires' disease bacterium in water. Data from this study indicate that the Legionniares' disease bacterium can survive for a relatively long period of time in water. Four strains survived in distilled water for 69 to 139 d and for 364 to 369 d in tap water. Viable cells from two strains were recovered from tap water at 408 to 415 d. There were no surviving bacteria in cooling-tower water after 24 to 48 h. The rapid die-off was probably due to bactericidal agents added to the water to control growth.


Cooling towers and evaporative condensers. By 31 October 1978 there had been four confirmed instances where the Legionnaires' disease bacterium had been isolated from water samples taken from cooling towers or evaporative condensers located near the site of an epidemic of Legionnaires' disease. These devices are widely used to reject unwanted heat into the atmosphere and vary greatly in size and configuration. However, the operation of all towers and condensers depends on intimate contact between the circulating water and ambient air. Airborne contaminants in the vicinity of these devices are likely to be absorbed to some degree by the circulating water. The airstream leaving a cooling tower is saturated with water vapor and may also contain a relatively minute portion of the circulating water in the form of fine droplets known as drift. It is common practice to bleed a small portion of the circulating water, including all contaminants, from the tower into a storm sewer, sanitary sewer, or even a nearby body of water.


Immunologic protection against the Legionnaires' disease bacterium in the AKR/J mouse. Female AKR/J mice were challenged with the Washington strain of Legionnaires' disease (LD) bacteria. Nonimmunized mice inoculate intraperitoneally with 2 x 10(8) colony forming units became ill within 4 h and died within 24 h. Progressive histopathologic changes initiated as early as 2 h after inoculation involved the lymphoid organs, the crypts of the small intestine, and the liver. Necrosis with minimal inflammatory cell reaction was the primary lesion. Immunization with a soluble LD bacterial antigen failed to prevent illness but protected against death and development of abnormal histologic changes.


Immunoglobulin specificity of the microagglutination test for the Legionnaires' disease bacterium. Differences in results of microagglutination tests for the Legionnaires' disease bacterium on untreated sera and sera treated with 2-mercaptoethanol suggest that, like other agglutination tests, the microagglutination test is heavily dependent on the presence of IgM antibody.


Legionnaires' disease antigen detected by enzyme-linked immunosorbent assay. An enzyme-linked immunosorbent assay method has been developed for the rapid detection of antigen from clinical specimens such as urine and sputum. Preliminary evidence suggests that the antigen is present and can be detected in the sputum and possibly urine of patients with Legionnaires' disease. Patients not harboring the Legionnaires' disease bacterium have been uniformly negative to date.


Bystander-initiated cardiopulmonary resuscitation in the management of ventricular fibrillation. We assessed the influence of bystander-initiated cardiopulmonary resuscitation upon outcome in 316 consecutive patients treated for out-of-hospital ventricular fibrillation. Of 109 patients who received bystander-initiated cardiopulmonary resuscitation, 47 (43%) were ultimately discharged home. Of 207 patients for whom resuscitation was delayed until arrival of fire department personnel, 43 (21%) survived (P less than 0.001). Improved survival was largely due to a reduction in subsequent hospital mortality rather than to a higher rate of initially effective resuscitation. In a separate analysis of 118 patients treated at a single institution after resuscitation, the reduced hospital mortality reflected a decrease in deaths due to shock and to anoxic encephalopathy. In addition, neurologic dysfunction was significantly less common if bystanders had initiated cardiopulmonary resuscitation. Bystander participation in cardiopulmonary resuscitation represents an important adjunct to a rapid-response emergency care system.


Dementia, renal failure, and brain aluminum. Dialysis dementia is a progressive and usually fatal neurologic syndrome occurring in patients on chronic hemodialysis. These patients may also have elevated levels of aluminum (Al+3) in the cerebral cortex. Possible relations between brain Al+3, increased Al+3 intake, and dementia were evaluated. Studies were done in seven groups of patients and five groups of experimental animals. In both normal dogs and rats and those with renal failure, oral Al+3 loading (Al[OH]3), resulted in significant increases of brain Al+3 (P less than 0.01). In patients with renal failure, who were neither demented nor treated with dialysis, brain Al+3 was more than seven times normal (P less than 0.01), whereas in patients with dialysis dementia, mean brain Al+3 was more than 15 times normal. However, the two groups were not significantly different. Brain Al+3 was also significantly elevated in patients who had either metastatic cancer or hepatic coma. Apparently brain Al+3 can be elevated as a consequence of Al+3 loading, renal failure, and abnormalities of the blood-brain barrier. It is most likely that dialysis dementia has multifactoral causation and is probably not caused by elevated brain content of Al+3 alone.


Antecedent renal disease and the outcome of pregnancy. We assessed the effect of "healed" childhood renal disease on subsequent pregnancies by following-up a cohort of 224 children initially hospitalized with kidney disease. The pregnancy experience in this cohort was compared to two "control" cohorts comprising 81 female siblings and 191 age-matched female patients hospitalized contemporaneously for respiratory infection. The incidence of spontaneous abortion, stillbirth, and pregnancy-associated hypertension was not different among the cohorts; however, the incidence of infants with low birth weights was significantly greater in the renal and respiratory disease groups. Childhood kidney disease followed by impaired renal function (serum creatinine greater than 1.5 mg/dL) was associated with greater maternal and fetal morbidity. Kidney disease in childhood followed by apparent healing and no functional renal impairment does not have an adverse effect on maternal welfare, although the incidence of infants with low birth weight is apparently increased.


The natural history of urate overproduction in sickle cell anemia. Serum uric acid and uric acid excretion were studied in 95 patients with sickle cell anemia ranging in age from 17 months to 45 years to ascertain the natural history of urate overproduction. Hyperuricemia was infrequent in children with sickle cell anemia, but was found in 26 of 67 adults (39%). Thirty-six patients studied in a clinical research center had a mean urate clearance of 9.1 +/- 0.8 mL/min. Patients with sickle cell anemia were often normouricemic despite urate overproduction. Normouricemia was maintained by increased urate clearance, which was attributed to increased urate secretion. The hyperuricemic patients had decreased urate clearance with decreased pyrazinamide-suppressible urate clearance. Para-aminohippurate clearance was decreased to 634 mL/min in the hyperuricemic patients with sickle cell anemia compared with 853 mL/min in normouricemic hyperuricosuric subjects with sickle cell anemia. Hyperuricemia occurs only in patients who develop altered renal tubular function with diminished urate clearance secondary to diminished urate secretion.


Persistence of neutrophil hypersegmentation during recovery from megaloblastic granulopoiesis. We studied the rate of disappearance of neutrophil hypersegmentation in 23 patients with megaloblastic anemia during therapy with vitamin B12 and folic acid. In 14 patients with uncomplicated megaloblastic anemia, the neutrophil lobe average began to fall towards normal 11.4 +/- 0.3 (SEM) days after treatment was begun and became normal by 13.9 +/- 0.6 days. In nine patients with associated inflammatory disorders, the lobe average returned to normal more rapidly. In six initially neutropenic patients, a five-fold increase in total granulocyte count occurred by the eighth day and a seven-fold increment in the total number of circulating hypersegmented neutrophils. Granulocyte folate concentrations in five folate-deficient patients rose to normal levels within 4 to 7 days of starting therapy. Hypersegmentation thus persists for many days after correction of neutropenia and restoration of normal granulocyte folate levels have occurred. We conclude that cobalamin and folate are needed at two different steps in granulopoiesis.


Prolonged disease-free survival in Hodgkin's disease with MOPP reinduction after first relapse. Thirty-two patients with Hodgkin's disease who relapsed after a first complete remission induced by nitrogen mustard, vincristine, procarbazine, and prednisone (MOPP) were retreated with MOPP chemotherapy. Nineteen patients achieved a second complete remission. Median duration of the second complete remission was 21 months. The likelihood of achieving a second complete response could be predicted by the duration of the first response. Fourteen of 15 patients whose first complete remission was longer than 12 months achieved a second complete response in contrast to five of 17 patients whose initial complete remission lasted less than 12 months (P less than 0.001). Median survival of all patients in this study who were re-treated with MOPP was longer than 4 years after their first relapse. We conclude that patients with Hodgkin's disease who relapse after a first complete remission induced by MOPP are not necessarily resistant to further MOPP therapy and can achieve long-term survival with MOPP reinduction.


Primary pulmonary hypertension treated with oral phentolamine. A patient with symptomatic primary pulmonary artery hypertension underwent therapeutic trials with parenteral and oral phentolamine. Before drug therapy, he manifested marked increases in pulmonary artery pressure and pulmonary arteriolar resistance during exercise. This hypertensive response to exercise was significantly attenuated by parenteral phentolamine. He also manifested sustained hemodynamic improvement with the same degree of attenuation of exercise-induced increases in pulmonary artery pressure and pulmonary arteriolar resistance 7 months after initiation of therapy with oral phentolamine. Twenty months after initiation of therapy, the patient continues to enjoy symptomatic improvement with a marked increase in exercise tolerance.


Disseminated intravascular coagulation with the peritoneovenous shunt. Coagulation data were collected before and after peritoneovenous shunting for intractable ascites in 19 shunting procedures. After insertion of the shunts, changes consistent with disseminated intravascular coagulation developed in all cases in which good flow of ascitic fluid was obtained. In cases with temporary shunt function, the coagulation variables suggestive of disseminated intravascular coagulation returned toward normal when the flow of ascitic fluid ceased. A fall in the level of fibrinogen degradation products indicated that the shunt had clotted. Bleeding attributable to disseminated intravascular coagulation alone was uncommon. Clotting of the shunts was frequent. The use of heparin improved some of the coagulation variables but did not prevent shunt clotting or clinical bleeding. We conclude that the peritoneovenous shunt induces a moderate disseminated intravascular coagulation and that measurement of fibrinogen degradation products is useful in assessing shunt function.


Bone biopsy to diagnose hyperoxaluria in patients with renal failure. Primary hyperoxaluria is a rare congenital disorder characterized by large quantities of urinary oxalate with resultant nephrocalcinosis and nephrolithiasis and by deposits of calcium oxalate in other organs. Renal failure occurs early in life. Reports of unsuccessful renal transplantation attempts in this disorder underscore the need for antemortem diagnosis. Percutaneous bone biopsy is a relatively new procedure that is easily done at bedside, safe, and of potentially high yield in the demonstration of tissue oxalate. Three cases presented here show the characteristic histologic picture seen in this disease. In one case, the diagnosis was established by bone biopsy.


Solid tumors in multiple myeloma.

Solid tumors in multiple myeloma. The frequency of solid tumors was evaluated in 628 consecutive patients with multiple myeloma who had been treated with various melphalan-prednisone combinations. Among those patients who lived at least 2 months, the incidence and diversity of second tumors were similar to those in normal persons of the same age and duration at risk. The diagnosis was usually made within 2 years after the start of chemotherapy for the myeloma. Long-term melphalan therapy did not seem to contribute to the pathogenesis of second solid tumors in patients with multiple myeloma.


Indomethacin-induced prostaglandin inhibition with hyperkalemia. A reversible cause of hyporeninemic hypoaldosteronism. Hyporeninemic hypoaldosteronism was diagnosed in a young woman with glomerulonephritis who was receiving indomethacin therapy. Despite only mildly abnormal renal function, serum K+ was elevated to 6.2 meq/L, and plasma renin activity (0.12 ng/mL h) and aldosterone (4.4 ng/dL) failed to respond to the combined stimuli of furosemide and posture. Urinary prostaglandin E2 (PGE2) was suppressed (70 ng/24 h). When indomethacin was withdrawn, significant kaliuresis occurred, accompanied by normalization of serum K+ and PGE2 and a supranormal rebound in renin and aldosterone levels. Challenge with indomethacin resulted in antikaliuresis and resuppression of PGE2, renin, and aldosterone. This case study documents for the first time that indomethacin can cause the syndrome of hyporeninemic hypoaldosteronism, probably by inhibiting prostaglandin biosynthesis.


Single or combination therapy of staphylococcal endocarditis in intravenous drug abusers. Staphylococcus aureus is the commonest cause of acute endocarditis in intravenous drug abusers. In-vitro and in-vivo animal studies have found increased killing of organisms with the combination of a beta-lactam antibiotic and an aminoglycoside. These findings have created a controversy about the use of such combination therapy. We randomly treated 25 episodes of S. aureus endocarditis in intravenous drug abusers with either single or combination antibiotic regimens. Mean days to defervescence were similar in both groups: 6.3 d (SEM, 1.49 d) for the single drug group and 6.6 d (SEM, 1.02 d) for the group treated in combination with an aminoglycoside. There were no bacteriologic failures or relapses in either group. No patients needed valvular surgery, and the mortality rate was zero. Thus, it appears that single drug therapy with an appropriate beta-lactam antibiotic is adequate and appropriate in intravenous drug abusers with S. aureus endocarditis.


The use of thrombolytic agents: choice of patient, drug administration, laboratory monitoring. A proper choice of patient is critical in assuring both a satisfactory degree of lysis of the thrombus or embolus and a clinical course uncomplicated by serious hemorrhage. The best patients to treat are those who are seriously and acutely ill but without anatomic lesions that may bleed excessively. Thrombolytic agents can be administered by standard courses of therapy, and the monitoring of treatment with laboratory tests has been simplified and is concerned primarily with the documentation of a "lytic state."


Management of gout.

Management of gout. The diagnosis of gout depends on showing urate crystals in synovial effusions or, with less certainty, recognizing a characteristic clinical presentation. The management of gout has four phases: control of inflammation, diagnostic evaluation, education of the patient, and treatment for the hyperuricemia. Sound logical principles guide each aspect. Careful attention to these four phases of management should lead to highly satisfactory control of the syndrome of gout.


[Characteristics and complications of mediastinal brochogenic cysts. A report on five cases (author's transl)]. Five observations of mediastinal brochogenic cysts are used to illustrate the diagnostic and/or therapeutic difficulties encountered in cases with an ectopic topography or complications. In two cases, one of which was clearly located in the posterior mediastinum and associated with a false erosive appearance of the nearby vertebral body, it was possible to establish the degree of ectopic displacement of the bronchogenic cysts, and to comprehend the pre-operative diagnostic difficulties and nosological problems associated with these sequestrations. As far as complications are concerned, one observation was able to confirm that a sudden volume increase doesn't always correspond to a septic process, and that rapid secondary reduction in volume is not always accompanied by fistulation. Intracystic suppurations differ in appearance according to their location. In the subcarinal region they can cause a fistula, as in the case reported. In other regions, in this case the left lateral tracheal area, suppuration is enclosed, but it can be associated with suppurative lesions of the adjacent lung. The operative difficulties, partial cystectomy in one case and associated lobectomy in the other, are further evidence for the need for systematic excision of all bronchogenic cysts as soon as they are diagnosed and before complications occur.


[Pseudotumoral rheumatoid coxitis (author's transl)]. Two cases of rheumatoid coxitis of the macrogeodic type are reported. In one case, there was a very large anfractuous cavity in the socket and head, complicated by a pathological fracture of the socket, which raised the suspicion of a malignant tumor. The authors review the characteristics of these macrogeodic forms of rheumatoid arthritis, about forty cases having been reported in the published literature.


[Abnormalities of fibrin formation in benign viral hepatitis (author's transl)]. Abnormalities of fibrin formation were studied in 42 young adult patients with benign viral hepatitis. It was observed that there was a constant increase in thrombin time and reptilase time, evoking an abnormality of the second stage of fibrin formation, or the aggregation of fibrin monomers. This abnormality is not associated with the presence of inhibitors in the patients' serums, and is maximum at an alkaline pH. The hypothesis of an abnormality of the fibrinogen molecule, a dysfibrinogenemia, is the most likely cause, and this has to be confirmed by biochemical and immunochemical studies.


[Symptomatology in 162 patients with spasmophilia (chronic idiopathic or constitutional tetany). A statistical analysis using a computer (author's transl)]. A computer was used for a statistical analysis of the results of treatment in 162 patients (130 women and 32 men with an average age of 29 years), with chronic idiopathic tetany. Symptoms leading to diagnosis were mainly feelings of ill-health (27.2 %), motor disorders (19.7 %), and sensory problems (19.1 %). The onset of acute attacks is related, more especially, to psychogenic factors. The frequency of the various clinical manifestations, and their symptomatic grouping were analyzed. The clinical profile is similar in both sexes apart from 7 of the 89 items: lipothymia, abnormal feelings of warmth, pseudo-contraction of the larynx, abnormalities of the exoskeleton, and digestive disorders are more frequent in women, while precordalgia is more often present in men. Factorial analysis of correspondence between 38 variables reveals a very large dispersion of the variables, as the first three factors, which are the most significant, supply only 30% of the total information. Furthermore, very few variables share significant relationships in each factor. In spite of the amount of information collected, this dispersion of the symptomatology does not permit the definition of one or more profile-types of spasmophilia.


[Thrombosis of the portal and superior mesenteric veins in a patient with a congenital and familial deficiency in antithrombin III (author's transl)]. Thrombosis of the visceral veins is an extremely rare condition in cases of congenital and hereditary deficiency of antithrombin III, associated with recurring venous thorbosis of the limbs. The authors report such a case in a man of 40 years of age, who had this deficiency, associated with thrombosis of the portal and superior mesenteric veins and a portal cavernoma. They stress the frequent association of recurring peripheral vein thrombosis, portal vein thrombosis in adults, and thrombosis of the mesenteric vein, and the importance of systematic measurements of antithrombin III levels in these pathological conditions.


[Sarcoma of the right superior pulmonary vein: physiopathological study of the progressive stenosis in a lobar vein (author's transl)]. A part from the interest aroused by the exceptional nature of this case of sarcoma of the right superior pulmonary vein, it enabled definition of the angiographic appearances of the affection of the vein. Physiopathological examinations, including vascular redistribution, development of a systemic collateral circulation, and the reflux of hematosed blood into the pulmonary trunk, were able to establish the diagnosis in vivo.


[Epidemiology of asbestos-induced mesotheliomas in inhabitants of the Saint-Etienne area. Apropos of 35 cases]. The 35 cases reviewed in this study provided evidence that apart from occupational dust hazards there could be a risk of asbestos dust contamination which is not related to working conditions but occurs through urban and industrial pollution.


[Scapular and vertebral osteopathies during acute myoclonic bismuth encephalopathies. Apropos of 8 cases]. Among 59 cases of bismuth encephalopathy, 8 patients were observed to have osteo-articular lesions of the shoulders and dorsal vertebral. These included osteonecrosis of the head of the humerus, which has been reported previously, uni- or bi-lateral fractures of the upper end of the humerus, and vertebral fractures. Severe and repeated myoclonic spasms appear to be capable of causing fractures; microscopic fractures in the spongy bone could explain the osteonecrotic images observed.


[Circulatory and respiratory effects of aspiration and reinfusion of ascites in cirrhosis. Apropos of 14 ascitic attacks treated by this method]. Aspiration and replacement of ascites in 14 patients with cirrhosis was carried out using a Rhodiascit (Rhône-Poulenc) apparatus. Hemodynamic studies were used to evaluate the effects of this therapy on circulatory and respiratory parameters. Results showed that the hemodynamic tolerance of the treatment, which produces a slow increase in blood volume, was excellent as there was an increase in the cardiac index without raising the pressure under which replacement was made. Futhermore, no adverse effects on blood respiratory functions were noted in these patients who had blood hypoxia before treatment, but the removal of ascitic fluid produced no improvement in arterial gasometric parameters which is contrary to what one would expect.


[Chronic gastritis and intestinal metaplasia (author's transl)]. The diagnosis of chronic gastritis can be made from the macroscopic lesions seen on endoscopy, and the severity of the changes noted in the mucosa after biopsy under direct vision. Gastric intubation can also be used to confirm the pathological results. If the atrophied mucosa shows highly differentiated diffuse intestinal metaplasia, the examinations should be repeated at regular intervals, as they could herald the onset of malignant changes. The authors discovered 312 cases of intestinal metaplasia in 4 920 patients who had been gastroscoped in the Digestive Endoscopy Center of François-Moutier. A total of 157 of them, were noted to have very highly differentiated diffuse lesions, and 54 of these cases had at least yearly repeat gastroscopies. A diagnosis of intrinsic cancer was made in four patients, and this was confirmed by taking serial sections of the specimens removed.


[Paravertebral hematopoietic pseudotumor during Paget's disease (author's transl)]. Extramedullary hematopoiesis is usually secondary to a severe and prolonged reduction in medullary functions, but can be the rare consequence of an extrusion of tissue formed of weakened or fractured bone. The hematopoietic nature of this pseudotumor can be confirmed histologically or, as in this case of Paget's disease, by Indium scintigraphy which can define the specific locations of the hematopoietic marrow.


[Physiopathology of osteoporosis (author's transl)]. Osteoporosis is the result of the progressive loss of bone substance which occurs during a lifetime. Its histomorphological characteristics have been well-defined and it appears to be a single entity more particularly related to the general problem of cellular senescence. The rate at which bone is lost can be influenced by many events or general factors, known or unknown, which are capable of accelerating or slowing down its progression. The period when the fracture threshold is passed appears to depend on a bone mass which is weak at the end of the growth period, followed by genetic, mechanical--related more specifically to insufficient muscular activity--, hormonal-hypo-oestrogenemia-factors, and pathological episodes of more rapid demineralization (immobilization, corticotherapy) which become more irreversible with advancing age.


[Diagnosis of primary osteoporosis (author's transl)]. The diagnosis of osteoporosis is usually based on the presence of hypertransparent radiological images of the spinal column with vertebral collapse, when other relatively rare causes (mainly myeloma) have been excluded. One recognized, other etiological factors have to be discarded, especially cortisone therapy, before diagnosing primary osteoporosis in patients over 55 years of age in whom it is more frequently present in women (post-menopausal osteoporosis). Various indices of the amount of bone present in the limbs and pelvis can be used to assess the proportion lost with age, but these give only incomplete information on the degree of vertebral osteoporosis.


[Loss of bone with advancing age (author's transl)]. Loss of bone with advancing age can be evaluated by different methods: tomography, measuring the metacarpal corticomedullary index by monochromatic photonic bone absorptiometry, or by the bone-calcium mass as measured by neutronic activation in vivo. Analogous results are given by all these methods: there is reduction in the total bone mass after fifty years or so in women, and after about sixty years in men. The authors discuss the physiopathology of the osteopenia with increasing age, and more particularly the role of oestrogen-deprivation after the menopause.


[Oestrogen therapy of osteoporosis (author's transl)]. Twenty women with physiological (11) or post-operative (9) lack of oestrogen and progesterone developed progressively painful decalcifying osteosis. Improvement was obtained (after eliminating all contra-indications) by treatment with an oestrogen (17-bêta oestradiol-14 times) associated with a progesterone (14 times ) and increased calcium and phosphates (11 times). Clinical improvement was still present after a period varying from 6 to 36 months, with disappearance of the pain symptoms in 7 cases, and very great improvement in 9 cases. After 6 months of treatment there was also a significant reduction in the biological signs of bone resorption (blood phosphorus levels, calcium-creatinine ratio in morning urine specimens taken after fasting, total calcium in a 24-hour urine specimen). The improvement noted, both clinically and biologically, confirms the effect of oestrogens in reducing bone resorption, underlines their preventive and also curative action, and makes them suitable for use in decalcifying osteosis due to hormone lack, after eliminating all contra-indications and under strict regular supervision (breasts and endometrium).


[The treatment of osteoporosis (author's transl)]. Treatment for osteoporosis cannot yet be prescribed in a perfectly rational manner, as the total picture of the pathogenesis of this disease remains uncertain. Furthermore, lack of significant criteria makes it difficult to evaluate the different therapeutic methods proposed, and none of them appears to be entirely satisfactory. By acting methodically, however, one can obtain good relief of pain, quiescent osteoporotic activity over long periods, and bone remineralization. At the present time, preference has to be given to standard medications such as calcium, phosphorus, and anabolic proteins which are nearly always given in association. Calcium inhibits osteolysis by slowing down parathyroid secretion. Phosphorus accelerates calcium fixation in bone and appears to stimulate the formation of osteoblasts. Anabolic compounds protect the bone-forming framework and assist the deposition of mineral salts in the bones. The prescription of vitamin D is of value when there is a deficiency. Among recent medications which have been tried, only calcitonin appears to be of some practical value, by assisting inhibition of certain flare-ups and lytic episodes of the osteoporosis when associated with standard therapy.


[Idiopathic arteriovenous fistula of the renal peduncle (author's transl)]. Idiopathic arteriovenous fistulae in the renal peduncle are rare. A case was discovered during clinical examination, and was confirmed by total and selective arteriography. A vertebral and dise infection of L3-L4 was also present and blood cultures were positive for enterococcus. This fistula had a high blood-flow rate but it has to be stressed that it was well-tolerated by the cardiovascular system. It was also exceptional in that conservative therapy was possible in this case, which is the eighth reported up to the present time.


[Systemic allergic vasculopathy after naproxen (author's transl)]. The authors report a case of hypersensitivity angiitis presenting with cutaneous, muscular, articular, and renal signs. They suggest a possible etiological mechanism for such disorders: a circulating immune-complex disease, and criticize the often improper interpretation of the results of lymphoblast transformation tests. Hypersensitivity angiitis, "ground base disease", requires investigation for possible underlying immunity abnormalities or neoplasms.


[The association of a myeloma and Paget's disease (author's transl)]. The coexistence of a myeloma and Paget's disease in the same patient is only rarely reported in the published literature. The frequency of such an association was studied when reviewing 3 cases observed by the authors: an IgG myeloma discovered following a spasmodic paraplegia in a patient with Paget's disease; a patient who was found to have a myeloma, a polynuclear neutrophil leukemia, and Paget's disease; and an IgG myeloma in a patient with probable localized Paget's disease. The incidence of the association myeloma-Paget's disease is much lower than that of sarcomatous degeneration. It should be determined precisely, however, as our future conception of the reciprocal relationship between the two diseases is greatly dependent on this information. Furthermore, the very few cases reported, and their lack of homogenicity, are the reasons why most authors feel that the association of myeloma and Paget's disease as pure coincidence. Many new cases, however, have been recently reported. The problem of the significance of the association of Paget's disease and macroglobulinemia or other monoclonal gammapathies has still to be solved.


[Cerebral manifestations of sarcoidosis (author's transl)]. Sarcoidosis lesions in the brain are relatively rare and can remain latent, or become evident in various forms: meningitic, encephalitic, neuro-endocrinian, vascular, or tumoral. A case is reported of an Antilles patient aged 35 years, in whom the diagnosis was made by examination of an operation specimen, following the discovery of an apparently isolated intracranial hypertension.


[The provoked-hyperglycemia test. Follow-up after two years of 94 cases with doubtful results (author's transl)]. A retrospective study of 94 patients, who had had doubtful results in the oral provoked-hyperglycemia test, was made after an average period of 23 months. It was found that 26 patients were diabetic, 34 were normal and 34 were still doubtful. The factors which influence the evolution of these cases are the sex, a family history of diabetes (before 60 years of age), and the return to normal weight of obese patients.


Frontal sinus mucocele.

Frontal sinus mucocele. Although not uncommon, and certainly not rare, frontal sinus mucocele was seen in 4 cases by the authors. Since one of the cases was rather unusual, we were prompted to evaluate the subject and prepare this manuscript. Gradual onset of unilateral proptosis should make one suspicious of a mucocele involving the paranasal sinuses, the frontal and ethmoid being the 2 most common locations. Diplopia, due to limited ocular motility on upward gaze, along with proptosis and epiphora are frequently the presenting symptoms which, in one particular case, paradoxically improved at first with topical anti-inflammatory therapy . A team approach (ophthalmologist, radiologist, otorhinolaryngologist, and neurosurgeon) are essential for an accurate diagnosis and therapeutic approach to this problem. The use of a precut template from the Caldwell projection is a very useful device to outline the contours of the frontal sinus during surgery. The not-so-frequent use of abdominal fat to fill the frontal sinus cavity is presented with no apparent postoperative fat necrosis. A 5-year follow-up has shown the patient to be free of recurrences.


Malignant melanoma of choroid in a case of nevus of Ota. A white woman with unilateral nevus of Ota presented with visual loss and an intraocular mass resembling a choroidal melanoma. Indirect ophthalmoscopy, fluorescein angiography, ultrasonography, and radioactive phosphorus uptake corroborated the clinical impression and surgery was advised. Following enucleation, the specimen was examined with light microscopy, which revealed a mixed cell type malignant melanoma of the choroid. Electron microscopy disclosed the presence of premelanosomes in the episclera, indicating that the episcleral pigmentation is a result of melanocytic evolution. This paper represents the tenth report in the literature of choroidal melanoma occurring in a patient with nevus of Ota, and the first electron-microscopic study of an eye with this association of lesions.


Prognosis for the evolution of Ophthalmology: Part II. This paper represents an application of modern forecasting methods to prognosis in ophthalmology. Using these methods the author considers possible changes in patterns of ocular pathology in the next 20 to 25 years. He also indicates the probable evolution of such methods of investigation as biomicroscopy, ophthalmoscopy, electrophysiology, and automatic diagnosis. In the field of ophthalmosurgery, the author explores the idea of automation of eye surgery and extended use of micromanipulators in surgery. He predicts the autoplasty of the anterior segment and the transplant of the whole eye.


Biopsy-negative cranial arteritis with complete oculomotor nerve palsy. Cranial arteritis (CA) presenting as sudden blindness is well documented, and early recognition of this entity in an elderly patient with visual loss or diplopia is of critical importance. This entity presents a difficult diagnostic problem when temporal artery biopsy is negative, as in our case, or when the erythrocyte sedimentation rate is normal. The present report details an unusual patient with "occult temporal arteritis" who sustained abrupt monocular visual loss and subsequent ipsilateral ophthalmoplegia involving all functions of the oculomotor nerve. Despite negative biopsies of each temporal artery, other probable etiologies of the symptom complex were excluded, and the diagnosis of cranial arteritis is warranted. The patient is unique in that the oculomotor palsy is complete and permanent. This report emphasizes cranial arteritis masquerading as an intracranial aneurysm.


Use of computerized axial tomography (CAT scan) in evaluating therapy of orbital pseudotumor. Two patients with orbital pseudotumor, demonstrated by computerized axial tomography (CAT scan), are presented. This radiological technique was further used to demonstrate the complete resolution (Case 1) and marked regression (Case 2) of the orbital masses after steroid therapy. CAT scan characteristics of orbital pseudotumor were discussed and contrasted with the findings in thyroid ophthalmopathy. It is our recommendation that patients with CAT scan and clinical characteristics of orbital pseudotumor should be treated with systemic steroids and resolution of the inflammatory lesion should be corroborated by a repeat scan in atypical cases. Orbital surgery and other invasive studies should be used in those patients in whom there is no objective improvement in the disease process.


Water drinking provocative test.

Water drinking provocative test. Water drinking provocative test was carried out in 28 chronic simple glaucoma and 17 borderline cases of chronic simple glaucoma. These tests were carried out twice on the same patients with an empty stomach and after taking breakfast at an interval of 15 days. It was observed that there was no significant difference in the outcome of the results even when this test was carried out with a full stomach.


The fluorescein appearance test for lacrimal obstruction. The fluorescein appearance test has been developed for the evaluation of the patency of the lacrimal excretory system. This objective test is simple, painless, physiologic, and reliable. The only materials required are 2% fluorescein, ultraviolet light, and a tongue blade. A 2% fluorescein solution is instilled in the conjunctival cul-de-sac after which the posterior oropharynx and nostrilis are examined with ultraviolet light. Over 90% of 92 eyes from 66 normal subjects gave positive results within 30 minutes and 100% gave positive results within 60 minutes. Slow appearance times can be anticipated because there appears to be a correlation between Schirmer test values and the time required for a positive fluorescein appearance test. The test proved clinically useful in evaluating patients with epiphora and in making the diagnosis of several cases of lacrimal obstruction verified by nuclear dacryocystography.


Supernumerary lacrimal canaliculi.

Supernumerary lacrimal canaliculi. Supernumerary extopic canaliculi in a 12-year-old white male patient are presented. Their external openings (puncti) were located on the lateral surface of the nose, 1 cm from the inner canthus, and were reaching the lacrimal sac directly. The anomaly was surgically corrected and 2 years after the operation the patient is free of symptoms.


Evaluation of an improved suture for cataract surgery. An improved synthetic absorbable suture for ophthalmic surgery, 8-0 Dexon "S" polyglycolic acid, was evaluated in 25 cataract extractions and, in 5 cases, compared with 8-0 Vicryl polyglactin sutures. Dexon "S" sutures caused less tissue drag than Vicryl sutures; Vicryl was more easily knotted. With respect to handling, knotting, tissue drag, absorption, and postoperative complications, the improved Dexon suture was found to be well suited for use in cataract surgery.


Factors influencing prognosis in indirect traumatic rupture of the globe. Fifty indirect traumatic ruptures of the globe were reviewed in order to isolate factors important in determining the visual outcome: (1) The presence of a hyphema at the initial examination is a very bad prognostic sign. (2) A small rupture carries a better prognosis than a large rupture (arbitrary dividing line, 9 mm). (3) Cryotherapy or diatherapy used at the wound edge at the time of surgical repair improves prognosis.


Investigative approaches to the problem of pancreatic cancer. A prospective study of 134 patients suspected of having pancreatic cancer is reported. Ultrasonography and duodenal drainage studies are the best initial investigations. Endoscopic retrograde cholangiopancreatography with cytological examination is the test most likely to provide a definitive diagnosis. Arteriography is essential before laparotomy to delineate anomalies in the foregut vasculature. Pancreatic oncofetal antigen is the only tumour marker that is useful in diagnosis and in monitoring therapy.


The radiological assessment of ectopic lower third molars. Experiments using observers ranging in experience from undergraduates to consultants showed that the orthopantomograph can be used satisfactorily to predict the time taken to remove those ectopic lower third molars capable of being put into Winter's classification. When used for this purpose this radiograph compared well with the lateral oblique view of the mandible. There were differences with the intraoral view, but it could not be certain which was superior. The value of the orthopantomogram in predicting impaired postoperative labial sensation was tested. It became apparent that there were cases in which the nerve was clearly at risk and others in which it was clearly not at risk. Variations in the anatomy of the canal and the quality of its image could give rise to doubt, some of which could be resolved by taking intraoral views. An unsuccessful attempt using analysis of multiple regression was made to select and quantify those features of the radiograph important for predicting the time taken for removal of the teeth. A simple points scoring method was evolved which agreed with current practice and was capable of being used effectively by undergraduates, some of whom had made inadequate assessments hitherto.


The lymphatics of the prostate gland and their role in the spread of prostatic carcinoma. The results of research are reported which provide conclusive evidence of the presence of functioning intraprostatic lymphatics. The hypothesis that the prostate is an 'immunologically privileged site' devoid of demonstrable intraprostatic lymphatics is no longer valid. Intraglandular metastases via the intraprostatic lymphatics might be responsible for the multifocal presentation in prostatic carcinoma. Lymphatic spread is a primary event in a significant number of cases. The conventional separation of modes of spread as haematogenous and lymphatic seems artificial and physiologically unsound, as tumour cells tend to recycle from one system to another. The application of clinical prostatolymphography as a diagnostic tool in N-staging and as a potential therapeutic adjunct, using a suitable radioisotope, in the management of prostatic carcinoma has to be assessed.


Inaugural Sidney Werner Lecture. The surgical treatment of thyroid disease in modern perspective. It is timely to review the place of surgery in the treatment of thyroid disease when for some years endocrinologists, pharmacologists, and radiotherapists have made most of the running. This account falls naturally into three parts, simple, malignant, and toxic goitre.


A simple clinical approach to quantifying losses from the extracellular and plasma compartments. It is possible to estimate the category and volume of lost liquid in patients who have become acutely depleted of body fluids by measuring the haematocrit and plasma protein concentration in venous blood samples. Three recent examples of different categories of loss are presented: plasma loss in pancreatitis, extracellular fluid (saline) loss in paralytic ileus, and mixed plasma and extracellular fluid loss in peritonitis complicating acute appendicitis. Goood clinical results were achieved by infusion of appropriate volumes of either plasma or saline so as to restore the haematocrit and plasma protein concentration to their presumptive basal values.


Extended deep femoral angioplasty and lumbar sympathectomy as a limb salvage procedure. Limb salvage in 27 limbs (26 patients) using the combined operations of extended deep femoral angioplasty and lumbar sympathectomy is described. A successful result was obtained in 14 cases (52%) at 6 months falling to 12 (45%) at 16 months. Prediction of outcome and postoperative progress was monitored by the measurement of the leg: arm pressure ratio using the Doppler ultrasound apparatus. No patient with a preoperative ratio of less than 0.3 had a successful result. It is proposed that lumbar sympathectomy is a logical adjunct to surgery in these patients in order to enhance the development of the collateral circulation.


A biological survey of a Cambridge suburb: assortative marriage for IQ and personality traits. An account is given of a study, carried out in a Cambridge suburb, which measured the similarity in IQ and some personality traits between spouses. In both sexes mean IQ scores tended to diminish from social class I to V. Lower IQ scores were associated with higher levels of extraversion, neuroticism and inconsistency. Assortative marriage was found for IQ components, Total IQ, extraversion-introversion and inconsistency scores. Both geographical and social stratification were shown to affect the degree of assortative marriage.


Matrimonial distance, inbreeding coefficient and population size: Dhangar data. Data on the distance between the birthplaces of spouses (matrimonial distance) were collected from 2,260 married individuals belonging to 21 endogamous castes of the Dhangar (shepherd) cast-cluster of Maharashtra, India. The general form of the distribution of matrimonial distances is one which is extremely positively skewed and leptokurtic. The percentage of intra-village marriages generally decreases from the southern areas of Maharashtra to the northern areas of the state, as does the inbreeding coefficient. This situation is in conformity with the socio-cultural norms regulating matrimonial choice in south and north India. An attempt has been made to relate the degree of inbreeding to the mean matrimonial distance and population size. The mean matrimonial distance is more useful in predicting the degree of inbreeding than population size.


Biological variations associated with change in lifestyle among the pastoral and nomadic tribes of East Africa. The values of a number of anthropometric, cardiovascular and biochemical variables have been compared between tribal and non-tribal Samburu. Significant differences between the two groups were found for ponderal index, supra-iliac and mid-calf skinfold thicknesses, pulse rate and both systolic and diastolic blood pressures. Similar analyses were performed on samples from tribal and non-tribal Maasai; here significant differences were found for ponderal index, height, biceps skinfold thickness, pulse rate and systolic blood pressure. No significant differences were found in serum cholesterol or serum triglyceride for either the Samburu or the Maasai. Greater variability of the skinfold measurements was found in the non-tribal Samburu than in the tribal group; this effect was less marked in the Maasai. A principal component analysis and three discriminant function analyses were performed on the Samburu data. These analyses showed that the most marked difference between the tribal and non-tribal groups was in their blood pressure levels, the non-tribal sample having significantly higher mean values than the tribal members. Possible causes for the observed differences between tribal and non-tribal groups are discussed, and the findings are contrasted with those of an earlier study, in which significant differences in cholesterol but not in blood pressure were found between samples of rural and urban Maasai. This leads to the tentative hypothesis that blood pressure is affected immediately by the change in environment, whereas the effect on cholesterol levels is a longer-term one.


Genetic heterogeneity within an electrophoretic phenotype of phosphoglucose isomerase in a Japanese population. The thermostability of the five kinds of electrophoretically variant phenotypes of GPI which were found in Japanese in a previous study (Tanis et al. 1977) was examined. The most frequently found variant phenotype, termed GPI 1-4HIR1, observed in 20 individuals could be divided into three distinct classes on the basis of thermostability characteristics. These classes were termed 'stable', 'labile', and 'very labile'. 'Stable' lost approximately 20 and 60% of its original activity after heating 10 and 30 min at 52-5 degrees C, respectively, while normal GPI lost approximately 30 and 70% of its original activity. 'Labile' lost approximately 40 and 80%, and 'very labile' lost approximately 55 and 90% of its original activity under the same heating conditions. Electrophoresis showed that that thermostability was a characteristic of the variant protein molecule but not of the electrophoretically normal molecule. The order of the stability of these three kinds of variants against 5 M urea was the same as that of their thermostability. No difference against inhibition by 6-phosphogluconate was observed among the normal and the variant phosphoglucose isomerases. Family studies confirmed the genetic nature of the thermo- and urea stability differences among the affected individuals.


Intestinal lactase status of adults in Papua New Guinea. Fifty hospital patients in Port Moresby (mean age 30 yr) without evidence of malnutrition or gastro-intestinal disease, who came from many parts of Papua New Guinea (P.N.G.), were given 50 g lactose orally after an overnight fast. In 49 blood glucose rise was less than 1.1 mmol 1(-1), indicating hypolactasia. Thirty-three gave a clear history of symptoms, usually diarrhoea, after lactose. Adult hypolactasia approaches 100% in P.N.G. There is no indication that the genetic structure of any part of the population of P,N.G. with regard to lactase has been influenced by genetic drift from peoples with persistence of lactase into adult life (PL).


Finger ridge-count variability in sub-Saharan Africa. Mean finger ridge-count data were obtained, primarily from literature sources, for 31 male and 24 female sub-Saharan African samples. The 10 finger ridge-counts and total ridge-count were used as independent variables in a multiple regression analysis, latitude and longitude serving in turn as the dependent variables. The results show that it is not the magnitude of the ridge-counts themselves that is important, but rather contrasts between groups of digits. The most important geographically patterned variation in ridge-counts consists of contrasts between digits 4 and 5 and digits 2 and 3. South and south-east African populations are characterized by low contrasts, west Africans by high contrasts and, south-west Africans are intermediate. The geographical patterning of the contrast agrees well with known patterns of gene flow into and within the continent as determined by serological genes. Principal components analysis was also carried out to determine whether within-group components corresponding to the geographically relevant between-group variation could be identified. The third, fourth and fifth components drew the same types of contrasts between the groups of digits identified in the multiple regression analysis, but they were relatively unimportant. The geographically important principal components would have been overlooked in a traditional multivariate analysis of finge ridge-counts, since the analysis would have been dominated by pattern size. We conclude that finger ridge-counts are potentially very useful in population studies, but account must be taken of their multicomponent nature.


A comparison of the biochemical properties of the human diaphorase (DIA3) isozymes determined by the common alleles DIA13, DIA23 and DIA33. (1) Various buffer systems for the starch gel electrophoresis of human diaphorase isozymes have been explored. Electrophoresis in a Tris/Borate system at pH 8.6 which includes 70 micron NADH in the gel and cathodal electrode buffers, provides good resolution of the six DIA3 phenotypes previously resolved by isoelectric focusing. (2) The variant genes DIA13, DIA23 and DIA33 occur with frequencies of about 0.76, 0.23 and 0.01 respectively in the English population. (3) The isozymes determined by the least common gene, DIA33, are markedly different from the isozymes determined by DIA13 and DIA23 in their relatively low heat stability, high affinity for Blue Sepharose and slow anodal electrophoretic mobility in buffer systems containing borate. The DIA3 1 and DIA3 2 isozymes are similar to one another in these characteristics.


The pattern of facial growth before and during puberty, as shown by French-Canadian girls. The results are reported for an analysis of longitudinal sequences of lateral head X-rays of 50 Montreal girls, taken annually between the ages of 6 and 15 years. Mean size changes for distances within the cranial base, the maxilla and the mandible, as well as those outlining the facial polygon, are displayed on a common proportional scale based on mean sizes at 15 years old. Mean growth velocities are displayed on both a chronological age scale and on one relative to the individual age of peak growth velocity in stature. A distinct facial pattern of growth is established, In terms of the proportion of final size achieved during childhood, it is below the cranial pattern, but above the general skeletal one. This facial pattern shows a pubertal peak in growth, but one quantitatively less important than that for stature. The timing of the two peaks is closely aligned, although the evidence favours a slightly later development for the face. The mandibular ramus provided the sole exception to this common facial pattern, though some questions on maxillary growth remain open.


The genetic determination of fumarase isozymes in human tissues. (1) A method for the starch gel electrophoresis of human fumarase has been devised which resolves two groups of isozymes: one group (FHM) is associated with the mitochondria, the other (FHS) is cytosolic. (2) Tissue to tissue variation in the complexity of the isozyme patterns and the examination of red cells fractionated according to their age by density gradient centrifugation suggest that the least anodal isozymes of the FHS group and ofthe FHM group are modified in vivo with the generation of several secondary isozymes. (3) Red cells, which display only FHS isozymes, were screened from 776 European and 100 Nigerian individuals and a single electrophoretic variant (phenotype FH 2-1) was identified in a middle-aged male from England. The same variant was identified in a paternal aunt and the data suggest that the variant repressents heterozygosity for the common (FH1) allele and a rare variant (FH2) allele at an autosomal locus. (4) Fibroblasts and white cells from the FH 2-1 individual showed variation in the FHM and FHS isozymes indicating that the mitochondrial and the soluble forms of fumarase are determined at the same structural locus.


Human Y chromosome variation in normal and abnormal babies and their fathers. C-banded chromosome preparations were obtained from cord blood from normal newborns and venous blood from abnormal newborns and the corresponding fathers. There is significant heterogeneity between individuals in euchromatin and especially heterochromatin lengths of the Y chromosome. The average dimensions of the Y of fathers of normal and abnormal babies do not differ. Y chromosomes from cord blood appear more condensed than from venous blood and the consequences are not removed by the use of the Y/F index. Such differences have not been considered in reported apparent variation in the size of the Y chromsome in relation to criminality.


The genetics of palmar creases. A study in the inheritance of liability estimated from the incidence among relatives. Six-hundred and fifty-nine Chinese children and 613 first degree relatives were studied with regard to four variations in the palmar creases: the simian crease, the Sydney line, the radial border termination of the thenar crease, and the distal border termination of the distal crease. With the exception of the Sydney line, these palmar crease variations were found to occur with significantly increased frequency in the parents of the propositi compared with 400 controls, indicating the presence of genetic factors in their embryogenesis. If the polygenic hypothesis is accepted, the very high heritability of liability (100%) to the radial border termination of the thenar crease is a further demonstration of the importance of the genetic contribution. Variations in the palmar creases thus cannot be totally explained away by early flexional folding in the skin of the developing hand.


Hair colour in the Faroe and Orkney Islands. Hair samples from 274 Faroe Islanders (mean age 16.7 years) and 246 Orkney Islanders (mean age 13.5 years) were classified and divided into eight colour categories by matching them to standard samples on the "Haarfarbentafel nach Fischer-Saller". Sex differences in the proportions in each category in both the Faroese (144 males, 130 females) and Orcadians (120 males, 126 females) were tested by x(2) and were not significant. A highly significant difference (1% level) was found in the proportions in the eight categories between the total Faroese and Orcadian samples. The Faroese subjects, despite their higher mean age, have a higher proportion of light-haired individuals. Hair of a "smoky-grey" tone, clearly unrelated to greying with age, and not represented on the Fischer-Saller scale, is reported and was found to be predominantly a feature of Orcadian males. The results for the Faroe and Orkney Islanders are compared with data for other North Atlantic populations.


Association of weights of some organs during the prenatal period. The change of proportion of organ weights for the liver, intestines, lung, kidney, thymus, heart and spleen were analysed for 33 Japanese fetuses (sexes combined) by multivariate allometry. The thymus showed the highest allometric coefficient, and the spleen the next highest. The intestines, heart, liver, kidney showed medium coefficients, and the lung had the lowest.


Sex differences and bilateral asymmetry in dermatoglyphic pattern elements on the fingertips. In the present paper, 539 Polish families and 999 individuals (515 males and 484 females) were analysed to determine whether asymmetry of dermatoglyphic patter elements on the fingertips of ulnar and radial loops in genetically controlled. And we enquire whether the body is bilaterally asymmetrical. We have found the asymmetry between right and left hand fingertips for ulnar and radial loops, for each digit and between the two sexes. The differences between the sexes is small. The bimanual difference in dermatoglyphic pattern elements between hands, right minus left, has been used as a measure of asymmetry. The mean and variance difference for males is not significantly different from the mean and variance for females. An investigation was also made of correlations between relatives for bimanual differences, right minus left. We may conclude from these results that the asymmetry of dermatoglphic pattern elements on fingertips of ulnar and radial loops has little hereditary component. Finally, the results of this work show that the dermatoglyphic pattern elements on fingertips of ulnar and radial loops on each side of the body are inherited.


Gene frequency and fitness change in an age-structured population. Fisher's system of reproductive value weighting, whereby each age group is assigned a weight purported to measure its contribution to the ancestry of future generations, was suggested by him as a way of ironing out irregularities in the change of population numbers when the age structure is not in equilibrium. This has been extended to Mendelian populations for two models. In Model I, the reproductive value of each genotype is computed from a table of age-specific survival and reproduction rates, and the genic values are computed by averaging these genotypic values. The total reproductive value of an allele and of the population always increase at a rate equal to the reproductive value-weighted average fitness regardless of age structure. This has the disadvantage that the total reproductive value is not equal to the census numbers, when age-stability has been reached. In Model II, this difficulty is surmounted, but the formula is no longer exact. The reproductive value of an allele for a specific age x is measured from the average death and reproductive rates of individuals of age x carrying that allele. An expression is given for the rate of change of reproductive value of an allele or of the population. In many circumstances this changes nearly uniformly, regardless of irregularities of age structure, and goes over to the census numbers as age stability is approached. The special difficulties in populations with separate sexes are discussed and a formula for rate of change of mean reproductive value, analogous to Fisher's Fundamental Theorem of Natural Selection, is given.


The use of multiple thresholds and segregation analysis in analyzing the phenotypic heterogeneity of multifactorial traits. (1) Three models based on multifactorial inheritance are introduced to account for phenotypic heterogeneities. These models are used to determine whether subforms of a triat are: (a) different degrees of the same process, (b) non-familial environmental variants of the same process, and (c) independently transmitted processes. (2) The parameters of each model consist of two population prevalences and either one, two, or three correlation coefficients which reflect the three hypotheses given above. The models are formulated so that a likelihood ratio test may be performed to discriminate between them. (3) The following types of analyses are described: (a) analysis of prevalence data with separate population prevalence estimates, (b) analysis of prevalence data with the proband a parent with specified spouse, (c) analysis of prevalence data with the proband an offspring with specified parents, and (d) the full segregation distribution of families using Complex Segregation Analysis. (4) When compared with the Analysis of Prevalences, Complex Segregation Analysis has the following advantages: (a) the number of degrees of freedom for parameter estimates is greater and separate estimates of the population prevalences are not necessary, (b) standard errors of the parameters are smaller, and (c) the power to discriminate models is increased. (5) Phenotypic heterogeneities such as age of onset, severity, and sex effect can be more completely understood by the methods of analyses described above. The nosology of familial disorders can also be clarified, and environments relevant to the transmission of the trait can be detected. This approach is particularly suitable for the analysis for behavioural traits since it does not require the assumption that environmental effects common to relatives be ignored. (6) Finally, our experience indicates that incorporating both prevalence and pedigree data into a single analysis decreases the time required to perform the analysis.


The effects of demographic transition on the opportunity for selection: changes during the last century in Italy. The index of opportunity for selection proposed by Crow has been calculated for the Italian population during the last century. The evolution of its two components, the pre-reproductive mortality and the variance in fertility, has been also analysed and compared with similar data for the United States. The results clearly show the relevance of socio-economic changes to the evolution of selective patterns in our species; in particular the relative incidence of mortality and fertility to selection intensity: the total index has in fact been reduced by 75% during the last century, the relative amount due to fertility increasing from 57 to 89%. The probable different relevance of genetic factors in the two components has also been discussed.


Trends in human reproductive wastage in relation to long-term practice of inbreeding. The trends in reproductive performance and wastage are studied in relation to consanguinity of marriage and age of women on a population sample of 20,626 women, from the rural and urban areas of North Arcot District in South India. Data were collected by qualified women investigators using intensive interveiw techniques and specially developed questionnaires. Adequate quality control mechanisms were set up to ensure reliability of information gathered. For each marriage, a family pedigree was drawn extending upwards to two early generations on the side of each spouse in order to determine the existence and type of consanguinity married, 80% or more of such between an uncle and a niece or between first cousins. Altogher 70 161 total pregnancies were recorded for the 20,626 women. The differences between consanguineous and non-consanguineous marriages in terms of total foetal loss, perinatal, neonatal, postneonatl and infant mortality rates showed only marginal differences that attain statistical significance only because of the large sample size involved. No consistent relationships were observed between the degree of consanguinity and these reproductive losses. These actual differences were more marked in the older age-groups of women and declined to rather insignificant proportions as the age groups became younger. Taking into consideration the various socio-demographic factors, the narrowing differentials in the reproductive wastage between consanguineous and non-consanguineous marriages from the oldest to the youngest women confirm the tapering effects of continued inbreeding practices on the reproductive wastage. Further studies on these lines are still in progress.


[Effects of mycobacterial hydrosoluble adjuvants on the induction and prevention of experimental autoimmune uveo-retinitis in guinea-pigs (author's transl)]. Experimental uveo-retinitis (EAU) was induced in guinea-pigs after one systemic injection of retinal extract mixed with the hydrosoluble adjuvants (WSA) or muramyl dipeptide (MDP). In this model, 50 micrograms of WSA in incomplete Freund's adjuvant had the same adjuvanticity as 50 micrograms mycobacteria. The MDP, tested at low doses (2 to 100 micrograms), was less effective. But MDP, even in aqueous solution without oil, stimulated the induction of a tolerance to the retinal antigen: with addition of MDP, only one injection of the antigenic preparation was sufficient to delay and clearly reduce the development of EAU induced by the antigen plus complete Freund's adjuvant two and a half months later.


Improved lymphocyte ectoenzyme function during normal pregnancy. During normal pregnancy, the 5'-nucleotidase (AMPase) enzyme activity on the circulating human lymphocyte pellet has been found to be increased significantly (p less than 0.001) in comparison with that of healthy normal persons employed as controls. The increased lymphocyte activity diminished rapidly subsequent to parturition. The enzyme activity on lymphocytes purified from umbilical cord blood was not increased. Acute viral infections induced a transient reduction in the enzyme activity. Further studies of this natural defence mechanism are in progress.


[Correlation of skin test to grass pollen with basophil degranulation test results in 72 patients (author's transl)]. Seventy-two subjects have been tested by skin-test (ST) and human basophil degranulation test (HBDT) with grass pollen extract (GPE). HBDT was done, using a suspension enriched in basophils, by a technic on slide. Results are expressed by an index (DI) which is percentage of basophils having apparently disappeared (i. e. degranulated) in presence of GPE. No less than 100 intact basophils (and often many more) were always counted in absence of GPE (control) for each subject, so that DI higher than 35% are significant (p less than 0,001). DI were higher than 35% in 28 positive ST subjects for at less one of three dilutions of GPE (10(-4), 10(-6), 10(-8)); in the 5 subjects with false-negative result, 3 had a weak ST response. In 39 subjects with negative ST, DI were higher than 35% in two subjects and only for one dilution (10(-4)). So, concordance of results of HBDT and obviously positive ST reaches 94%. In 33 positive ST subjects, a significant correlation appears between DI (at 10(-4) and 10(-6)) and flare diameter and between DI (at 10(-4)) and wheals diameter. HBDT appears to be a suitable and simple technic for routinely study of reaginic allergies.


[Comparative study of immunopathogenic ability of autologous and allogeneic spermatozoa in Hartley guinea-pigs (author's transl)]. Autologous or allogeneic spermatozoa in amounts of 10(8), 10(7), 10(6) or 10(5) incorporated in complete Freund's adjuvant were injected into hemiorchidectomized Hartley guinea-pigs. The course of autoimmune aspermatogenic orchi-epididymitis, delayed hypersensitivity and humoral responses to autologous and allogeneic spermatozoa and to spermatozoa autoantigens S, P and T (isolated from a large pool of spermatozoa) were investigated after 1,2,3 or 4 weeks of evolution. Testicular and epididymal lesions and the cellular and humoral responses to autoantigens S and T were nearly identical in autoimmunized and alloimmunized guinea-pigs; but the delayed hypersensitivity responses to whole spermatozoa was more frequent in alloimmunized than in autoimmunized guinea-pigs. This latter result might not be due to the addition of two responses on to autoantigens and one to alloantigens (both present in allogeneic spermatozoa) since the positive responses of the alloimmunized guinea-pigs to autologous spermatozoa compared to allogeneic were found more frequent. From the technical conditions of the experiments, especially due to the use of complete Freund's adjuvant, a helper effect originating in allotypic determinants on allogeneic spermatozoa seems an unlikely explanation. Autoimmunization or alloimmunization in incomplete Freund's adjuvant instead of complete adjuvant provoked a weak response. However, the antibody response to antigen S was significantly more frequent in alloimmunized than in autoimmunized animals; in this case allotypic determinants in autoantigen S responsible for a helper effect might be the cause.


[Characteristics of the antibiotic sensitivity of nitrofuran--resistant Gram-negative bacteria of clinical origin]. 494 persons with various purulent inflammatory diseases were examined. Gram-negative nitrofuran resistant organisms isolated from the clinical material were found in 22.9 per cent of the cases. Representatives of Enterobacteriaceae, Klebsiella-Enterobacter-Serratia (26.8 per cent), Proteus-Providencia (16.8 per cent) and E. coli-Arizona-Citrobacter (16.1 per cent) predominated. Pseudomonas (32.1 per cent) and Acinetobacter (5.3 per cent) predominated among the aerobic gram-negative bacteria. Sensitivity of 131 strains to 10 chemotherapeutic drugs was determined. 60.4 per cent of the aerobic and 44.2 per cent of the Coli bacteria had multiple drug resistance (to 5 and more drugs). The organisms isolated from the urine and wound excretion were most resistant. Representatives of Pseudomonas and Klebsiella-Enterobacter predominated among the polyresistant cultures. High sensitivity of the isolates to gentamicin, carbenicillin and nalidixic acid was noted.


[Comparative study of the distribution of semisynthetic cephalosporins in the body of rats]. Distribution of 6 cephalosporin antibiotics, i. e. cephaloridin, cephalotin, cephradin cephacetryl, cephazolin and cephapyrin for parenteral use was studied comparatively on rats. The studies showed that all the above cephalosporins were well absorbed into the blood after intramuscular administration. The highest serum levels were achieved with the use of cephozolin. Still, its levels in the animal organs were mainly not higher and sometimes even lower than those provided by the other antibiotics. The highest levels of cephalosporins were detected in the kidneys. Cephalotin, cephapyrin and cephacetryl differed by the character of their distribution in the rats from the other 3 antibiotics: the levels of cephalotin and cephapyrin in the heart, spleen and muscles were lower than those of the other cephalosporins; sometimes they were even not detected in these organs; cephacetryl was not found in these organs. The levels of these 3 antibiotics in the kidneys were lower than those of the other cephalosporins. Cephalotin, cephacetryl and sometimes cephapyrin were not detected in the rat liver. None of the cephalosporins was found in the brain tissue.


[Pathomorphological picture of the liver in mice administered antitumor antibiotics intraperitoneally and its comparative assessment]. A single administration of carminomycin, ribomycin or olivomycin in LD50 or treatment of the experimental animals with these antibiotics for 10 days in the therapeutic doses equal to 10 per cent of the LD50 induced distrophic and necrobiotic changes in the liver. The use of bruneomycin in the equivalent doses induced sclerotic process in addition to the above doses resulted in a decrease in the colour intensity of DNA, RNA and protein as compared to the control, the content of glycogen and a marked increase in the amount of lipids in the hepatocyte cytoplasm. The most pronounced shifts were observed with the use of carminomycin, rubomycin and especially bruneomycin in single doses. With the use of olivomycin in a single dose the shifts were less pronounced. It should be noted that with the use of carminomycin and rubomycin the damages were of the same character by their intensity. The changes in the liver on the use of carminomycin, rubomycin and olivomycin in single doses or during the treatment course were reversible, while on the use of bruneomycin they preserved to the end of the experiment.


[Protein-nitrogen metabolism in the liver of rats intraperitoneally administered carminomycin]. It was found in the experiments with rats that in response to carminomycin administration in a single LD50 and the therapeutic doses during the treatment course the intracellular fond of the amino acids in the liver tissue increased, the autolytic processes activated, the activity of the transamination enzymes, histidine and ammonia lyases increased. The level of the residual nitrogen increased mainly at the expense of increased ammonia production and urea levels. These changes were more pronounced when the antibiotic was administered in LD50. Independent of the administration multiplicity and the antibiotic dosage they were of reversible nature and mainly disappeared by the end of the observation.


[Role of antibiotics in the ecology of actinomycetes]. The organisms producing ristomycin, rifamycin, lincomycin, tobramycin, rubomycin carminomycin, olivomycin, bleomycin and actinomycin D were practically not sensitive to their own antibiotics in the concentrations close to those produced during the biosynthetic process. At the same time other actinomycetous species close to the above organisms were suppressed to a significant extent by their antibiotics in the same concentrations. The experimental data indicated that the antibiotics had a protective effect on the organisms producing them and played a significant role in ecology of the actinomycetes.


[Synthesis and properties of the 14-amino derivatives of daunorubicin and carminomycin]. Interaction of 14-bromine derivatives of daunorubicin and carminomycin, as well as their aglycones with secondary amines, such as piperidine, N-methylpiperazine and morpholine was studied with a purpose of preparing new potentially antitumor antibiotics. It was found that reaction in acetone or dioxan at a temperature of 50--60 degrees C resulted in formation of 14-amino derivatives of the respective bromides. 14-Piperidinyl- and 14-(N-methylpiperazinyl)-daunorubicin, 14-piperidinyl-daunorubicinon and 14-piperidinyl-carminomycinon were prepared. The structure of the new substances was confirmed by the IR, UV and NMR spectra. The antimicrobial activity of 14-amino derivatives amounted to 10--35 per cent of the activity of the initial antibiotics, i.e. daunorubicin and carminomycin.


Microbial methanogenesis and acetate metabolism in a meromictic lake. Methanogenesis and the anaerobic metabolism of acetate were examined in the sediment and water column of Knaack Lake, a small biogenic meromictic lake located in central Wisconsin. The lake was sharply stratified during the summer and was anaerobic below a depth of 3 m. Large concentrations (4,000 mumol/liter) of dissolved methane were detected in the bottom waters. A methane concentration maximum occurred at 4 m above the sediment. The production of (14)CH(4) from (14)C-labeled HCOOH, HCO(3) (-), and CH(3)OH and [2-(14)C]acetate demonstrated microbial methanogenesis in the water column of the lake. The maximum rate of methanogenesis calculated from reduction of H(14)CO(3) (-) by endogenous electron donors in the surface sediment (depth, 22 m) was 7.6 nmol/h per 10 ml and in the water column (depth, 21 m) was 0.6 nmol/h per 10 ml. The methyl group of acetate was simultaneously metabolized to CH(4) and CO(2) in the anaerobic portions of the lake. Acetate oxidation was greatest in surface waters and decreased with water depth. Acetate was metabolized primarily to methane in the sediments and water immediately above the sediment. Sulfide inhibition studies and temperature activity profiles demonstrated that acetate metabolism was performed by several microbial populations. Sulfide additions (less than 5 mug/ml) to water from 21.5 m stimulated methanogenesis from acetate, but inhibited CO(2) production. Sulfate addition (1 mM) had no significant effect on acetate metabolism in water from 21.5 m, whereas nitrate additions (10 to 14,000 mug/liter) completely inhibited methanogenesis and stimulated CO(2) formation.


Evaluation of microbial flora of the eye during wear of soft contact lenses. The microflora of the eye has been monitored in 21 patients during a 6-month period to study changes resulting from wear of soft contact lenses. A minimum of 20 cul-de-sac cultures were taken from each patient. Fifty-one percent of cultures taken prior to lens wear were positive for microbial growth, whereas, after lens wear, positive cultures ranged from 14.3% to 30.9" over the 6-month period. Staphylococcus epidermidis was the most frequently isolated organism, followed by Micrococcus spp., diphtheroids, and Bacillus spp. Nonfermentative, gram-negative rods and fungi were isolated spordically. Bacterial growth was sparse from all specimens, but individual differences were found. The microflora of the eye appears to resemble that of the skin, suggesting that the eye has no real flora of its own, but has a transient flora supplied from the skin, possibly the eyelid.


Anaerobic metabolism of immediate methane precursors in Lake Mendota. Lake Mendota sediments and the immediate overlying water column were studied to better understand the metabolism of the methanogenic precursors H2/CO2 and acetate in nature. The pool size of acetate (3.5 microns M) was very small, and the acetate turnover time (0.22h) was very rapid. The dissolved inorganic carbon pool was shown to be large (6.4 to 8.3 mM), and the turnover time was slow (111 H.). CO2 was shown to account for 41 +/- 5.5% of the methane produced in sediment.  Acetate and H2/CO2 were simultaneously converted to CH4. The addition of H2 to sediments resulted in an increase specific activity of CH4 from H(14)CO3- and a decrease in specific activity of CH4 from [2-14C]acetate. Acetate addition resulted in a decrease in specific activity of CH4 from H(14)CO3-. The metabolism of H(14)CO3- or [2-14C]acetate to 14CH4 was not inhibited by addition of acetate or H2. After greater than 99% of added [2-14C]acetate had been turned over, 42% of the label was recovered as 14CH4 20% was recovered as 14CO2 and 38% was incorporated into sediment. Inhibitor studies of [2-14C]acetate metabolism in sediments demonstrated that CHCl3 completely inhibited CH4 formation, but not CO2 production. Air and nitrate addition inhibited CH4 formation and stimulated CO2 production, whereas fluoroacetate addition totally inhibited acetate metabolism. The oxidation of [2-14C]acetate to 14CO2 was shown to decrease with time when sediment was incubated before the addition of label, suggesting depletion of low levels of an endogenous sediment electron acceptor. Acetate metabolism varied seasonally and was related to the concentration of sulfate in the lake and interstitial water. Methanogenesis occurred in the sediment and in the water immediately overlying the sediment during period of lake stratification and several centimeters below the sediment-water interface during lake turnovers. These data indicate that methanogenesis in Lake Mendota sediments was limited by "immediate" methane precursor availability (i.e., acetate and H2), by competition for these substrates by nonmethanogens, and by seasonal variations which altered sediment and water chemistry.