Exploring the use of death certificates as a component of an occupational health surveillance system.

An effort has been made to explore a case-finding surveillance system for occupationally-related disease using death records. A sentinel health event, here lung cancer in young males, was selected to seek unusual associations with occupations as listed on the death records. Fishermen appeared to be over-represented and population studies cited suggest lung cancer in this occupation deserves further exploration. Further efforts of this type could test the usefulness of an occupational health surveillance system based on the death certificate.


Rheumatic fever in Minnesota. II. Evaluation of hospitalized patients and utilization of a State Rheumatic Fever Registry.

We studied the hospital records of 124 patients with a discharge diagnosis of acute rheumatic fever who were hospitalized in 21 Minneapolis-St. Paul hospitals during 1975 and 1976. After careful review of the hospital records, we found that 83 (67 per cent) of these patients did not have an acute illness. Seventeen (41 per cent) of the 41 cases with an acute illness were thought to adequately fulfill the Jones' Criteria for acute rheumatic fever. Upon review of the rheumatic fever registry of the Minnesota State Health Department, we found that less than one-half of the hospitalized patients had been reported to the registry. Cases that fulfilled and did not fulfill the Jones' Criteria were reported with equal frequency, indicating significant underreporting and overreporting of rheumatic fever. Evaluation of secondary rheumatic fever prophylaxis, both in those patients with acute rheumatic fever as well as in those with rheumatic heart disease, indicated that many patients who, in theory, should be receiving prophylaxis were not receiving it. These studies indicate a need for more thorough evaluation of the current epidemiology of rheumatic fever and the role of a rheumatic fever registry, and imply a need for reevaluation of these programs. (Am J Public Health 69:767-771, 1979).


Ischaemic heart disease mortality and the business cycle in Australia.

Trends in Australian heart disease mortality were assessed for association with the business cycle. Correlation models of mortality and unemployment series were used to test for association. An indicator series of "national stress" was developed. The three series were analyzed in path models to quantify the links between unemployment, national stress, and heart disease. Ischemic heart disease (IHD) mortality and national stress were found to follow the business cycle. The two periods of accelerating IHD mortality coincided with economic recession. The proposed "wave hypothesis" links the trend in IHD mortality to the high unemployment of severe recession. The mortality trend describes a typical epidemic parabolic path from the Great Depression to 1975, with a smaller parabolic trend at the 1961 recession. These findings appear consistent with the hypothesis that heart disease is, to some degree, a point source epidemic arising with periods of severe economic recession. Forecasts under the hypothesis indicate a turning point in the mortality trend between 1976 and 1978. (Am J Public Health 69:772-781, 1979).


Health costs of economic expansion: the case of manufacturing accident injuries.

The hypothesized relationship between economic expansion and accident injuries is tested using archival economic and accident data from the Los Angeles-Long Beach, California metropolitan area. The association is measured using cross-correlation techniques after variation shared with a comparison metropolitan area (Anaheim-Santa Ana-Garden Grove) is removed. Two tests of association are conducted. The first uses the raw accident rate of the comparison metropolitan area as a control variable while the second adjusts the control variable to reflect shared industrial sectors. Findings suggest that the incidence of disabling accidents increases in the month before and during the month that the manufacturing work force expands. The impact appears strongest during the month that new workers are added.


The effects of changes in smoking habits on coronary heart disease mortality.

Coronary heart disease (CHD) mortality declined by about 20 per cent between 1965 and 1976. During the same period there were substantial decreases in the proportion of adults who smoked based on data from the National Health Interview Survey (HIS). This study examines the extent to which changes in smoking can account for the decrease in CHD mortality for men and women aged 35-64 years. By applying US smoking levels (estimated from HIS) to data from four epidemiologic studies on the relative risk of CHD death by amount smoked, we obtain estimates of the portion of the decline in CHD mortality attributable to changes in smoking. Smoking changes among women were not generally consistent with declines in CHD mortality. For men, the estimated impact of smoking on CHD mortality varied considerably depending upon which study was used to estimate the relative risk by amount smoked.


Evaluation of a group nutrition education approach to effective weight loss and control.

Fifty-three male officers of the Boston Police Department voluntarily participated in a 12-week nutrition program with weight control as a primary goal, and education in related health factors as a secondary goal. One year after graduation, 26 respondents to a survey reported losing an average additional 0.5 kg since graduation for a mean weight loss of 11.4 kg since their introduction into the classes. None had returned to their original weight status.


Self care for colds: a cost-effective alternative to upper respiratory infection management.

A Cold Self-Care (CSC) Center was established in a prepaid ambulatory care setting serving 21,500 subscribers and their dependents. After CSC establishment, a decrease in visits to practitioners for common colds was demonstrated. The operating cost ratio of an outpatient visit as compared to a CSC visit was 14.7/1. Savings over a two-year period are estimated at over $46,000, representing an average estimated ratio of $.09 cost per dollar saved per member per year.


Waterborne giardiasis in the United States: a review.

Twenty-three waterborne outbreaks of giardiasis have been reported in the US, 1972-77. Data indicate that disinfection as the only treatment for surface water sources is ineffective in preventing waterborne transmission of this organism. To protect against transmission, all surface water should receive chemical pretreatment, preferably with sedimentation, and filtration in addition to disinfection. Outbreak data indicate that negative coliform tests do not provide assurance that water is free of Giardia cysts.


Successful treatment of symptomatic Entamoeba polecki infection.

The second symptomatic case of Entamoeba polecki infection, the first to respond to therapy, is reported. The patient experienced intermittent episodes of abdominal cramps, diarrhea, nausea, and malaise associated with large numbers of E. polecki cysts in the stool. Following treatment with diloxanide furoate and metronidazole, all symptoms cleared and the parasite was no longer present in the stool.


Host-parasite relationship in schistosomiasis mansoni in the mutation diabetic mouse (db/db).

Impairment of cell-mediated immunity has been described in chemically-induced as well as mutation diabetes in the mouse. The present report examines the host-parasite relationship during the acute phase of schistosomiasis mansoni in the mutation diabetic mouse (db/db). Cercarial penetration and maturation and egg output by adult worms were similar in the db/db mice and their littermate controls (db/+). In contrast, the pathological consequences of schistosomiasis were much less in the db/db mice. The mean liver weight computed as a percentage of body weight in db/db mice was 4.6 +/- 0.2 and following 8 weeks of infection it was 5.7 +/- 0.3 (difference is not statistically significant), whereas in infected db/+ mice it was 7.2 +/- 0.5. Infection in db/+ mice increased their mean portal pressure by 124% in contrast to an increase of only 12% in db/db animals. The most striking difference was noted in the mean granuloma diameter in the liver: 402 +/- 35 micrometer in db/+ in comparison to 147 +/- 10 micrometer in db/db mice (P less than 0.001). This study demonstrates the crucial role of the host granulomatous response in the causation of disease due to Schistosoma mansoni. Furthermore, it underlines the decreased pathological consequences when the host granulomatous response is suppressed, which can be compared to the response of modulated animals with chronic schistosomiasis.


Correlation of Culex tarsalis population indices with the incidence of St. Louis encephalitis and western equine encephalomyelitis in California.

Mosquito population indices from California for the period 1953-1973 were analyzed to determine their association with activity of St. Louis encephalitis (SLE) and western equine encephalomyelitis (WEE) viruses. Culex tarsalis female populations, as measured by New Jersey light trap indices (LTI), correlated positively with the incidence rates of encephalitis in humans, and were a reliable means of forecasting the years of highest incidence. The critical level of C. tarsalis in urban areas below which no human cases of SLE and WEE were detected was an LTI of 0.1. Critical urban levels of C. tarsalis associated with significant human SLE or WEE incidence ranged between LTIs of 6.4 (for rural mosquito abatement districts [MADs] with large resident human populations). Peaks in annual incidence of SLE and WEE in humans occurred during years when seasonal average C. tarsalis female populations in urban areas reached a LTI of 21. Peaks in weekly incidence of SLE and WEE were associated, respectively, with weekly LTIs of 21 and 81 in urban traps. Isolation rates of SLE virus from mosquito pools and transmission of the virus to enzootic hosts were highest when urban LTIs were between 10 and 19.9 and between 5 and 9.9, respectively. The WEE viral isolations and enzootic transmission rates were highest when LTIs in urban areas were 1-4.9.


Experimental infection of vertebrates of the Pocomoke Cypress Swamp, Maryland with Keystone and Jamestown Canyon viruses.

Experimental studies were conducted to assess the susceptibility of white-tailed deer (Odocoileus virginianus), gray squirrels (Sciurus carolinensis), and cottontail rabbits (Sylvilagus floridanus) to Jamestown Canyon (JC) and/or Keystone (KEY) virus infection. Viremia occurred in 5 of 6 deer inoculated with JC virus; however, all deer developed KEY virus neutralizing antibody. Based on the observation that antibody elicited by primary infection of deer with either KEY or JC virus exhibited partial heterologous neutralization in vitro, cross-challenge experiments were performed in these animals. Keystone virus failed to infect deer 30 days post primary JC virus infection; however, deer became infected when challenged with KEY virus 80 days after the initial JC virus infection as indicated by a substantial increase in antibody titer. Similarly, JC virus failed to produce viremia in immune animals infected with KEY virus 80 days previously, although 2 of the 3 animals challenged had serological evidence of infection. Three field-collected cottontail rabbits with no evidence of KEY antibody were readily susceptible to KEY virus infection and developed viremias of 1-4 days' duration; rabbits with KEY virus antibody did not develop viremia upon KEY virus challenge. Eight antibody-negative field-collected gray squirrels became viremic following injection with KEY virus; however, a comparable group of squirrels did not become viremic when injected with JC virus.


Geographic distribution of arbovirus antibodies in indigenous human populations in the Indo-Australian archipelago.

Sera from lifetime residents in 16 localities of the Indo-Australian archipelago and adjacent areas were tested for hemagglutination-inhibition antibody against four alpha-viruses (Sindbis, Getah, chikungunya, and Ross River) and for neutralizing antibody against six flaviviruses (dengue 2 and 3, Japanese encephalitis, Murray Valley encephalitis, Kunjin, and Edge Hill). Mosquito collections were carried out in some of the localities to study vector relationships to distribution of the arbovirus antibodies. Antibodies specific to Sindbis and Getah viruses were rare except in north Australia. Chikungunya virus-specific antibody was highly prevalent in localities of the Oriental zoogeographic region and Wallacea, rare in west New Guinea, and absent in north Australia. Age distribution of chikungunya antibody suggested that the antibody last occurred in most Indonesian localities about 30 years ago. Ross River virus-specific antibody was confined to localities of the Australian zoogeographic region. Antibodies reacting to dengue 2 and 3 viruses occurred in high frequency in the entire area of the archipelago. Antibodies specific to Murray Valley encephalitis and Kunjin viruses were also widespread although at a very low frequency. Japanese encephalitis virus-specific antibody was highly prevalent in areas west of Wallace's Line while it was absent in areas east of the line with the exception of Lombok. Antibody to Edge Hill virus was rare and confined to the Australian zoogeographic region. The distribution of arthropod vectors, vertebrate hosts, and of arboviruses are discussed in relation to zoogeographic divisions.


A comparison of La Crosse virus isolated obtained from different ecological niches and an analysis of the structural components of California encephalitis serogroup viruses and other bunyaviruses.

Analyses of the oligonucleotide fingerprints of the three genome ribonucleic acid (RNA) species of 11 isolates of La Crosse (LAC) virus, obtained from various ecological niches in the northern United States and compared to those of prototype LAC virus, showed that in each place from which these isolates were obtained LAC variants and varieties were present with related, but distinguishable, nucleotide sequences for their large, medium, or small RNA species. The RNA genomes of prototypes trivittatus (TVT), snowshoe hare (SSH), Tahyna (TAH), and Lumbo (a variety of TAH) viruses of the California encephalitis (CE) serogroup, and Guaroa of the Bunyamwera serogroup also consist of three RNA species, each with unique and distinguishable nucleotide sequences which bear little resemblance to those of the LAC virus isolates. The virions of CE group viruses (CE, Jamestown Canyon, Keystone, LAC, Melao, SSH, TVT, TAH viruses and South River, an unregistered virus) have three major viral polypeptides, designated G1, G2, and N.


The investigation of related cases for the control of diarrhea in cities in developing countries.

An example of how follow-up of related cases of diarrhea by epidemiologically-oriented health promoters can result in important public health measures is described. The follow-up of related cases involved a search for an outbreak in which a population with a high attack rate could be defined in order to increase the likelihood of a successful investigation by means of a cross-sectional retrospective study design. Then, through standard epidemiologic techniques, the risk factors to be studied were selected and a questionnaire was designed and executed. The results of this investigation demonstrate that greater meticulousness in pursuing epidemiologic principles is required for success in diarrhea outbreak investigations in developing countries than in developed countries despite the fact that controllable contaminations discoverable by these techniques are much more frequent in the former. In the present investigation it was found that flavored drinks packaged in plastic by a process assuming increasing importance in food distribution were causing diarrhea because of unhygienic manufacturing procedures. A concomitant bacteriologic study helped confirm the epidemiologic findings, and bacteriologic cultures at different points in the manufacturing process suggested a solution to the contamination problem found.


Intensive care unit treatment of acute renal failure following snake bite.

Twenty-nine patients with acute renal failure following bites by snakes of the genera Crotalus and Bothrops were treated in an Intensive Care Unit (ICU). Eight were given conservative treatment. Peritoneal dialysis was necessary in 21 patients, and hemodialysis in one of these. The main complications occurring while the patients were in the ICU were pulmonary edema (5 cases), respiratory failure (4), cardiac arrest (4), and hypovolemic shock (1 case). Three patients died with respiratory and hemodynamic disturbances while in the ICU, one of them during the polyuric phase. Twenty-four patients were discharged from the hospital with no clinical or laboratory evidence of renal failure. Two patients developed bilateral cortical necrosis of the kidney. One of them died in the general ward after interruption of dialysis and the other was discharged from the hospital with chronic renal failure. It was not possible to perform a kidney transplantation. The importance of the ICU in the recovery of such patients is stressed.


The effect of trimethoprim and sulfamethoxazole on Toxoplasma gondii in vitro and in vivo.

Trimethoprim (TMP) and sulfamethoxazole (SMZ) were studied alone and in combination to determine their effect in vitro on intracellular Toxoplasma gondii and in vivo against murine toxoplasmosis. In the in vitro experiments, whereas 1 and 2 microgram/ml TMP had no demonstrable effect on intracellular T. gondii, 10-20 microgram/ml TMP resulted in death of the intracellular organisms; concentrations as high as 100 microgram/ml SMZ had no demonstrable effect against the intracellular organisms. When used in combination, a significant synergistic effect was noted with 2 microgram/ml TMP-50 microgram/ml SMZ. Studies on the kinetics of inhibition and/or killing of Toxoplasma revealed that 18 hours of treatment with 2 microgram/ml TMP-50 microgram/ml SMZ resulted in irreversible inhibition of the intracellular organisms. When used in vivo against a 50,000 LD100 dose of Toxoplasma, TMP fed by gavage or mixed in the diet had no effect in murine toxoplasmosis at doses as high as 200 mg/kg a day. SMZ administered by gavage had no effect at doses up to 200 mg/kg a day; but at 300 and 400 mg/kg SMZ, protection was 47% and 83%, respectively. Treatment of infected mice was continued for 14 consecutive days, whether the drugs were administered alone or in combination. The combination 200 mg/kg TMP-200 mg/kg SMZ, when administered by gavage, protected 87% of mice. Survival after 14 days of SMZ mixed in the diet was 0% at 100 mg/kg, 47% at 200 mg/kg, and 100% at 300 mg/kg. Survival with the combination was 40% for 200 mg/kg TMP-100 mg/kg SMZ and 100% for 100 mg/kg TMP-200 mg/kg SMZ. The half-life of TMP in serum of Swiss Webster mice was calculated to be 24 min. The results obtained in vivo were inferior to those obtainable with the combination of pyrimethamine plus sulfadiazine. The problems of interpretation of results obtained in the murine model using TMP-SMZ and in their extrapolation to the treatment of the infection in man are discussed.


Onchocerciasis focus in Colombia: follow-up study after 12 years.

This study is a follow-up of a 1965 investigation of the only known focus of Onchocerca volvulus in Colombia. In the first phase of the current study, 254 persons were examined. Of the 19 individuals found to be infected with O. volvulus, the youngest was a 16-year-old male. Among those included in the 1965 study, 22 were examined again for microfilariae. Two were positive in both studies, 4 were positive in 1965 but negative in 1977 and the remaining 16 were negative on both occasions. The prevalence of infection, based on identification of microfilariae in skin snips, was lower in the current study (7.5%) than the 15.1% recorded 12 years earlier. However, a 50% response to the Mazzotti test (administration of oral diethylcarbamazine) among a limited number of people upstream from the previously identified endemic area suggests that infection with O. volvulus may be quite widespread.


Development of Onchocerca volvulus in Simulium ochraceum and Simulium metallicum.

The development of Onchocerca volvulus was compared in Simulium ochraceum and S. metallicum by maintaining infected flies under uniform conditions. Larval development in S. ochraceum was synchronous and orderly so that nearly all larvae reaching the thoracic muscles from a single blood meal matured to third-stage infective larvae within 192 hours. In contrast, development in S. metallicum was asynchronous, slower, and retarded. In this species many first-larvae were malformed and stunted after the 5th day of development; and microfilariae and first- and second-stage larvae were still present 8--10 days after a single infecting blood meal when third-stage larvae had developed. The development of O. volvulus in S. ochraceum is more compatible with the intense transmission associated with human disease.


Effect of diethylcarbamazine citrate on fourth stage and adult Brugia malayi in cats.

Sixty-three experimental and 58 control cats were infected with Brugia malayi so that the developing and adult worms localized in the regional lymphatics of the hind legs. At 20 days after infection when Brugia were in the 4th larval stage, and at 8 weeks when worms were young adults, cats were divided into groups to test the efficacy of diethylcarbamazine citrate (DEC) at various dosage levels. At 100 mg total DEC/kg no 4th-stage larvae were seen in 5 cats compared with a mean of 20.4 living larvae in each of 5 controls. At this level of DEC, 2 of 5 cats had 1 and 2 adult worms while 4 of 4 controls had a mean of 23.2 living adult worms. At 50 and 25 mg/kg there was a substantial reduction of both 4th stage and adult worms when compared to controls. At 10 mg/kg, 4 of 6 cats had 4th-stage larvae but at a lower level (mean = 7.0) than in 6 controls (mean = 23.2). No reduction of either 4th-stage larvae or adult worms was seen at 1 mg/kg. This study establishes the efficacy of DEC against 4th-stage and adult Brugia malayi in cats, although considerably higher levels of the drug were required than the level previously determined to kill 3rd-stage larvae. It appears that the cat-B. malayi model will be an effective method to compare the efficacy of drugs against adult lymphatic-dwelling filariae.


Schistosomiasis control in Puerto Rico: twenty-five years of operational experience.

A program to control schistosomiasis in Puerto Rico was initiated in 1953, using limited chemotherapy and snail control by environmental, biological and chemical means. At the same time, extensive programs of water supply, health education, and free latrine distribution were underway throughout the island. The impact of the program was evaluated initially by examinations of fecal samples from first-grade children until 1966, and subsequently by island-wide surveys using adult worm antigen for skin test on fifth-graders in 1963, 1969, and 1976. There was a decrease in the proportion of children reacting positively to the skin test from 24% in 1963 to 5% in 1976. The decrease in the proportion of positive skin test reactions was one and a half times as great in the area under snail control as in the rest of the endemic area, and most of the decrease outside the snail control program was due to improved water supply. Calibration tests indicated a decrease in prevalence among the entire population, if determined by multiple fecal exams, from 15% in 1963 to less than 4% in 1976. Thus the estimated number of persons passing eggs in Puerto Rico was about 100,000 in 1976, in a population of 3 million. The cost of snail control was minimized by emphasizing environmental and biological methods, showing that the disease can be controlled on a large scale with simple techniques. Eradication of the parasite from Puerto Rico is quite likely in the next few years with the advent of the new drug, oxamniquine, and would be a cheaper strategy than continued snail control.


Structure of the schistosome eggshell: amino acid analysis and incorporation of labelled amino acids.

Preparations of eggshells of Schistosoma mansoni and S. japonicum were hydrolyzed and analyzed for amino acid composition. Both species showed great similarities in the proportions of each residue found. The predominant amino acid in shell hydrolysates was found to be glycine, which accounted for 37% of S. mansoni and 45% of S. japonicum amino acids. Four components (glycine, aspartic acid, lysine, and serine) totalled 68--75% of amino acids in the eggshells. Other individual amino acids were present in relatively small proportions ranging from 5.2--0.01%. Less than 1% of the amino acid residues were identified as tyrosine, and bityrosine was detected at a level not exceeding 1 in 1,600 residues. Carbohydrates were estimated to comprise 7.5--10% of the eggshell weight, based on hexose assay, and glucosamine was identified as the principal amino sugar in shell hydrolysates. In vivo labelling of the S. mansoni eggshell was demonstrated following injection of C14-glycine and C14-tyrosine into infected mice and subsequent purification of the shells of eggs recovered from their liver.


Acedapsone in the prevention of leprosy: field trial in three high prevalence villages in Micronesia.

The 1,659 non-leprous people in a Micronesian population experiencing an annual leprosy incidence rate of about 7/1,000 were offered 15 acedapsone (DADDS) injections during 1967--1970 for leprosy prevention purposes. Subsequent annual surveillance showed an initial cessation of new cases during the 3-year DADDS campaign, followed by a resumption of cases thereafter at a yearly level of about 2/1,000 with a longer pause and slower rise among those who received the full regimen. A secondary wave of cases that has occurred since 1973 among children born after 1968 shows that post-campaign transmission occurred, probably principally from relapsing multibacillary cases with onset before the campaign. Recommendations are made for a balanced, long-term control program with DADDS preventive treatment limited to contacts of multibacillary cases.


Absence of leukocytes permissive to dengue 2 virus in the acute phase of dengue hemorrhagic fever.

Patients with primary dengue infection developed dengue 2 virus (D2V) permissive peripheral blood leukocytes (PBL) 2--3 weeks after infection. PBL from healthy individuals with dengue antibody were permissive to D2V in vitro, suggesting that immunologically mediated in vitro D2V permissiveness persists for a relatively long time after recovery from dengue infection. However, PBL obtained from second infection dengue hemorrhagic fever patients did not support D2V growth during the acute phase of illness but did so during convalescence. Leukocytes from dengue-immune patients with typhoid fever or non-dengue viral illness were permissive throughout both acute and convalescent phases of illness although there was tendency for increased permissiveness during convalescence. Acute phase PBL from DHF patients synthesized and secreted dengue neutralizing antibody in culture. Absence of D2V replication in these cultures was strongly, but not completely, correlated with antibody production. Other immunological mechanisms, in addition to antibody, may be operating in vitro or in vivo during acute phase dengue hemorrhagic fever to alter the permissiveness of PBL to D2V infection.


Isolation of St. Louis encephalitis virus in South Brazil.

Eight strains of a flavivirus identified as St. Louis encephalitis (SLE) virus were isolated from wild rodents, birds, and sentinel mice in three locations in the State of São Paulo, Brazil from 1967--1969. No illness attributable to SLE virus infection was detected among the local inhabitants, although about 5% of the local population had neutralizing antibodies to this virus.


Acquired resistance to ticks: expression of resistance by C4-deficient guinea pigs.

Hartley and C4-deficient guinea pigs developed resistance to the ixodid tick. Dermacentor andersoni, after one infestation. Resistance was characterized by resistant animals of both groups allowing significantly fewer larvae (5--25%) to engorge during a second infestation than during an initial infestation (70--90%). Resistant animals in both groups developed cutaneous reactions at the site of tick attachment which were characterized by intraepidermal vesicles containing numerous basophils. In previous studies, tick-resistant Hartley guinea pigs depleted of complement by cobra venom factor were not able to express the resistance response and the skin reactions at the tick attachment sites were depleted of basophils. The use of cobra venom factor as an anti-complement probe could not distinguish the relative importance of the classical and/or alternate pathways of complement activation in the expression of tick resistance. The present study reports that C4-deficient guinea pigs, those with a total deficiency in the classical pathway of complement activation, but with an intact alternate pathway, can acquire and display tick resistance in a fashion similar to Hartley guinea pigs. This finding provides evidence that the alternate pathway of complement activation is important in the expression of tick resistance.


Esophagoplasty with an autogenous tubed gastric flap.

As an esophageal substitute, a tubed gastric flap 2.5 cm in inner diameter and 38 cm in length, was constructed from the gastric wall along the greater curvature; a pedicle was attached to the gastric antrum, and its oral stump was brought up into the left supraclavicular fossa through a retrosternal tunnel to perform an esophagogastrostomy. Anastomotic breakdown occurred in only three of fifty cases in which this procedure was used.


Endoscopic retrograde cholangiopancreatography and gray-scale abdominal ultrasound in the diagnosis of jaundice.

Fifty-five patients with suspected obstructive jaundice were studied with both ERCP and abdominal ultrasound. Biliary tract obstruction was documented in 49 patients and parenchymal liver disease in 7. A definite cause of jaundice was demonstrated by ERCP in 45 of 49 patients with biliary tract obstruction but in only 28 of 49 patients by ultrasound. Bile duct dilatation, where present, was detected by ERCP in only 33 of 42 patients. ERCP was particularly effective in patients with common duct stones; common duct calculi and a dilated common duct were detected in 15 of 16 such patients. Dilated bile ducts where present were detected by ultrasound in 22 of 42 patients. Ultrasound was particularly helpful in patients with pancreatic cancer in whom a dilated common duct could not be opacified during ERCP. ERCP and abdominal ultrasound together provide a rapid and safe method of diagnosis in the jaundiced patient with suspected bile duct obstruction.


Hemorrhagic pancreatitis.

An experience with 68 patients with hemorrhagic pancreatitis identified at operation or autopsy is reported. Sixteen of the patients were subjected to operation, and 6 survived after celiotomy and peritoneal irrigation. There were no survivors in the unoperated group. Death when the pancreas is hemorrhagic and due to pancreatitis occurs an average of 10 days after the onset of symptoms or within 7 days of hospitalization. In eight patients who presented in coma, the diagnosis was not established before death. Early recognition of patients with hemorrhagic pancreatitis can be facilitated by the routine use of amylase and methemalbumin determinations and peritoneal lavage. Translocation of large volumes of albumin-rich fluid from the intravascular compartment to the retroperitoneum and pleural and abdominal cavities is in part responsible for many of the signs, symptoms, and complications of hemorrhagic pancreatitis. These include hemoconcentration, hypotension, tachycardia, tachypnea, ascites, abdominal distress, respiratory insufficiency, and renal failure. Adequate initial resuscitation and intensive follow-up are probably the most important elements in the management of patients with hemorrhagic pancreatitis. Careful monitoring of fluid and electrolytes and blood gases is required to avoid shock and renal and pulmonary failure. The need for careful monitoring is emphasized by the number of our patients in whom inadequacies of fluid replacement and ventilation were often not appreciated until the patient was in extremis from shock or respiratory or renal failure. Antibiotics are indicated in patients with biliary tract disease and penetrating ulcer in whom the risk of secondary infection is considerable. Associated diseases that initiated pancreatitis and that in themselves may be life-threatening, such as acute cholecystitis or cholangitis, should be promptly treated by operation. Diagnostic and therapeutic lavage are justified in the treatment of hemorrhagic pancreatitis. Resection of the necrotic pancreas should be considered when the patient fails to improve after lavage and nonoperative resuscitation.


Role of bilateral adrenalectomy (and oophorectomy) in the management of patients with metastatic breast cancer.

One hundred consecutive patients who underwent bilateral adrenalectomy for metastatic breast cancer with at least a 2 year "tumor-free" interval and with symptomatic bony, local-regional, pleural, or discrete pulmonary or mediastinal metastases had objective remission rates of 65 per cent at 6 months, 48 per cent at 12 months, 28 per cent at 18 months, and 16 per cent at 24 months.


Evaluation of peritoneal closure at laparotomy.

Laparotomy closure was performed in rats with and without peritoneal suture. Both paramedian and midline incisions were used. The incidence of adhesions to the parietal peritoneum was significantly higher when the peritoneum was sutured, more so with catgut. The peritoneal surface reperitonealized in 7 days when peritoneum was not sutured. The tensile and bursting strength was studied on the 7th and 14th day, and was found to be similar in both midline and paramedian incisions whether or not the peritoneum had been sutured. The same results were obtained whether continuous or interrupted sutures of the muscle sheath with monofilament nylon was used. We believe that the peritoneum should not be sutured at laparotomy closure and that a midline incision with rectus sheath closure using monofilament nylon should be used as it is less time-consuming and provides sufficient strength to the abdomen.


Long-term results of femoroinfrapopliteal bypass in diabetic patients with severe ischemia of the lower extremity.

In patients with severe lower extremity ischemia (ischemic necrosis or pain at rest associated with physical findings of peripheral arterial insufficiency), diabetes mellitus should not deter thorough arteriography and consideration of arterial reconstruction. Infrapopliteal bypass can produce prolonged limb salvage in diabetic patients in lieu of primary amputation.


Pancreatic cystadenoma of the spleen.

A cystadenoma of the pancreas within the spleen from pancreatic heterotopia is described. The tumor was located in the hilum of the spleen and completely separated from the normal pancreatic tail. This fact strongly supports the possibility that this tumor arose from pancreatic heterotopia.


Duodenal and jejunal atresia with agenesis of the dorsal mesentery: "apple peel" small bowel.

Two newborn infants with duodenal and jejunal atresia and agenesis of the dorsal mesentery represent our surgical experience with "apple peel" small bowel or "christmas tree" demormity. The first patient had the typical appearance of this condition. The postoperative course was complicated by hyperbilirubinemia, septicemia, and disseminated intravascular coagulation. The infant is in satisfactory condition 1.5 years after operation. The second patient had agenesis of the dorsal mesentery without spiraling of the bowel around its vascular stalk. The child died after 1 month, with complete absence of extrahepatic bile ducts as seen at a second laparotomy. Neither child had been subjected to gastrostomy.


Pneumatosis cystoides intestinalis. Report of two cases involving the descending colon.

Two cases of pneumatosis cystoides intestinalis of the descending colon are described in which the presenting symptoms were abdominal pain and changed bowel habits, respectively. The diagnosis in both cases was established radiologically and sigmoidoscopically. Because the symptoms were persistent and severe, surgical excision of the involved segment of the large bowel was performed. The postoperative result was good and both patients remain free of symptoms.


A safe method for pyloromyotomy.

Pyloromyotomy often ends up as a pyloroplasty because of accidental lesions on the duodenal mucosa. This can be avoided. If the incision in the serosa is Y-shaped, the fold of mucosa that partly covers the pyloric muscle can be pushed distally and escape being punctured.


Technic of resection of mesenteric tumors.

In the resection of mesenteric tumors or primary malignant lesions of the small bowel, exposure of the superior mesenteric vessels is important. This is the necessary criterion of resectability and the condition of obtaining maximal margins in the lymphatic drainage area. It also helps avoid unnecessary sacrifice of branches and tributaries to the superior mesenteric vessels from uninvolved portions of the bowel.


Upper limb ischemia resulting from arterial thromboembolism.

Acute ischemia of the upper limb is commonly caused by trauma and embolic arterial occlusion. However, primary atherosclerotic thrombosis is found infrequently and concern regarding its incidence, recognition, and treatment prompted a review of our clinical experience. Of 36 patients with acute ischemia of the upper limb, 17 (47.2 per cent) had embolic occlusion, 9 (25 per cent) iatrogenic thrombosis in the brachial artery, and 10 (27.8 per cent) primary arterial thrombosis. Of the total group, noncardiac arterial emboli (two patients) and primary atherosclerotic thrombosis (six patients) accounted for 8 of 36 (22.2 per cent) ischemic limbs. Including 2 additional patients who had atherosclerotic thrombosis associated with trauma, the total number represented 10 of 36 (27.8 per cent). An aggressive approach to the undiagnosed patient with acute ischemia of the upper limb is warranted, including the use of arteriography in most cases. In patients with iatrogenic thrombosis in the brachial artery, we believe that the routine use of intraoperative arteriograms may improve the operative results.


Factors influencing the complications of colostomy closure.

This retrospective review of 206 colostomy closures performed by different methods and at various intervals from the time of creation of the stoma suggests that attention to meticulous surgical technic is the most important factor in limiting the morbidity and mortality of this commonly performed procedure. Considerations of the location and type of colostomy, timing, method of closure, and patient population seem to be less importnat than suggested in previous reports.


Relation between immunity and survival in carcinoma of the colon and rectum.

Twenty-two patients with cancer of the colon and rectum were evaluated before and after surgical treatment by leukocyte migration inhibition assays using autologous and allogeneic tumor extracts. All patients were resected for cure. Patients with cancer of the colon demonstrated significant migration inhibition against autologous extracts before surgery and in the immediate postoperative period. Patients with rectal cancer did not demonstrate significant migration inhibition at any time. The possibility that immunity plays a role in the poorer prognosis of patients with rectal cancer is discussed.


Intraarterial infusion chemotherapy (5-fluorouracil) in patients with inextirpable or locally recurrent rectal cancer.

A retrospective analysis of the results of treatment of advanced rectal cancer of the pelvis with regional intraarterial infusion of 5-fluorouracil (5-FU) is reported. A special technic for positioning the catheters selectively in the internal iliac arteries justifies this analysis. Four patients with primary inextirpable rectal cancer and 10 patients with locally recurrent rectal cancer have been treated. No immediate mortality was noted. Relief of pain was noted in two-thirds of the patients. An objective tumor response was noted in three patients with locally recurrent disease. In one patient with primary inoperable cancer it was possible to extirpate the tumor after infusion therapy. An improvement in quality of life during the first 2 months after therapy was achieved in half of the patients as judged by their performance. Complications were not serious. Hematomas with infection were seen in one patient, two patients had septicemia, and three patients had transient oliguria. Transient thrombocytopenia was reported in two patients. The results indicate that infusion therapy produces a reasonable response such as palliation of pain. Only minor complications were seen and easily controlled. The advantages of infusion therapy are that it can be given in a reasonable time with only a short hospital stay.


Surgical significance of the histopathology of the common bile duct.

Silver biopsies of the common bile duct were obtained from 15 patients with clinical and surgical evidence of cholangitis. The most pronounced histologic changes were edema, congestion, and marked mucous gland hypertrophy and hyperplasia. No ulceration, intramural abscess, or areas of necrosis were found. Clinical cholangitis is not associated with necrotizing changes in the duct wall. This fact is the histologic basis for satisfactory healing of choledochal enteric anastomoses performed in the presence of cholangitis.


Resectability and functional reserve of the liver with obstructive jaundice in dogs.

Fifty-five dogs were used to evaluate the resectability of the liver with obstructive jaundice. Cholecystectomy and ligation of the distal common bile duct were used to produce obstructive jaundice. It was found that 40 per cent of the liver with obstructive jaundice was resectable with biliary decompression 2 weeks after ligation. At 1 week after induction of obstructive jaundice, 70 per cent hepatectomy with biliary decompression may be tolerated with careful postoperative management. From serum chemical studies it was found that if the serum albumin level was below 2.0 g/dl, 60 per cent of the dogs died after 40 per cent hepatectomy and all died after 70 per cent hepatectomy. From the standpoint of hepatic functional reserve 40 per cent hepatectomy is successful if the maximal removal rate of indocyanine green is above 0.14 mg/kg/min. Hepatic functional reserve is reliable for predicting the risk of hepatectomy, and it correlates well with the rate of hepatic regeneration after hepatectomy.


Analysis of benign breast lesions in blacks.

A clinicopathologic analysis of 202 benign breast lesions in black women is presented. The study shows that the peak incidence of fibroadenoma occurs at an earlier age in black than in white patients. Fibrocystic disease is most frequent in both black and white patients between 25 and 45 years of age. It is noteworthy that nulliparous adolescent blacks have a higher risk of fibroadenoma developing and our findings confirm the observation made by Funderburk et al [5] and Nigro and Organ [6] that the incidence of fibroadenoma in blacks is high. The low incidence of fibrocystic disease in our patients does not reflect the clinical incidence of the disease because most patients with fibrocystic disease do not undergo biopsy. We are unable to draw any conclusions about the relation between the use of oral contraceptives and the incidence of benign breast disease. In conclusion, a review of the literature and an analysis of our data suggest a relatively higher incidence of fibroadenoma among black patients. In contrast to the finding in the white population, it appears that in blacks fibroadenoma is more common than carcinoma of the breast.


Hypercalcemia and malignant melanoma.

Malignant melanoma occurs in approximately 1.7 per cent of all patients admitted to the Clinical Center, National Institutes of Health, and approximately 1.8 per cent of patients admitted with hypercalcemia and malignant disease. The incidence of hypercalcemia and malignant melanoma is 1.1 per cent. Bone metastases are diagnosed before death in approximately 5.2 per cent of patients with malignant melanoma. The cause of hypercalcemia in our patients appears to be bone metastases in 83.3 per cent and primary hyperparathyroidism in 16.9 per cent.


Treatment of postradiation stricuture of the rectum by the modified Duhamel procedure.

Benign rectosigmoid stenosis secondary to pelvic radiation presents a difficult problem in management and is usually treated by permanent colostomy with its attendant discomfort and inconvenience. Other approaches include low anterior resection or even transsacral resection of the affected area of rectosigmoid, but they involve risk to rectal, bladder, and sexual function. The Martin modification of the Duhamel procedure is specifically designed to avoid these problems and was used successfully in the present case for treatment of rectosigmoid stenosis. The patient has been followed up 8 years and reports normal sensation and function of bladder and rectum and no disturbance of sexual function.


Acute torsion of the gallbladder.

Torsion of the gallbladder is an uncommon process that is usually found at the time of exploration for an acute surgical abdomen. It results from two congenital anomalies and may be complete or partial. It should be considered in the etiology of what appears to be acute cholecystitis in the elderly, thereby prompting early surgical management. Two cases are presented to help define the true incidence of this process.


Management of aortocaval fistula due to abdominal aortic aneurysm.

Anasarca and intractable congestive heart failure were the presenting signs of an abdominal aortic aneurysm with aortocaval fistula. Management with careful monitoring of cardiovascular function using a Swan-Ganz catheter before, during, and after surgery resulted in an uneventful recovery.


Corrosive injury to the stomach: the natural history and role of fiberoptic endoscopy.

Most physicians recognize that the ingestion of lye is associated with severe esophageal damage. It is much less widely known that gastric injury is the predominant finding when acid is ingested. We are reporting on five patients who had severe gastric damage after ingestion of diluted sulfuric acid (three cases), capsules of potassium hydroxide, and Clinitest tablets (one case each). Fiberoptic endoscopy was used to localize the extent and severity of injury and to follow the evolution of the damage. The extent and location of injury varied with the amount and type of agent ingested. Acid ingestion resulted in severe gastritis, which eventually led to antral stenosis and gastric outlet obstruction requiring operative intervention in two cases. Potassium hydroxide capsules produced diffuse esophagitis, gastritis, and a non-healing large gastric ulcer. Clinitest tablets produced distal esophagitis and stricture and antral damage leading to gastric outlet obstruction which required operative intervention. These cases demonstrate the natural history of corrosive injury to the stomach and the value of fiberoptic endoscopy in the management of this problem.


Mesenteric revascularization: an operative approach.

Chronic intestinal ischemia was successfully treated with isolated superior mesenteric revascularization despite the involvement of multiple visceral arteries. An operative approach was used in which both the aorta and the superior mesenteric artery were exposed in the area between the inferior border of the pancreas and the superior border of the fourth portion of the duodenum. This approach is applicable in thin patients and allows a short, horizontal graft that appears to increase long-term patency.


Improved cannula for operative (cystic duct) cholangiography.

A new S-shaped cystic duct metal cannula was developed and used successfully in 200 cystic duct cholangiograms. It has the advantage of being easy to manipulate because the configuration does not obscure the vision and the resistance is less than that of plastic tubes, facilitating injection with lower pressure. It is much cheaper than the disposable cannulas because it can be reused (autoclaved).


A study of HLA antigen distribution in families with atopic dermatitis.

Seventeen children presenting with atopic dermatitis were HLA typed together with their parents and siblings. A total of 89 individuals was studied. No close link between HLA antigen distribution and clinical expression of atopy was demonstrated, and 14 HLA identical but disease-free siblings were identified. An increase in the A1 B8 haplotype was observed in the families as a whole by comparison with a large control series.


Antibody-dependent monocyte-mediated cytotoxicity in severe atopic dermatitis.

Antibody-dependent monocyte-mediated cytotoxicity was studied in nine patients with severe atopic dermatitis during flares of their disease. In all cases the cytotoxicity was depressed. The disturbed function may contribute to the severe cutaneous infections seen in these patients. It remains to be seen if these patients have an intrinsic monocyte defect or if an inhibiting factor only is operating during active disease states.


Occupational allergy in nurses to a bulk laxative.

Finely ground psyllium (Plantago ovata) seeds, so-called ispaghula powder is used in bulk laxatives. During the dispensing of these medicines some dust is generated. Allergic symptoms from exposure to this dust was reported by two nurses, one of whom was wroking in a department where exposure to the powder could be considered high. Nineteen other subjects working in the same department were investigated with regard to allergy to ispaghula powder. An extract from ispaghula powder was made and used in RAST and skin tests. Exposure tests with ispaghula powder mixed with crushed rusks were made in symptomatic subjects. Eight out of the 20 investigated subjects from this department reported symptoms which could possibly have been elicited by ispaghula powder. Evidence of sensitization was found in five of them. The use of less dusty (granulated) forms of ispaghula laxatives might diminish the risk of sensitization.


Methohexitone and etomidate for bronchoscopy.

General anaesthesia for bronchoscopy has been provided with either methohexitone or etomidate, with and without fentanyl. Recovery was faster following methohexitone and there was no statistically significant difference in the incidence of complications. Inclusion of fentanyl in the technique did not confer any benefits with either drug.


The ocular effects of etomidate.

Etomidate, a new intravenous hypnotic agent, significantly lowered the mean intraocular pressure (IOP) of fifty patients within 30 s of an intravenous injection from 15.7 to 9.5 mmHg. This effect was present even during the administration (to twenty patients) of low doses (0.25 mg/kg) when the mean reduction was from 15.6 to 7.6 mmHg. The reduction in IOP was unaffected by the presence of muscle movement. Low frequency pendular nystagmus was observed in five patients.


A complication of subarachnoid phenol blockade.

The authors have described a fatal complication which occurred after a cervical subarachnoid block with phenol in glycerine. As a result of this experience they advocate the use of a dose of phenol of not more than 2 ml, which is smaller than that sometimes recommended, and also emphasise most strongly the importance of careful positioning of the patient.


O2 and N2O analysis with a single intravascular catheter electrode. An in-vitro study.

The simultaneous measurement of O2 and N2O in liquid, using a single polarographic catheter electrode, is described. It is shown that commercial PO2 intravascular electrodes, with silver cathodes, produce separate and distinct polarograms for O2 and N2O, and that these electrodes can be used for the measurement of both PO2 and PN2O.


Cardiac pacemaker insertion: a study of the anaesthetic and postoperative complications.

One hundred and three patients undergoing pacing procedures have been studied, the majority requiring the insertion of an epicardial system under general anaesthesia. The main findings were of an elderly group of patients with a high incidence of associated disease, who suffered predominantly from pulmonary and renal complications. Methods of reducing these complications, particularly in relation to general anaesthesia are discussed.


The use of procaine hydrochloride as a continuous lumbar epidural technique in labour.

A continuous technique for lumbar epidural during labour is described, using procaine hydrochloride without adrenaline. An investigation was undertaken to determine the action of procaine in labour, to determine whether this drug could facilitate a normal delivery and to study maternal and fetal blood procaine levels. The technique, although successful, offered no specific advantages.


Plasma potassium, sodium and blood sugar following etomidate and suxamethonium.

Changes in plasma potassium, sodium and blood sugar were studied in Nigerian patients following induction of anaesthesia with etomidate and suxamethonium. Healthy patients presenting for elective surgery as well as psychiatric patients presenting for electroconvulsive therapy were studied. Plasma potasium was essentially unaffected by etomidate administration, but rose significantly when suxamethonium was given. This rise was higher than that observed with thiopentone and suxamethonium in a previous study on a similar group of Nigerians. Blood sugar was not significantly increased by the administration of etomidate but rose significantly after suxamethonium was given. This hyperglycaemic response was greater than when thiopentone was used as the induction agent. Administration of ECT was associated with a further increase in blood sugar. It is concluded that thiopentone is preferable to etomidate in situations where increases in plasma potassium and blood sugar are undesirable following administration of suxamethonium.


Continuous epidural infusion of bupivacaine in labour: a simple method.

Thirty patients were given a constant epidural infusion in labour by gravity feed drip of approximately 10 ml of 0.25% bupivacaine per hr. The infusion proved a simple and reliable method of ensuring adequate analgesia throughout labour. There were no problems of drug toxicity and the incidence of complications and side effects was comparable to a previous series using intermittent 0.5% bupivacaine.


The reduction of amnesic wakefulness during caesarean section.

Wakefulness during general anaesthesia was assessed by the isolated forearm technique in two groups of patients for Caesarean section. The anaesthetic was based on the use of oxygen 66%, nitrous oxide 33% and halothane 0.4% during the induction delivery interval. There was a highly significant reduction in wakefulness in the Group who received nitrous oxide at 66% for the first 3 min only. The wakefulness was amnesic in all cases.


Thiopentone anaphylaxis.

A fit young mother had a severe anaphylactic response to intravenous injection of sodium thiopentone, having been sensitised nearly 20 years previously.


Skin depigmentation associated with intravenous anaesthetic induction agents.

A case of skin depigmentation associated with intravenous anaesthetic induction agents is described. The differential diagnosis is briefly discussed.


Anaphylactoid response to intravenous tubocurarine.

A case of severe anaphylactoid reaction to tubocurarine in a 42-year-old female is described. This is particularly notable as there was no history of past allergies or of previous exposure to the drug.


Fatal reaction to haemaccel.

A case is described of fatal bronchospasm which was probably due to an allergic response initiated by 'Haemaccel'.


Three knifings in Gloucester.

Three cases of knife stabbing are described. The diagnosis of pneumothorax and its management are discussed. Conservative treatment of stab wounds of the chest can be applied in most cases. Abdominal wounds need to be explored.


High capacity suction technique. A method of reducing the aspiration hazard during induction.

A suction booster is described which may be interposed between the endotracheal tube and the main suction system. This allows suction to be instantly ready throughout the intubation procedure, the rate of suction to be increased up to ten-fold, and all solid particles which can pass through the tracheal tube to be removed without the risk of blockage.


Synaptic extensions from the mossy fibers of the fascia dentata.

In the hilar region of the rat hippocampus, filamentous extensions have been observed to originate from the en passant synaptic expansions on the so-called mossy fibers, which are the axons of the dentate granule cells. These extensions range in length from about 1 micrometer to 30 micrometer, are often branched, and appear to contact the processes of various cell types in the hilar region. In 28-day-old rats, there are between 4 and 9 such extensions from most mossy fiber expansions, and the total length of the extensions from any one expansion is on the order of 75 micrometer. Analysis of serial electron micrographs through normal and Golgi-impregnated mossy fibers has confirmed that these extensions are, indeed, presynaptic processes. Each contains one or more vesicle-rich foci along its length, and is associated with asymmetric membrane specializations. At these sites, the extensions are in synaptic contact with dendrites and dendritic spines of, as yet, unknown origin. A quantitative analysis of these extensions in Golgi material from rats at different ages indicates that they reach their greatest length around 14 days and then decline to adult values by 28 days.


The development of cholinergic ganglia in the chick embryo heart.

Cholinesterase activity was investigated in the heart of the developing chick from the 6th to 20th day of incubation. The earliest cholinesterase-positive nerve cells and fibers could be demonstrated between the 7th and 9th day. On the 13th day the nervous structure attained full development comparable with that seen in the hatched chicken. The number of ganglia increases up to the 15th day, and remains constant thereafter. The right ventricle is associated with the largest number of ganglia.


Electron microscopic investigations on the differentiation of Purkinje cells in the ontogenetic development of the chicken heart.

The ultrastructural development of subendocardial Purkinje cells of chicken left ventricle was investigated. In 9-day-old chick embryos the cell diameter and the organization of the cell organelles allow a distinction between Purkinje cells and ordinary myocardial cells In 14-day-old chick embryos, Purkinje cells show large accumulations of myosin filaments with interspersed ribosomes in addition to normomeric myofibrils. In these accumulations actin filaments seem to be absent. The deficiency of actin filaments is supposedly the reason for the random distribution of the myosin filaments. Purkinje cells of early chick embryos show areas with densely packed glycogen granules. In older embryos the glycogen concentration declines and only separate glycogen granules are visible. At hatching time the first subsarcolemmal leptomeric fibrils were observed in Purkinje cells. Leptomeric complexes arising in a close spatial relationship to the accumulations of myosin filaments and ribosomes can be seen in 2--4 week-old chickens. With the increasing age of the chickens, the size of these accumulations declines. Adult hens exhibit smaller accumulations, mainly in the neighborhood of leptomeric complexes. Purkinje cells show a distinct ontogenetic development. They are not simple embryonic remnants of ordinary myocardial cells.


The limbus spiralis and its relationship to the developing tectorial membrane in the cochlear duct of the Guinea pig fetus.

The development of the interdental cells of the limbus spiralis and of the inner spiral sulcus cells as well as the formation of the mesenchymal teeth of Huschke are described during fetal life up to the day of birth in the guinea pig. Additionally, the changes of the developing tectorial membrane are studied. The ultrastructural observations allow the conclusion that during fetal development at least a considerable part of the material of the tectorial membrane is secreted by the interdental cells of the limbus spiralis.


SEM study of the choroid plexus of the lateral ventricle in the cat.

Corrosion casts of the complete vascular network of the choroid plexus of the lateral ventricle in the cat brain were studied in SEM using the injection-replication method. The villi of this plexus are located only on its supero-anterior and infero-posterior parts, being most densely packed in the former region, close to the interventricular foramen. The capillaries of the villi display small nodular thickenings, which suggest the presence of small, sinusoidal dilatations. The main vessel supplying the plexus with blood is the anterior choroidal artery. The plexus is also characterized by a particularly rich venous network, which is drained by a prominent (main) choroid vein. The vascular organization of the choroid plexus of the lateral ventricle in cat is compared to that of the corresponding plexuses in other mammals.


Lipofuscin in the cerebellar cortex of albino rats: an electron microscopic study.

The ultrastructure of autofluorescent, PAS-positive lipofuscin in Purkinje, granule, Golgi epithelial, basket and stellate, microglial and perivascular cells in the cerebellar cortex of senescent rats is described. The membrane-bounded pigment is composed of three elements: 1) electron-lucent homogeneous droplets, 2) a granular matrix and 3) intensely osmiophilic patches. The proportions of these three components vary between cell types and one can grossly differentiate a neuronal and a glial lipofuscin. The lipofuscin granules of stellate and perivascular cells are different from lipofuscin of other cerebellar neurons and glia. It can be concluded from these morphological observations that each cerebellar cell type has its distinct lipofuscin.


Blood vessels in the tongue of the kitten: scanning electron microscopy of microcorrosion casts.

The subepithelial blood vessels of the dorsal surface of the tongue in young kittens has been studied by scanning electron microscopy of micro-corrosion casts. These vessels entwine the vallate papillae distributed in the pharyngeal part of the tongue, form hairpin loops in association with the small conical papillae along the sides and at the tip of the tongue and establish regularly distributed subpapillary conglomerations over almost its entire oral part. These conglomerations lie directly on veins. Small arterioles reach the vessels surrounding the individual subpapillary conglomerations. By contrast with the arrangement of the superficial vascular bed in the tongue of the dog and some other mammals, no anastomoses between arteries and veins were observed in the kitten between the vessels which supply and drain the subepidermal capillaries.


Stages in the prenatal development of the Chinese hamster (Cricetulus griseus).

A system of staging embryos is described for the Chinese hamster (Cricetulus griseus). This system of staging, based on Streeter's developmental horizons in human embryos, comprises three sets of criteria: 1) data on postconceptional age, size and number of somites, 2) external characteristics and 3) internal characteristics. A comparison has been made with data in mouse (Theiler, 1972) as well as in primates. It seems that the order of organogenesis, i.e. the sequence in which individual organs are formed, is basically similar in all mammals stuied so far.


Barbiturate protection in tolerant and nontolerant hypoxic mice: comparison with hypothermic protection.

The effects of pentobarbital on survival times of mice exposed to oxygen, 5 per cent, were studied over a large dosage range in normal mice and in mice made tolerant to the effect of barbiturates. Tolerance was induced by pretreatment with phenobarbital, 210 mg/kg, for three days, which increased the median anesthetic dose (AD50) for pentobarbital from 34 to 53 mg/kg. In nontolerant mice there was a dose-related increase in mean survival times for doses between 35 and 60 mg/kg, with a maximum increase to 303 per cent above control. At doses of more than 60 mg/kg survival times progressively decreased toward control. For tolerant mice survival time as a function of pentobarbital dosage was shifted to the right, i.e., protection necessitated higher doses. This shift was not explained by lower brain concentrations of pentobarbital in tolerant animals, but rather parallelled the increased tolerance to the anesthetic effect of the barbiturate. The authors conclude that in this model the protective effect of barbiturate is a function of the anesthetic effect rather than the barbiturate concentration in brain per se. Hypothermia (29 C) resulted in an increase in mean survival time comparable to that in barbiturate-treated animals. This supports the hypothesis that protection is ultimately a function of decreased cerebral metabolism, whether produced by anesthesia or by hypothermia. This model measures only the effect on spontaneous respiration during hypoxia. It is possible that other mechanisms are involved if barbiturates protect in other situations, such as during or after periods of complete ischemia.


Left ventricular function and compliance in swine during halothane anesthesia.

Halothane (0.05--1.7 vol per cent end-tidal) in nitrous oxide (N2O), 60 per cent: oxygen (O2), 40 per cent was administered to nonmedicated, closed-chest pigs. Ventricular function was analyzed from cardiac output (thermodilution) and left ventricular (LV) pressure indices. Ventricular volumes and compliance were estimated from single and biplane LV angiography. In separate experiments, the effects of N2O, time, and the angiographic dye injections were shown to be minimal. Halothane caused dose-dependent decreases in aortic blood pressure, cardiac output, peak first derivative of left ventricular pressure (LV dP/dt), the in-vivo maximum velocity of fiber shortening (Vmax), and ejection fraction; non-dose-dependent decreases in heart rate and circumferential fiber shortening rate. Although a pronounced dose-related negative inotropic effect of halothane in the pig heart was demonstrated, there was no definite effect on ventricular pressure-volume relationships (compliance). If there was any such effect of halothane, it was obscured by the cardiac depression produced.


4-Aminopyridine potentiates neostigmine and pyridostigmine in man.

To elucidate the interaction of 4-aminopyridine with neostigmine and pyridostigmine, the authors studied 57 anesthetized surgical patients using a technique of constant infusion of pancuronium to quantitate antagonist activity. 4-Aminopyridine, 0.15 or 0.35 mg/kg, produced no antagonism, while 0.5 mg/kg produced a mean 24 +/- 6 per cent (peak) antagonism. The dose that produced 50 per cent antagonism (ED50) of neostigmine alone was 22 micrograms/kg; with 0.35 mg/kg 4-aminopyridine, it was 7 micrograms/kg. The ED50 of pyridostigmine alone was 110 micrograms/kg; with 0.35 mg/kg 4-aminopyridine, it was 27 micrograms/kg. 4-Aminopyridine prolonged the onset times of both neostigmine and pyridostigmine, but prolonged the duration of action of neostigmine only. At a given level of antagonism of pancuronium, adding 4-aminopyridine 0.35 mg/kg, to neostigmine and to pyridostigmine decreased the amounts of atropine needed to prevent a change in heart rate by 68 and 70 per cent, respectively. The authors conclude that 4-aminopyridine potentiates antagonism of a pancuronium-induced neuromuscular blockade by neostigmine or pyridostigmine. Also, less atropine is needed to prevent cardiac muscarinic stimulation when 4-aminopyridine is used with either neostigmine or pyridostigmine.


Sister chromatid exchanges induced by inhaled anesthetics.

There is sufficient evidence that anesthetics may cause cancer to justify a test of their carcinogenic potential. Baden, et al., using the Ames test, a rapid and inexpensive genetic indicator of carcinogenicity, have shown that among currently used anesthetics fluroxene alone caused bacterial mutations. The authors used the sister chromatid exchange (SCE) technique, another rapid assay of mutagenic-carcinogenic potential. The frequency of sister chromatid exchanges in Chinese hamster ovary cells increases when the cell cultures are exposed to mutagen-carcinogens, particularly in the presence of a metabolic activating system. With this test system a one-hour exposure to 1 MAC nitrous oxide, diethyl ether, trichloroethylene, halothane, enflurane, isoflurane, methoxyflurane, or chloroform did not increase SCE values. Divinyl ether, fluroxene and ethyl vinyl ether increased SCE values in the same circumstances. Results of this study of mammalian cells suggest that no currently used anesthetic is a mutagen-carcinogen. The results also suggest that anesthetics containing a vinyl moiety may be mutagen-carcinogens.


Pharmacokinetics of lidocaine in fetal and neonatal lambs and adult sheep.

The pharmacokinetics of lidocaine were studied in fetal and neonatal lambs and in pregnant and nonpregnant adult sheep. Catheters were implanted in the femoral vessels and in the urinary bladders of animals prepared for chronic study. Lidocaine, 5--10 mg/kg, was injected intravenously either into the fetus or newborn lamb or into nonpregnant adult sheep. Serial samples of arterial blood and urine were obtained over four hours and analyzed for unchanged lidocaine using a gas chromatographic technique. The elimination half-lives of lidocaine in the bloods of nonpregnant ewe, neonate and fetus were 31, 51 and 33 min, respectively. Total-body clearances in the neonate and adult were 53 and 41 ml/min/kg. The metabolic clearances of lidocaine were the same in both, and approximated hepatic blood flow. Renal clearance was greater in the neonate, which was attributed to differences in urinary pH values and extents of protein binding. Thus, despite differences in half-lives, the newborn lamb is as capable as the adult of clearing lidocaine.


Rapidly developing tolerance to acute exposures to anesthetic agents.

Following the observation that mice manifest a characteristic withdrawal syndrome after an hour of exposure to nitrous oxide, the authors reasoned that there might be a very rapidly developing tolerance to nitrous oxide. Thus, they determined the inspired concentrations that cause loss of the righting reflex in mice (i.e, the ED50), in the presence of 1 atm of oxygen, of: 1) nitrous oxide alone; 2) cyclopropane alone; 3) nitrous oxide plus 13.6 atm helium; 4) ethylene plus 13.6 atm helium. In each instance the ED50 was determined after averages of 6,34 and 64 min of exposure to the anesthetic agents. For nitrous oxide alone the ED50 at 6 min was 1.18 +/- 0.049 atm, increasing to 1.39 +/- 0.061 atm at 64 min. For ethylene plus helium the ED50 increased from 1.21 +/- 0.033 atm at 6 min to 1.31 +/- 0.039 atm at 64 min, indicating the development of acute tolerance. Neither cyclopropane alone nor nitrous oxide plus helium caused acute tolerance. This absence of tolerance may have resulted from a slower development of an alveolar anesthetic concentration.


Uterine blood flow and plasma norepinephrine changes during maternal stress in the pregnant ewe.

Because maternal stress may adversely affect the fetus, the authors tested the effects of brief episodes (15-60 sec) of maternal stress in 18 awake pregnant ewes. Maternal agitation and stuggling occurred either following non-painful stimuli such as loud noises or sudden movements of personnel (ten animals) or following the brief application of the ewe's skin of a uniform electrical stimulus of 30 volts with a frequency of 167 Hz for 30-60 sec (eight animals). Stimulation of either type produced a 45-50 per cent increase in mean maternal arterial blood pressure and a concomitant 32-52 per cent decrease in uterine blood flow (P less than 0.05). The decreases in uterine blood flow were brief, lasting less than 3 min, and were not associated with fetal asphyxia. Maternal plasma norepinephrine levels were measured following electrically induced maternal stress and were increased 25 per cent. The authors conclude that maternal stress may decrease uterine blood flow secondary to release of endogenous norepinephrine.


Densities of liquid anesthetics at 37 C.

Liquid densities of chloroform, diethyl ether, enflurane, halothane, methoxyflurane, and trichloroethylene were measured at 37.0 C. The maximum error in the density values was estimated to be +/-0.01 per cent.


Steriod therapy for pneumonitis induced in rabbits by aspiration of foodstuff.

The instillation of gastric contents, 0.5 ml/kg (pH 4.3), containing small food particles into the left diaphragmatic lobe of the lungs of 49 rabbits caused severe aspiration pneumonitis. Administration of methylprednisolone, 30 mg/kg, intramuscularly, every eight hours for three days to 26 of the 49 rabbits did not alter the rate of roentgenographic resolution of the pneumonitis. Corticosteroids did decrease the fibroblastic response of the lung to the aspirate, but also interfered with healing of granulomatous lesions.


Inhibition by ether of glucose-stimulated insulin secretion in isolated pieces of rat pancreas.

Addition of glucose (16.7 mM) to isolated pieces of rat pancreas increased insulin secretion 5.4-fold over basal secretion rates. Ether at 1, 1.5 and 2 MAC inhibited this insulinogenic effect of glucose in a dose-related manner by 5, 18 (P less than 0.01) and 29 (P less than 0.01) per cent, respectively.


Halothane biotransformation in anesthetists.

Serum bromide levels were measured in 115 anesthetists by use of x-ray fluorescence spectrometry. Bromide levels peaked at 184 +/- 21 micron in anesthetists regularly exposed to halothane (n = 20), at 58 +/- 4 micron in anesthetists sporadically exposed to halothane (n = 71), and at 46 +/- 3 micron in nonexposed anesthetists (n = 24). Kinetic studies were carried out in five other anesthetists after ten days of exposure to halothane. Average daily halothane concentration was 19.2 +/- 3.2 ppm; duration of exposure was 3.8 +/- 0.2 hours/day. Mean serum bromide level increased from 40 +/- 4 micron before exposure to 220 +/- 36 micron on the last day of exposure. Serum bromide half-life was 14 +/- 1.7 days. The study demonstrates that anesthetists debrominate halothane in a dose-related fashion. Serum bromide levels achieved, however, were far below those reported to result in clinical bromism.


Perfusion of naloxone through the fourth cerebral ventricle reverses the circulatory and hypnotic effects of halothane in dogs.

To determine whether naloxone when perfused through the cerebroventricular system would modify the circulatory and hypnotic effects of halothane, the authors studied its effect in six trained dogs. Naloxone, 20 microgram/ml, was perfused through the fourth cerebral ventricle in three and through the third cerebral and lateral ventricles in three other dogs when awake and during halothane anesthesia (0.75--0.82 vol per cent in oxygen). Blood pressure, heart rate, and circulatory responses to bilateral occlusion of the carotid arteries were measured. The state of consciousness was evaluated by the animals behavior and the EEG. Arterial hypotension, bradycardia, depressed baroreceptor responses, and EEG synchronization associated with halothane anesthesia were reversed when naloxone was perfused through the fourth ventricle. To maintain comparable depths of anesthesia the halothane concentration had to be doubled during naloxone perfusion. No change in the circulatory or hypnotic effects of halothane occurred when the third ventricle was perfused with naloxone. It is concluded that opiate receptors in structures bordering the fourth cerebral ventricle may be important modulators of inhalational anesthesia.


The effects of deuteration on the metabolism of halogenated anesthetics in the rat.

The authors studied the effects of substituting deuterium for hydrogen in several volatile anesthetics on their metabolism in the Fischer rat. Substitution of deuterium in the ethyl portion of methoxyflurane increased the metabolic production of fluoride ion by 19 per cent when administered at a concentration of 0.05 per cent. Total replacement of hydrogen by deuterium resulted in a 29 per cent decrease in the amount of fluoride produced, while deuteration of only the methoxyl group produced a 33 per cent decrease in fluoride produced. Deuteration of halothane resulted in a 15 or 26 per cent decrease in serum bromide at 0.75 per cent or 1.0 per cent, respectively. Deuteration in the ethyl portions of enflurane and two experimental agents, CF2HOCF2CFBrH and CF2HOCF2CCl2H resulted in 65, 76, and 29 per cent decreases in urinary fluoride, respectively. Anesthesia with deuterated chloroform at a concentration of 0.36 per cent produced a 35 per cent decrease in serum glutamic pyruvic transaminase (SGPT). It is concluded that deuteration of volatile anesthetics changes their metabolism, in most cases producing decreases in metabolism. This effect may lessen the organ toxicity believed to occur with some of these anesthetics.


Dose-response and plasma concentration-response relationships of pancuronium in man.

The dose-response and plasma concentration-response relationships for pancuronium in man were studied during its intravenous administration to eight patients at a rate of 1.62 microgram/kg/min. The (log) dose-response relationships resulted in a sigmoid curve that was linear in its central range. At 20, 50 and 80 per cent paralysis the cumulative dosages (mean +/- SEM) were 0.04 (+/- 0.01), 0.06 (+/- 0.01), and 0.08 (+/- 0.02) mg/kg, respectively. Administration of pancuronium, 56 microgram/kg, to another 12 patients at a more rapid rate resulted in a maximum intensity of blockade of more than 50 per cent. The (log) plasma concentration-response curve was not parallel to the dose-response curve, with mean (+/- SEM) concentrations at 20, 50 and 80 per cent paralysis of 0.21 (+/- 0.04), 0.25 (+/- 0.04), and 0.30 (+/- 0.04) microgram/ml, respectively during the onset of paralysis. Following cessation of the infusion, plasma concentrations of pancuronium were usually lower for the same intensity of paralysis. Using data for the entire response range during recovery from paralysis, the mean effective plasma concentration of pancuronium for a 50 per cent response was 0.20 microgram/ml. Recovery from blockade to 95 per cent paralysis (5 per cent of control twitch height) was associated with a plasma concentration of 0.25 microgram/ml, a value in agreement with plasma concentrations obtained following a single bolus administration of pancuronium, 6 mg, to 30 patients. For 27 patients the rate of decline of paralysis from 80 to 20 per cent showed a highly statistically significant relationship to the apparent rate of decline in the plasma concentrations of pancuronium.


Plasma concentrations of pancuronium and neuromuscular blockade after injection into the isolated arm, bolus injection, and continuous infusion.

To establish whether the plasma concentration of pancuronium reflects magnitude of neuromuscular blockade, the authors determined times of recovery from neuromuscular blockade and associated plasma concentrations following equipotent doses of pancuronium using three methods of pancuronium administration: the isolated-arm technique in conscious volunteers (n = 4), and the bolus intravenous injection (n = 7) and continuous-infusion methods (n = 3) in anesthetized patients. Although maximum depressions of twitch tension were similar (85 +/- 11,91 +/- 6, and 92 +/- 4 per cent, respectively) with the three techniques, times to recovery from neuromuscular blockade differed significantly, being 10 +/- 2 min with the isolated-arm technique, 23 +/- 7 min with the bolus-injection technique, and 46 +/- 5 min with the continuous-infusion method. The plasma concentration of pancuronium necessary for neuromuscular blockade was least with the isolated-arm technique and greatest with continuous infusion. At 25 and 75 per cent recovery, mean plasma concentrations were 0.07 +/- 0.01 and 0.04 +/- 0.01 microgram/ml in the isolated arm; 0.13 +/- 0.04 and 0.09 +/- 0.02 microgram/ml after bolus injection, and 0.20 +/- 0.04 and 0.11 microgram/ml during continuous infusion, respectively. It is concluded that the relationship between plasma concentration of pancuronium and magnitude of neuromuscular blockade depends on the method of pancuronium administration.


Hypertension during anesthesia on discontinuation of sodium nitroprusside-induced hypotension.

The authors had observed that on intraoperative discontinuation of sodium nitroprusside being administered to induce hypotension, mean arterial pressure increased to above the pre-hypotension level. Twelve patients who recieved hypotensive anesthesia for surgical correction of cerebral aneurysms were studied to evaluate the role of the renin-angiotensin system in this phenomenon. In the awake state, mean arterial pressure was 100 +/- 2 torr and plasma renin activity 3.0 +/- 0.1 ng/ml/hr. Thirty minutes after the establishment of stable halothane-nitrous oxide anesthesia, mean arterial pressure decreased to 85 +/- 1 torr and plasma renin activity increased to 4.4 +/- 0.1 ng/ml/hr. No appreciable change in either occurred over the next two hours of operation. During sodium nitroprusside-induced hypotension, mean arterial pressure decreased to 49 +/- 2 torr and plasma renin activity increased to 15.2 +/- 0.2 ng/ml/hr. Thirty minutes after discontinuation of sodium nitroprusside administration, mean arterial pressure increased to 112 +/- 2 torr, which was not only higher than the prehypotension level, but also significantly higher than that recorded in the awake state. Plasma renin activity at that time was 10.9 +/- 0.1 ng/ml/hr. As the half-life of plasma renin is 15 min, the data suggest that the persistently increased plasma renin activity is probably responsible for the increase of arterial pressure following sodium nitroprusside-induced hypotension.


Enflurane requirement and ventilatory response to carbon dioxide during lidocaine infusion in dogs.

Arterial plasma lidocaine concentration of 1 to 3.5 microgram/ml produced dose-related decreases in enflurane requirement (MAC) ranging from 15 to 37 per cent in dogs. The ventilatory responses to carbon dioxide at comparable depths of anesthesia with enflurane alone and the enflurane-lidocaine combination were measured in each animal and compared. With both anesthetic regimens there were increases in resting arterial carbon dioxide tension (mean maximal increase = 18 torr) and a 69 per cent decrease in the slope of the ventilatory response as depth of anesthesia increased. The effect of the drug interaction appears to be additive, since the ventilatory depression produced by the enflurane-lidocaine combination was no greater than that produced by enflurane alone at equivalent levels of anesthesia.


Edrophonium antagonism of pancuronium-induced neuromuscular blockade in man: a reappraisal.

The ability of edrophonium to reverse the nondepolarizing neuromuscular blockade produced by pancuronium was studied in 40 adult patients during light nitrous oxide--enflurane anesthesia. Antagonism of paralysis was attempted when the train-of-four fade ratio had spontaneous recovered in various extents. Edrophonium was administered in incremental doses intravenously either until the fade ratio increased to 0.70 or more or until the total dose of drug amounted to 0.5 mg/kg. All patients who had spontaneous recovery of train-of-four fade ratios to at least 0.10 had adequate reversal with edrophonium. When the train-of-four count was three or fewer visible twitches, the response to endrophonium was unpredictable. No evidence of recurarization was seen.


[Helminth fauna of Syrian cattle].

In this work the stomach and the small intestine of 34 and the large intestine of 4 more cattle were examined. 91,17% of the examined cattle (31 in 34 animals) had infected the stomach and/or the small intestine by parasites. 14 kinds of nematodes were found. The average intensity of infection of the stomach was higher than that of the small intestine. With the exception of higher infection in 3 stomachs and 2 small intestines the intensity of infection in all other cases was from small to medium in number. In contrast to this the frequency of infection was higher in small intestines than in stomachs.--The frequency of the found nematodes was: Ostertagia ostertagi 61,76%, Cooperia oncophora 61,76%, Cooperia punctata 47,05%, Trichostrongylus axei 41,17%, Cooperia zurnabada 38,23%, Bunostomum phlebotomum 20,58%, Haemonchus contortus 17,64%, Trichostrongylus vitrinus 11,76%, Skrjabinagia lyrata 5,88%, Trichostrongylus colubriformis, Trichostrongylus longispicularis, Parabronema skrjabini and Toxocara vitulorum each 2,94%.--According to the accessible literature Skrjabinagia lyrata, Ostertagia ostertagi, Trichostrongylus longispicularis, Cooperia punctata, Cooperia zurnabada, Bunostomum phlebotomum and Trichuris discolor were first found in Syrian ruminants. The helminths of Syrian ruminants which have become known until today are tabulated.


[Dipteran fauna of zoological preparation and veterinary postmortem rooms].

Zoological preparation rooms (P) and post-mortem rooms (S) constitute an environment for the spread of infection in areas of human habitation. In the absence of fly screens on the windows they are often invaded by Diptera which after landing on the frequently infested animal material leave again and become potential transmitters of disease in adjoining human living quarters. A large number of the 241 species of Diptera from 37 families identified in the P/S are regarded as potential transmitters. But suitability as transmitter is also potentially possible for an appreciable part of the remaining species. Field investigations over 20 years with various bait traps, e. g. fresh and decaying meat, excrements, human and animal food, have shown that many of these species observe sequences of substrate visitations similar to those Diptera identified in the literature as transmitters of disease. Should this assumption be confirmed the number of Diptera species which have to be considered as agents for the spread of disease would be enlarged within the environment of contamination P/S.--The results obtained in P/S constitutes an addition to the material so far worked out for the dipterology of human habitation. This should serve as background for further selective, microbiological and medical research on the role of Diptera as transmitters of disease.


[Unusual xiphidiocercaria from Ampullaria canaliculata with reference to Travtrema stenocotyle].

In overflowed areas from the Lujan-River near Zelaya, province of Buenos Aires, Argentina, a xiphidiocercaria with stenostome excretory system and 2 [(4 + 4 + 4) + (4 + 4 + 4 +)] = 48 flame cells was found in Ampullaria canaliculata. The cercaria encyst experimentally in the skin and internal organs of tadpoles. Natural infections were found in Hyla pulchella. The metacercaria, excepting the excretory system, is similar to Travtrema stenocotyle Cohn, 1902 from snakes.--In Leimadophis poecilogyrus 4 Trematode specimens were found and provisionally classified as Travtrema stenocotyle. A revision of the excretory system of Travtrema stenocotyle is suggested.


[Bychovskij's chief principles of Monogenea classification].

B. E. Bychovskij used the type of the adhesive structures and the formation of larvae as the basis of dividing Monogenea into groups. Using these principles he divided this class in two subclasses. Recent data confirm his chief statements.


Fine structure of digital vascular lesions in Raynaud's phenomenon and disease.

The ultrastructural changes in the vessels of the fingertips of patients with Raynaud's phenomenon or disease, with or without scleroderma, are described for the first time. Fingertip specimens were taken by punch biopsy. The light microscopic changes, including segmental vasculitis, fibrinoid degeneration of capillaries, and involuntary regression of glomus bodies explain the reduced digital blood flow associated with Raynaud's disease and phenomenon. The moment-to-moment digital blood flow, recorded rheoplethysmographically, was low when the patient was in a comfortable environment and was increased in a hot environment. This result substantiates the therapeutic importance of reflex vasodilatation. These findings correlate well with the ultrastructural changes in capillaries, including multiple cytoplasmic folds in endothelial cells, abundant intracytoplasmic filaments, and unusual incorporation of collagen fibrils in the basement membrane. These changes must influence nutritional and thermoregulatory function of the digital blood vessels.


Effect of gonadectomy on isoproterenol-induced myocardial infarction.

Adult male and female Sprague-Dawley rats were subjected to an isoproterenol-induced myocardial infarction. Six weeks before the induction of myocardial infarction, some of the animals had been orchiectomized or ovariectomized. The animals were autopsied at regularly timed intervals on days 1, 2, 3, 8, and 15 after myocardial infarction. The gonadectomized animals manifested less severe untoward changes, survived in greater numbers, and experienced superior repair of their damaged hearts. Circulating levels of enzymes (e.g., CPK, GOT, GPT, and LDH), lipids, glucose, and BUN rose and fell during the acute necrosis and repair phases with distinct differences between the intact and castrated animals. Reciprocal changes in the weight of the adrenal and thymus glands, coupled with dynamic changes in circulating corticosterone levels, reflected marked temporal changes in the spectrum of adrenal steroids being secreted, as well as gonadal hormone mediated changes affecting adrenocortical function. The implications of these findings are that adrenocortical, androgenic, and estrogenic hormones condition the nature of the pathophysiologic response to acute myocardial infarction in rats.


Value of treadmill exercise testing in patients with complete bundle branch block.

Exercise electrocardiography and selective coronary arteriography was performed in 24 consecutive patients with complete bundle branch block. The criteria for a positive exercise electrocardiogram (E-ECG) were a 1 mm depression or elevation in the J point from the control state, as well as in the ST-segment measured at 0.04 seconds from the J point. Eleven of 12 patients with complete left bundle branch block had a positive E-ECG. Nine of them had normal coronary arteriograms, except one with less than 50% lesions in two arteries. Two patients had severe three-vessel disease. Only one patient had a true negative exercise test. No patient had a false negative test. Nine of 12 patients with complete right bundle branch block had a positive E-ECG. One of these 9 had minimal nonobstructive disease, while the other 8 had severe two- or three-vessel coronary artery disease. Three of the 12 right bundle branch block patients had a negative E-ECG. Two of them had a true negative exercise test, and one a false negative test. Because of a high incidence of probably false positive results, E-ECG appears to be unreliable in detecting coronary artery disease in patients with complete left bundle branch block. But it can provide useful information in the noninvasive evaluation of coronary artery disease in patients with complete right bundle branch block.


Inhaled atropine in asthma.

Ten adult asthmatics inhaled atropine and isoproterenol to determine the site of action in the airways and relative effectiveness of the two drugs. The two agents were equal in their effect on lung volumes and airway resistance but isoproterenol produced significantly better flows. Atropine was shown to be an effective bronchodilator with a predominant site of action in large airways. The authors believe atropine and atropine derivatives deserve ongoing investigation, especially regarding potential side effects of retarding mucociliary clearance and the clinical significance of apparent failure to dilate small airways.


Relationship between response to exercise and allergy in patients with cystic fibrosis.

Responses to treadmill exercise of 36 patients with cystic fibrosis were studied to evaluate their usefulness in identifying those with atopy. Ten of 36 patients with cystic fibrosis (28%) had an abnormal response to exercise but had no more frequent atopic characteristics than those who had normal exercise responses. Response to treadmill exercise alone cannot identify patients with atopic disease among those with cystic fibrosis.


Treatment of active herpes virus infections with influenza virus vaccine.

A system for treating active virus infections with very small, precisely determined doses of specific killed-virus vaccine is described. Results indicate that the discomforts of influenza and herpes virus infections usually disappear within 30 minutes after injection of the vaccine. The relief occurs during testing and repeated subcutaneous injections produce rapid healing.


Assessment of a technique for scintigraphic monitoring of pulmonary aspiration of gastric contents in asthmatics with gastroesophageal reflux.

Ten asthmatics with gastroesophageal reflux had scintigraphic evaluation of gastropulmonary aspiration. Five mCi of Tc99m sulfur colloid diluted in 50 ml of isotonic saline were administered by nasogastric tube at bed time and the lungs were imaged the following morning. Imaging in 20 studies yielded no evidence of gastropulmonary aspiration. Scintigraphic evaluation has previously been reported to demonstrate gastropulmonary aspiration in some patients with gastroesophageal reflux and pulmonary disease. This study indicates that the technique may lack adequate sensitivity or that gastropulmonary aspiration in asthmatics with gastroesophageal reflux occurs in only a small subgroup of these patients or at infrequent intervals and is difficult to detect.


North American pollinosis due to insect-pollinated plants.

In warmer regions of North America many newly introduced plants are cultivated widely and others are becoming aggresive naturalized weeds. A large number are insect-pollinated and shed considerable quantities of airborne pollen. Levels of allergenicity based on skin test data, numbers of patients having immediate hypersensitivity and localities where airborne pollen grains have been identified are presented for each genus of entomophilous plants considered incitants of pollinosis. Among the most relevant are Acacia, Brassica, Citrus, Ligustrum, Olea and Schinus.


Immunoglobulins and hyposensitization for allergy.

The premise that protracted stimulation of the human immune system might be involved in the induction of malignant immunocytopathies is scrutinized. Studies of the serum immunoglobulins of 313 patients who had been hyposensitized for allergy are compared with those of 138 nonallergic and 189 allergic individuals not subjected to this therapy. Critical historical data in all groups are also evaluated. The investigators concluded that, as far as the parameters studied, there were significant differences in the mean total immunoglobulin G levels in allergic hyposensitized persons compared with the non-allergic control group. It involved a depression of the serum IgG concentration and related to the length of the desensitization program and to whether it was continuous or interrupted. One evolving monoclonal immunocytopathy, etiology of which has not been established, was encountered during the period of study.


The effect of cimetidine on the immediate cutaneous response to allergens.

The effects of an H2 antagonist cimetidine on the immediate cutaneous response to timothy or ragweed extract were evaluated. Cimetidine had no effect on the immediate cutaneous response to either allergen. These findings suggest that cimetidine need not be discontinued prior to allergy skin testing.


Quantitative effect of theophylline anhydrous on exercise-induced asthma after maximal physical effort.

The quantitative effects of theophylline anhydrous upon exercise-induced asthma (EIA) were evaluated in asthmatic children. Theophylline inhibits EIA after maximal physical effort, increases tolerance to exercise and exerts a greater inhibitory effect upon larger than smaller airways. Its inhibitory effect seems not to be related to plasma theophylline levels.


Suppression of mitogen-induced, cell-mediated cytotoxicity by prostaglandin F2 alpha in bronchial asthma.

Prostaglandin F2 alpha (PGF 2 alpha) has a bronchoconstrictive effect on the smooth muscles of the bronchial tree, while a prostaglandin of the E series (PGE) provokes bronchodilatation in bronchial asthma (BA). The PGE series can suppress cytotoxic T lymphocytes and it was expected that PGF2 alpha would have the opposite effect, since similarities exist between microvilli of circulating blood lymphocytes and bronchial smooth muscles. Pharmacological modulation of lymphocytes, using a mitogen-induced, cell-mediated cytotoxicity assay (MICC), showed that PGF2 alpha suppresses cytotoxic activity of lymphocytes in BA patients and normal controls. This observation provides evidence that the spasmogenic effect of inhaled PGF2 alpha on the smooth muscles of the airways does not correspond to expected increased cytotoxicity of the circulating blood lymphocytes in vitro.


On the correlation between rast and the allergy intradermal test.

RAST and intradermal testing correlated reasonably well for untreated patients for ragweed and molds and in treated patients for trees. Capillary blood was found to be comparable to venous blood as a source for RAST for ragweed and mixed grasses.


Characteristics of the asthmatic airway response to inhaled diluent.

This study was designed to analyze the airway response to an aerosolized diluent in patients with asthma. Fifty percent of the patients responded to diluent with less than a 10% variation from baseline (non responders), but 20% of the patients responded with more than a 25% difference from baseline (responders). This study stresses the need for control data with diluent prior to bronchial challenge with a provocative agent.