Gastric abnormalities in humoral immune deficiency syndromes.

Patients with late-onset hypogammaglobulinaemia have a very high risk of developing gastric cancer. In such patients there is a high frequency of atrophy of the gastric mucosa. This is reflected in low gastrin content of the antral mucosa, low serum pepsinogen A level and pepsinogen A/C ratio, and reduced serum gastrin secretion in response to bombesin stimulation. There is no evidence to support a role of Helicobacter pylori infection in the aetiopathology of these gastric abnormalities, although prior infection cannot be excluded with certainty. Since patients with early-onset hypogammaglobulinaemia and X-linked agammaglobulinaemia do not show this increased frequency of gastric abnormalities, it is unlikely that the immunoglobulin deficiency per se is responsible for the development of the gastric abnormalities found in patients with late-onset hypogammaglobulinaemia. Because of the very high risk of gastric cancer, regular endoscopic screening is warranted in patients with late-onset hypogammaglobulinaemia.


Laparoscopic gastrointestinal and gallbladder surgery: will the promise be fulfilled?

The results of the first 181 consecutive patients who underwent laparoscopic cholecystectomy and 12 patients who underwent laparoscopic colon resection in our hospital are described. Our results show that laparoscopic cholecystectomy has proved to be the standard surgical procedure for treating gallbladder disease. The place of laparoscopic surgery in the treatment of other abdominal diseases is less clear. Our results in laparoscopic colon surgery indicate that a laparoscopic approach in segmental colon resection is feasible. The operation time is long, however, expressing the long learning curve for the operating team, as well as the technical difficulties encountered with this minimal invasive method. On the other hand, it has been proved that large abdominal operations can be performed via the laparoscope. By improving the laparoscopic instruments and increasing the laparoscopic surgeon's experience, further application of this method in gastrointestinal surgery may be expected. Surgeons should, however, be aware of the long learning curve involved in advanced laparoscopic surgery.


A decade of experiences with radioimmunoassays for cholecystokinin in The Netherlands.

The radioimmunologic determination of cholecystokinin (CCK) has proved to be notoriously difficult. This is due to the specificity of antibodies, preparation of radiolabeled CCK and low CCK concentrations in human plasma. About 10 years ago we succeeded in developing two highly sensitive region-specific radioimmunoassays for CCK. Antibody T204 binds to the sulfated tyrosine region of CCK, while antibody 1703 reacts with biologically active molecular forms of CCK containing at least 14 amino acid residues. Both antibodies are devoid of significant cross-reaction with gastrin. By means of these two radio-immunoassays CCK concentrations were measured in both tissue and plasma of various species, including man. In addition, the molecular forms of CCK in tissue and plasma were characterized. These CCK assays were used to study the mechanism of CCK secretion. It appeared that digested rather than intact protein and fat stimulated CCK release from the small intestine. The physiologic and pathophysiologic role of CCK in humans was studied using CCK radioimmunoassays and specific CCK-receptor antagonists. CCK was found to play an important role in pancreatic enzyme secretion, gallbladder contraction, and gastrointestinal motility but possibly also in pancreatic carcinogenesis and regulation of satiety and satiation.


Pharmacokinetics of ranitidine in a homogeneous population of intensive care unit patients during intermittent and continuous administration.

The pharmacokinetics of ranitidine during two different modes of intravenous administration was studied in a homogeneous group of postoperative intensive care unit patients (n = 18). Patients at risk of developing stress-related lesions were randomized to receive repeated injections, 50 mg every 6 h (group A), or a continuous infusion, 50-mg bolus followed by 0.125 mg/kg/h (group B). Before treatment all patients received a single 50-mg ranitidine dose. Serum ranitidine concentrations were measured for 12 h after the single dose and during the treatment period, to calculate individual pharmacokinetic variables. From the single-dose study the calculated half-life, volume of distribution, and clearance were 3.14 +/- 0.61 h, 1.45 +/- 0.42 l/kg, and 0.40 +/- 0.14 l/kg/h for group A and 3.33 +/- 1.08 h, 1.16 +/- 0.20 l/kg, and 0.35 +/- 0.21 l/kg/h, for group B, respectively. Ranitidine pharmacokinetics after the single dose was comparable in the two groups. No statistically significant differences could be detected between the ranitidine pharmacokinetics after the first single dose and the multiple dose or continuous infusion.


Indications for surgical treatment of pancreatic cancer.

The best chance for cure of pancreatic cancer is surgical resection. This is also possible in case of adjacent organ involvement of, for example, duodenum, portal vein, or colon. Pancreatic tumours may develop to a large size without developing metastases. Irresectable tumours without distant metastases can successfully be treated with radiotherapy and 5-fluorouracil and, in some cases, be resected during a second-look operation. Thus there is no contraindication for laparotomy in case of large size. Preoperatively estimated size of the tumour is not of prognostic value for resection. Altogether, laparotomy is contraindicated only in case of distant metastases and high operative risk.


CD4 antibody treatment in Crohn's disease.

Immunologic changes may play a role in the pathogenesis of Crohn's disease. Whether these changes are the primary cause of the disease or secondary to the inflammatory response remains unknown. Activated T helper cells probably play a pivotal role in Crohn's disease, although no causative antigen has been identified. Possible targets for immunomodulating therapy should include neutralization of the antigens, deletion of reactive activated T cells or, less specifically, interference with the antigen-presenting process. New, humanized, monoclonal antibodies that interfere with the antigen-presenting process are now available for clinical investigation. In particular, CD4 antibody treatment seems of interest, in view of the predominant role of T cells in Crohn's disease. Finally, because tumor necrosis factor is necessary for granuloma formation, inhibition of this factor may be expected to improve disease activity in Crohn's disease.


Primary bile acid malabsorption: a pathophysiologic and clinical entity?

Primary bile acid malabsorption is defined as chronic diarrhoea with bile acid malabsorption of unknown cause and a symptomatic response to cholestyramine. Convincing evidence of the proposed pathophysiology--a defect of the active bile acid absorption in the distal ileum--has never been substantiated. We found no evidence of a bile acid transport defect across the ileal brush border membrane in 10 patients with primary bile acid malabsorption; moreover, transport was significantly higher than in a control group. In the patients with primary bile acid malabsorption the estimated bile acid pool was significantly larger than in a control group and in a group of patients with ileal disease. In addition, the oro-anal transit time of radiopaque markers was shorter in the primary bile acid malabsorption group than in both other groups. This suggests that the bile acid pool size as well as intestinal motility could play a role in the pathophysiology of primary bile acid malabsorption.


Primary sclerosing cholangitis. An unresolved enigma.

Primary sclerosing cholangitis (PSC) is a disease of the bile ducts which frequently is associated with inflammatory bowel disease. The disease is characterized by stenoses and saccular dilatations of the intra- and/or extra-hepatic bile ducts. Endoscopic retrograde cholangiography is the mainstay of diagnosis of this disease. A liver biopsy gives additional information and is particularly useful to rule out secondary cirrhosis. In a series of 50 patients the 5-year survival was 85%. The etiology is unknown, but in addition to inflammatory bowel disease the disease is associated with the autoimmune haplotype HLA-A1, B8, and DR3. Antibodies to perinuclear antigens in leukocytes are present in 65% of patients with PSC. Ursodeoxycholic acid therapy causes an improvement of symptoms and a decrease of elevated liver enzyme values. There are no drugs as yet with a proven effect on fibrosis or cirrhosis in this disease. Liver transplantation in this disease has a reported 4-year survival of 88%.


Complications in obstructive jaundice: role of endotoxins.

Surgical treatment of patients with obstructive jaundice is associated with a high postoperative morbidity and mortality. A correlation was suggested between endotoxins and the observed complications. The mechanism by which endotoxins affect the negative outcome in operated jaundiced patients was, however, not clear, nor was the mechanism of clinically used preventive treatments. Several experiments were therefore performed in rats with biliary obstruction, to investigate whether and how endotoxins are active. The role of endotoxins was studied in a model in which endotoxins were absent. In germfree rats (free of bacteria and thus of endotoxin) the effect of biliary obstruction was studied and compared with biliary obstruction in conventional rats. To substantiate further the role of endotoxin, anti-endotoxin treatments (oral lactulose or internal drainage) were tested in rats with obstructive jaundice undergoing a severe surgical trauma. It is shown that endotoxins are responsible for complications (suppression of cellular immunity, kidney function, mortality) and that these complications can be prevented with an anti-endotoxin treatment. These results may have implications for preoperative treatment of jaundiced patients.


New developments in hepatitis C.

Since the detection of hepatitis B virus (HBV) in the 1960s and hepatitis A virus in the 1970s, a considerable proportion of infections of (probably viral) hepatitis could not be classified. About 90% of transfusion-related hepatitis was identified as non-A/non-B. In 1988 investigators from the Chiron Company (USA) detected the non-A, non-B agent and named it hepatitis C virus (HCV). An anti-HCV antibody assay (ELISA) and subsequently confirmation tests (immunoblot and polymerase chain reaction) were developed. HCV infection results in a chronic carrier state of the virus in about 80%. Almost all HCV carriers have, irrespective of their liver function tests, histologic signs of chronic hepatitis and/or liver cirrhosis. Chronic HCV infection is, like HBV, also associated with the development of hepatocellular carcinoma. Most HCV carriers are infected by parenteral routes (intravenous drug use, blood transfusion, tattooing). Intravenous drug users and haemophilia patients have the highest risk (80-90%) of becoming infected. Sexual and perinatal transmission does not play an important role in spreading the infection. Antiviral therapy (alpha-interferon) in patients with chronic hepatitis C will normalize liver function tests in about 25% of the cases, but it is unclear if the HCV carrier state will disappear and if liver cirrhosis will be prevented. At present no specific immunoglobulin or vaccine preparations are available to prevent the HCV infection.


Chemotherapy for gastrointestinal cancer: new hopes or new disappointments?

Since the end of the eighties relevant progress has been made in the treatment of gastrointestinal tract cancer, as well in advanced disease as in the adjuvant setting. The neoadjuvant treatment of localized esophageal and gastric cancer is of high interest, and especially the adjuvant treatment of colorectal cancer provides a realistic hope for further progress in the years not too far ahead. Results of recent studies with implications for future trials are discussed.


Feeding via nasogastric tube or percutaneous endoscopic gastrostomy. A comparison.

When a patient needs enteral feeding, there are two methods to administer the nutrition. The method most used is the nasogastric tube (NGT), although in the literature little is published about the advantages and complications of the NGT. The second method is percutaneous endoscopic gastrostomy (PEG). A prospective randomized trial was started, and so far 90 patients have entered the study (46 NGT and 44 PEG). In four patients it was not possible to insert the NGT, and in three patients it was impossible to place the PEG. In both groups 6.5% aspiration was found. Nasal decubitus and swallowing problems were seen in 13% and 17%, respectively, in the NGT group. Intraperitoneal bleeding and abdominal pain were found in 2% and 11%, respectively, in the PEG group. Fixation of the patients was needed in 7% of the PEG and 22% in the NGT group. In eight patients in the NGT group the feeding had to be stopped owing to problems; in none of the PEG group was this necessary. The nursing staff awarded marks to each patient on a scale of 5 for the convenience of care (very good, 1; very bad, 5). This resulted in a mean score of 2.6 in the NGT and 2.0 in the PEG group. The score given by the patients was 2.3 in the NGT and 1.8 in the PEG group. There seems to be a clear preference for the PEG as a method for enteral nutrition.


Gastric secretory abnormalities in duodenal ulcer: primary or secondary to Helicobacter pylori infection?

Hypersecretion of gastric acid, gastrin, and pepsinogen are considered to be causally related to duodenal ulcer diathesis. Until recently, these abnormalities have been considered to be primary and largely genetically determined. However, Helicobacter pylori infection has been shown to be responsible for several of the abnormalities of gastric secretion in duodenal ulcer. H. pylori infection is not only associated with chronic active inflammation but also with a reduction of somatostatin producing D-cells and somatostatin concentrations in the gastric mucosa. The reduced inhibitory action of somatostatin on the secretion of gastric acid, gastrin, and pepsinogen may be responsible for the hypersecretory state of the stomach in duodenal ulcer. These recent findings have drastically changed our understanding of the pathogenesis of duodenal ulcer.


Seroepidemiological studies of malaria in different endemic areas of Indonesia.

A total of 618 sera from inhabitants living in various endemic areas in Indonesia were examined for IgG against Plasmodium falciparum utilizing young trophozoites and mature schizonts as antigens by the method of ELISA and IFAT. In general, antibodies against trophozites (RESA) based on ELISA and antibodies against schizonts based on IFAT showed a correlation of malarial antibodies with the level of endemicity of the area examined. Anti-RESA antibody, detected either by ELISA or IFAT was more pronounced in the aparasitemic group compared to the parasitemic group. On the contrary, anti-schizont antibody measured by IFAT was more pronounced in the parasitemic group. Malarial antibody levels against the schizont-merozoite fraction of P. falciparum as assayed by ELISA appeared to develop more slowly compared to levels based on IFAT.


Epidemiology and control of malaria in Malaysia.

In spite of more than 30 years of control activities, malaria continues to be the most important parasitic infection in Malaysia, accounting for 39,189 confirmed cases in 1991, giving an annual parasite incidence rate of 2.2 per 1,000 population. Some factors contributing to the continued transmission of malaria are the development of drug resistant Plasmodium falciparum, changes in vector behavior, and ecological changes due to socio-economic reasons. Malaria parasite rates are higher among the Aborigines, land scheme settlers and those in intimate contact with the jungle, like loggers. There has been no substantial change in the proportion of the three common malaria species responsible for infections, P. falciparum, P. vivax, P. malariae and mixed infections accounting for about 70%, 28%, 1% and 1%, respectively of all infections. Drug resistant P. falciparum is unevenly distributed in Malaysia, but based on clinical experience and in vitro drug sensitivity studies, chloroquine resistance is frequently encountered. There has been clinical and laboratory evidence of resistance to sulfadoxine/pyrimethamine combination as well as quinine, but all these have so far been successfully treated with a combination of quinine and tetracycline. The eradication of the disease is impossible in the near future but there is confidence that with better surveillance techniques and the use of alternative control measures like permethrin impregnated bed-nets to complement existing ones, the target of bringing down the annual parasite incidence to 2 per 1,000 population during the Sixth Malaysian Plan period (1991-1995) can be achieved.


Intestinal protozoan infections in Malaysia.

Intestinal protozoa are found in all communities in Malaysia and among all ethnic groups. Prevalence of intestinal protozoa is not affected by ethnicity but by living conditions. Communities with both basic amenities of safe water supply and proper toilets have lower prevalence than those with one or none of the amenity. Cryptosporidium is an important intestinal protozoon in Malaysia and should be included in future field and laboratory studies and also in laboratory diagnosis for pathogens. Much interest will be centered on Blastocystis hominis in future studies in view that it may be a cause of diarrhea.


Immunological studies on some bacterial and parasitic diseases in Thailand.

Over the past two decades a wide range of immunological studies have been carried out on organisms responsible for causing serious bacterial and parasitic diseases in Thailand. Particular emphasis has been placed on cholera, where investigations have been directed towards vaccine development and rapid diagnosis and on diagnosis of typhoid and enterotoxigenic Escherichia coli. In the area of parasitic diseases emphasis has been directed especially to immunodiagnosis of helminthic diseases, including gnathostomiasis, paragonimiasis, opisthorchiasis, strongyloidiasis and trichinellosis. These studies are reviewed in this report.


Drug resistant malaria, with special reference to Thailand.

Drug resistance of malaria parasites is a major problem confronting efforts to treat and control malaria. Starting with chloroquine, the emergence of resistance to other drugs has led to multi-drug resistance patterns that pose increasing threats for the future. This report reviews work carried out over the past decades at the Hospital for Tropical Diseases, Bangkok, which monitors patients from many areas, including the Thai-Cambodian border, which harbors the world's most severe multi-drug resistant Plasmodium falciparum.


Global malaria challenge: the Amsterdam summit.

On 26-27 October 1992 the World Health Organization convened a global Ministerial Conference on Malaria in Amsterdam to draw up a global strategy for renewed attack on malaria, in view of the deteriorating situation in the control of this disease in many parts of the world. This report summarizes the key points of the strategy and the Declaration emanating from this crucial assembly of nations, which it is hoped will lead to increased tangible support nationally, from international agencies and from bilateral agreements for greatly improved programs of malaria control.


Economics and tropical diseases: a research agenda using schistosomiasis as an example.

There is a growing interest in health economics in developing countries. In this paper, some of the economic literature concerning schistosomiasis is reviewed and a set of economic questions is derived which could form the basis of a broad research agenda for tropical diseases. The major criterion used to identify research issues is that they should be of practical value to control programs.


Thalassemia in SouthEast Asia: problems and strategy for prevention and control.

In Southeast Asia alpha-thalassemia, beta-thalassemia, hemoglobin (Hb) E and Hb Constant Spring are prevalent. The gene frequencies of alpha-thalassemia reach 30-40% in Northern Thailand and Laos. beta-Thalassemia gene frequencies vary between 1 and 9%. Hb E is the hallmark of Southeast Asia attaining a frequency of 50-60% at the junction of Thailand, Laos, and Cambodia. Hb Constant Spring gene frequencies vary between 1 and 8%. These abnormal genes in different combinations lead to over 60 different thalassemia syndromes. The four major thalassemic diseases are Hb Bart's hydrops fetalis (homozygous alpha-thalassemia 1), homozygous beta-thalassemia, beta-thalassemia/Hb E and Hb H diseases. The molecular basis of most of these abnormal genes have been recently described. Therefore, it is possible to set a strategy for prevention and control of thalassemia which includes population screening for heterozygotes, genetic counseling and fetal diagnosis with selective abortion of affected pregnancies.


Towards a malaria vaccine: riding the rollercoaster between unrealistic optimism and lethal pessimism.

Activity in many laboratories over the past decade has resulted in many vaccine candidates nearing clinical trials. These include several antigens from the sporozoite stage; merozoite surface antigens MSA1 and MSA2, RESA, the rhoptry proteins RAP-1 and RAP-2 from the asexual blood stage; the pfs25, pfg45 and pfg230 from the ookinete and gamete stages. This progress in the identification of potential vaccine candidates now highlights a series of scientific, developmental, economic and operational problems the solutions to which will be as critical to the development of a vaccine as the cloning and expression of parasite genes.


Neurological complications of malaria.

This paper reviews the neurological complications of malaria. Cerebral malaria, the acute encephalopathy which complicates exclusively the infection by Plasmodium falciparum commonly affects children and adolescents in hyperendemic areas. Plugging of cerebral capillaries and venules by clumped, parasitized red blood cells causing blood sludging in the capillary circulation is one hypothesis to explain its pathogenesis. The other is a humoral hypothesis which proposes a nonspecific, immune-mediated, inflammatory response with release of vasoactive substances capable of producing endothelial damage and alterations of permeability. Cerebral malaria has a mortality rate up to 50%, and also a considerable longterm morbidity, particularly in children. Hypoglycemia, largely in patients treated with quinine, may complicate the cerebral symptomatology. Other central nervous manifestations of malaria include intracranial hemorrhage, cerebral arterial occlusion, and transient extrapyramidal and neuropsychiatric manifestations. A self-limiting, isolated cerebellar ataxia, presumably caused by immunological mechanisms, in patients recovering from falciparum malaria has been recognized in Sri Lanka. Malaria is a common cause of febrile seizures in the tropics, and it also contributes to the development of epilepsy in later life. Several reports of spinal cord and peripheral nerve involvement are also available. A transient muscle paralysis resembling periodic paralysis during febrile episodes of malaria has been described in some patients. The pathogenesis of these neurological manifestations in malaria remains unexplored, but offers excellent perspectives for research at clinical as well as experimental level.


Importance of ecology in Aedes aegypti control.

Aedes aegypti is one of the world's most widely distributed mosquitos and is of considerable medical importance as a vector of dengue and yellow fever. Not surprisingly therefore there has been more written on its biology than any other mosquito. The present paper summarizes ecological studies undertaken on this vector, including those on pre-adult mortalities, life-tables, adult dispersal and survival rates. In discussing surveillance techniques it is pointed out there are still no reliable methods for monitoring adult populations. The importance of the resting habits of adults and house construction in insecticidal control of Ae. aegypti is discussed. The question is, have ecological studies and population modeling resulted in any more understanding of the epidemiology of dengue, or helped formulate better control strategies? The answer seems to be not usually, possible because there have actually been relatively few good ecological studies on Ae. aegypti. Although mathematical modeling indicates that better control might be achieved if it were directed at the larvae, not adults, this has not usually been taken into consideration by those engaged in control. There is clearly need for greater collaboration between those practicing control, and ecologists and modelers.


Iron status of pregnant Filipino women as measured by serum ferritin.

Iron status of pregnant women at different stages of pregnancy was evaluated by comparing values for hemoglobin (Hb), red cell indices, serum iron (SI), transferrin saturation (TS) and serum ferritin (SF) values with those of a group of non-pregnant women of comparable age and socio-economic status. Mean SF values on the second and third trimesters (9.3 +/- 2.60 ng/ml and 7.1 +/- 2.19 ng/ml) were significantly lower compared to that in the first trimester (22.6 +/- 2.20 ng/ml). These levels were also lower than that found in the non-pregnant controls. The trend was the same for TS. Hemoglobin levels of the pregnant subjects were significantly lower than those of the non-pregnant women. Prevalence of iron deficiency based on SF < 12.0 ng/ml and TS < 16.0% was highest at term and lowest during the first trimester indicating a decrease in iron stores as pregnancy progressed. Sensitivity for each of the iron parameters was computed, and it was found that for the diagnosis of iron deficiency in pregnant women, SF has a greater sensitivity than TS, SI, MCV and MCH.


Hypercalcemia in active pulmonary tuberculosis and its occurrence in relation to the radiographic extent of disease.

The prevalence of hypercalcemia in tuberculosis in Hong Kong and its occurrence in relation to the radiographic extent of disease were studied in 57 patients with sputum smear (n = 44) and/or culture positive (n = 13) pulmonary tuberculosis and in five patients with military tuberculosis prior to treatment. Only one (1.6%) patient had a corrected plasma calcium level above the reference range for our laboratory. There was a positive relationship between the corrected plasma calcium levels and the radiographic extent of disease (r = 0.37), p < 0.01). As the occurrence of hypercalcemia in tuberculosis is known to be influenced by the calcium intake, our finding of a low prevalence of "absolute" hypercalcemia in Hong Kong could be related to the low dietary calcium intake in these subjects.


Streptococcal throat carriage in school children with special reference to seasonal incidence.

A number of studies on throat carriage of beta hemolytic streptococci (BHS) carried out during the years 1972-90 in urban and rural school children from low socioeconomic groups in the age group of 5-15 years in and around Delhi showed an overall carriage rate of BHS varying from 12.2%-64.3% depending upon the season and number of swabs taken. Group A was found to be the most predominant serological group (31.1%-62.6%). The T-typability was found to be 98.2%. The most prevalent T-patterns observed during 1972-78 study were 3/13/B3264 followed by 5/11/12/27/44. A significant difference was observed in the prevalence of T-patterns during the study of 2,034 children from 1979-83 and 3,094 children from 1984-90. When the most prevalent T-patterns were found to be 5/11/12/27/44 followed by 3/13/B3264. The study of the school children from 1972-90 showed the isolation of BHS as well as significant predominance of GAS (p < 0.001) in winter months than summer months. There was no difference in the distribution of carriage of BHS and GAS amongst rural or urban school children. Since RF/RHD are illnesses which were often encountered in school children among socially and economically disadvantaged populations stronger support for streptococcal surveillance programs should be encouraged.


Pulmonary pathology in rabbits infected with the Baling and Koyan strains of Schistosoma malayensis.

Two distinct strains of Schistosoma malayensis exist in Malaysia (designated the Baling and Koyan strains). Both these strains show intraspecific variations in pathology (Greer et al, 1988). To evaluate the differences in the pulmonary pathology resulting from infections of the two different strains of Malaysian schistosome, a total of 20 experimental rabbits were infected, 10 each with cercariae of the Koyan strains. Pathological changes were studied over a period of 28 weeks. Granulomas in the lung occurring as a result of infection with the Baling strain were compared with those caused by infection with the Koyan strain. Although both strains produced parenchymatous and alveolar lesions, granulomas caused by the Baling strain of Malaysian schistosome were more numerous and larger (when comparing mean diameter as well as area of granuloma, p < 0.05). In addition, pulmonary vascular hypertensive changes were present in Baling strain infected rabbits. These comprised of pulmonary arteriolar endothelial swelling and damage, intimal elastosis and medial hypertrophy. Angiitis and pulmonary periphlebitis were also noted occasionally. In contrast, Koyan strain infection resulted in fewer and smaller granulomas. Pulmonary vascular changes were minimal.


Albendazole stimulates outward migration of Gnathostoma spinigerum to the dermis in man.

Human gnathostomiasis is characterized by space-occupying inflammatory lesions and/or hemorrhage as a result of the migration of, very often, a single larva of Gnathostoma spinigerum. Intermittent cutaneous migratory swellings occurring over years is the most common manifestation and the rare cerebral invasion may be fatal. There are currently no effective anthelminthics for this infection. During a double-blind randomized placebo control trial evaluating the efficacy of albendazole in cutaneous gnathostomiasis at a dosage of 400 mg twice daily for two weeks, it was observed that gnathostome larvae tended to migrate outward as a result of the treatment so that they could be recovered by excisional biopsy or by picking with a needle. In the placebo-treated group (N = 40), no such migration was observed during the 8,470 patient-days of follow-up while in the albendazole-treated group (N = 41) there was one worm in an excisional biopsy done on day 16 and two worms were removed from the skin by the patients themselves on days 8 and 0. Assuming that the period of drug exposure of the gnathostomes was the 14 days of albendazole administration plus another washout period of 7 days (equivalent to 20 half-lives of the active detectable metabolite), the total patient-days of albendazole exposure was 830. The rate of outward migration of gnathostomes in the drug treated group (3 per 830 patient-days) was significantly (p < 0.0001) higher than in the placebo group (0 per 8,470 patient-days).(ABSTRACT TRUNCATED AT 250 WORDS)


Problems in dengue control: a case study.

The control of dengue outbreak requires a multi-pronged effort by the various government agencies. It requires co-operation of the community in the control activities, strict adherence to existing control procedures and guidelines by health personnel, increased manpower where necessary and strengthening co-operation between various health agencies to prevent delay in instituting control measures.


IgM capture ELISA for detection of IgM antibodies to dengue virus: comparison of 2 formats using hemagglutinins and cell culture derived antigens.

The highly sensitive AFRIMS format IgM capture ELISA for the diagnosis of dengue virus infections requires the use of mouse brain derived hemagglutinins and consequently also the use of 20% acetone extracted normal human serum to eliminate high background. These reagents are not always easily available and we have thus compared the AFRIMS format with another published format which uses cell culture derived antigens (culture fluid, CF, format) in order to determine if it is reasonable to use cell culture derived antigens in situations where hemagglutinins and normal human serum are difficult to obtain. The study shows that using AFRIMS results as the reference point, the CF format described here has a sensitivity of 90% and a specificity of 96%.


Detection of circulating plasmodial antigens in human sera by sandwich ELISA with monoclonal antibodies.

Two monoclonal antibodies (MAbs), one produced against Plasmodium falciparum (PF-IG8) and the other against P. cynomolgi (PC-IE12) schizont antigens were used in a sandwich ELISA for the detection of circulating plasmodial antigens in sera of patients infected with either P. falciparum, P. vivax or P. malariae. The mean +/- SD optical density (OD) values for the normal control group using PF-108 and PC-1E12 were 0.351 +/- 0.036 and 0.205 +/- 0.044, respectively. Mean OD values for the three infected groups were found to be significantly higher than those of the normal control group for both MAbs. However, ELISA values for individual serum specimens did not correlate with the level of parasitemia in the infected blood. Using a cut-off point of mean OD +/- 3 SD of the normal control group as indicating a positive reading, the specificity of this assay with both MAbs was 100%. The sensitivity of the assay using PF-1G8 was 95% while that obtained with PC-1E12 was 98%.


Two-site pan-species monoclonal antibody ELISA for detection of blood stage malaria antigen.

A two-site pan-species monoclonal antibody sandwich ELISA (MAb-MAb ELISA) was developed to detect both Plasmodium vivax and P. falciparum antigens in whole blood impregnated on filter paper. In this assay, the plates were coated with pan-species MAb 3F9 and another pan-species MAb M26-32 conjugated with alkaline phosphatase was used for detection of bound antigen. The sensitivity of this assay was 5, 10 and 10 parasites per 10(6) erythrocytes for cultured P. falciparum, patient-derived P. vivax and P. falciparum, respectively. The coincidence rates for this assay were 93% (92/99) with healthy individuals and 93% (42/45) with microscopically confirmed vivax malaria cases. After two weeks treatment, 77.7% (14/18) of vivax malaria were still positive by this assay but with diminished level of reactivities [corrected].


Two-site sandwich ELISA for detection of Plasmodium vivax blood stage antigens using monoclonal and polyclonal antibodies.

Two systems of sandwich enzyme-linked immunosorbent assay (ELISA), a two-site monoclonal antibody sandwich ELISA MAb-MAb sandwich ELISA) and a two site polyclonal-monoclonal antibody sandwich ELISA (PAb-MAb sandwich ELISA) for the detection of Plasmodium vivax antigens were developed. The assays showed good correlation with the level of parasitemia when tested against serially diluted P. vivax parasites (r = 0.937, and 0.997 for MAb-MAb and PAb-MAb sandwich ELISA, respectively), with the ability to detect as few as 6.68 parasites/10(6) erythrocytes and 2.69 parasites/10(3) erythrocytes, respectively. The MAb-MAb sandwich ELISA was specific, since it was positive only with P. vivax-infected erythrocytes from vivax malaria patients and negative when erythrocytes from 34 healthy individuals and 30 falciparum malaria cases were tested. In contrast, cross-reaction was found in the PAb-MAb sandwich ELISA when the plates were coated with polyclonal IgG and tested against the serially diluted P. falciparum SO strain antigen prepared from in vitro cultures. Comparison between the two systems of two-site sandwich ELISA showed that the MAb-MAb sandwich ELISA was superior to the PAb-MAb sandwich ELISA: (1) it gave a higher sensitivity when tested with serially diluted P. vivax antigen preparations from vivax malaria patients; (2) it gave a higher specificity when tested with the SO strain of P. falciparum from in vitro cultures, (3) it gave a lower absorbance value when tested with erythrocytes from healthy individuals. All 281 cases of vivax malaria already proven by microscopic examination were positive by MAb-MAb sandwich ELISA.(ABSTRACT TRUNCATED AT 250 WORDS)


Antibody detection ELISAS for malaria diagnosis.

Parasite extracts of Plasmodium falciparum and P. chabaudi and three synthetic peptides from the P. falciparum MSA2 merozoite antigen were tested for suitability as antigens in an antibody detection ELISA using sera from malaria patients in Brisbane. The P. chabaudi extract was superior to P. falciparum extract for detecting P. vivax cases, while for P. falciparum cases the two parasite extracts were equivalent. Single peptide antigens were generally less sensitive than parasite extracts; however, peptides G3 and G7 were more sensitive than parasite extracts in detecting first attacks of P. vivax. Examination of isotype specific responses demonstrated that this may be explained by higher IgG responses to these peptides in first than in subsequent P. vivax attacks. Because of the differing antibody specificities in primary and secondary P. falciparum and P. vivax cases, the best sensitivity was achieved by using the combined results of assays with three antigens: P. chabaudi, peptide G3 and peptide G7. The combined sensitivity was 77.1% for P. falciparum and 88.6% for P. vivax acute cases with 91.1% specificity.


Artemether in the treatment of multiple drug resistant falciparum malaria.

Artemether has the potential to be an alternative antimalarial for multiple drug resistant falciparum malaria. However, it has been associated with high recrudescent rates which may be due to incorrect dosage regimens. The dosage regimens are varied from country to contry. We have carried out a comparative study of two dosage regimens, ie 480 mg and 600 mg total dose given over 5 days in uncomplicated and severe falciparum malaria. 167 patients were included in the study, 61 with acute uncomplicated falciparum malaria and 106 with severe malaria. All patients showed a good initial response. The difference in total dose had no effect on the parasite or fever clearance time (PCT or FCT). However, the severity of the disease did have some influence of these times. The PCT and FCT from either regimen of uncomplicated malaria were significantly faster than those of severe malaria (p < 0.005 and = 0.05, respectively). The cure rate seems to have some correlation with the amount of drug given and severity of the disease. The cure rates in uncomplicated malaria were 84 and 92%, respectively, for 480 mg and 600 mg. In severe malaria the cure rates dropped to 65 and 76%, respectively, for 480 and 600 mg. We conclude that artemether can be considered as an alternative antimalarial for multiple drug resistant falciparum malaria. However, the cure rate of severe falciparum malaria in this study is not considered satisfactory in areas with multiple drug resistant falciparum malaria. Further studies are needed to assess the curative efficacy with different dosage regimens.(ABSTRACT TRUNCATED AT 250 WORDS)


Preliminary report: a comparative clinical trial of artemether and quinine in severe falciparum malaria.

Twenty-six patients with severe falciparum malaria were randomized to be treated with quinine or artemether. Twelve patients received quinine at the standard dose and fourteen patients received artemether intramuscularly at a total dose of 640 mg over 7 days. The patients were kept in the hospital for at least 7 days. Peripheral smear was performed 6-hourly until there was no parasitemia, then daily until discharged. Adverse effects were monitored through physical examination, laboratory findings and questionnaires. Laboratory examination was performed on admission, day 2, day 4 weekly until discharged. The patients in both groups were comparable in age, body weight, admission parasitemia, hemoglobin and white blood cell count. The survival rates were 93% and 58% in artemether and quinine groups, respectively (p = 0.052 at 95% confidence, using Fisher's exact test). The parasite and fever clearance times, and the time taken to gain consciousness in cerebral malaria patients were not significantly different between the two groups. Adverse effects in the quinine group consisted of dizziness and vertigo which were found in 4 patients. No adverse effects were noticed in the artemether group. This preliminary report suggests that artemether is a good alternative drug for severe falciparum malaria and seems to be better than quinine regarding survival rate and side effects. Confirmation of these findings in a larger study size is needed.


Pharmacokinetics of quinine, quinidine and Cinchonine when given as combination.

Pharmacokinetics of quinine, quinidine and cinchonine when given as a combination were evaluated in Thai patients with falciparum malaria during acute infection and convalescence. The combination of quinine, quinidine and cinchonine was randomly given to thirteen patients at 400 mg or 600 mg (consisting of one-third of each component; 7 patients were enrolled in 400 mg regimen and 6 in 600 mg regimen) intravenously every 8 hours for 7 days. The drug combination was given again at day 35 to define the pharmacokinetics of each drug during convalescence. All patients with the 600 mg regimen had good response with 100% cure rate while patients with the 400 mg regimen had a good initial response but one patient recrudesed on day 46. This particular patient had plasma concentrations of all three drugs lower than the mean values of patients with sensitive responses. The plasma levels of quinine and quinidine obtained from the present study were higher than that expected from one-third of the conventional dose (600 mg) when given alone, suggesting drug combination interaction. The terminal half-lives of each of the three components were prolonged during acute malaria when compared to those obtained during convalescence.


Fansimef for prophylaxis of malaria: a double-blind randomized placebo controlled trial.

At a time when Fansimef, the fixed combination of mefloquine, sulfadoxine and pyrimethamine was considered for prophylaxis of falciparum malaria, a randomized double-blind study comparing the efficacy and tolerability of Fansimef with that of Lariam (mefloquine), Fansidar, chloroquine and placebo in malaria prophylaxis was performed in Thailand from July 1987 to January 1988. The study population of 602 adult males was recruited in Pak Tongchai District, some 360 km North-East of Bangkok, where multiresistant P. falciparum is endemic. All active treatments and placebo were given once weekly for 24 weeks with doses as follows: Fansimef: 125 mg mefloquine + 250 mg sulfadoxine + 12.5 mg pyrimethamine (1 half-strength tablet); Lariam: 125 mg mefloquine (1 half-strength tablet); Fansidar: 500 mg sulfadoxine + 25 mg pyrimethamine; chloroquine; 300 mg. A loading dose of 2 half-strength tablets was given in the Fansimef group in weeks 1 and 2 and in the Lariam group in weeks 1 to 4. The incidence of acute episodes of P. falciparum per 100 person months of prophylaxis was 0.17 each in the Fansimef and the Lariam groups, 1.18 in the Fansidar group, 0.69 in the chloroquine group and 0.64 in the placebo group (differences statistically not significant). Clinically adverse events were reported by 170 subjects (Fansimef 28, Lariam 29, Fansidar 41, choroquine 43, placebo 29; differences statistically not significant). The most frequent adverse events in all groups were headache, sleepiness, dizziness and weakness.(ABSTRACT TRUNCATED AT 250 WORDS)


Malaria in a rural area of eastern Thailand: baseline epidemiological studies at Bo Thong.

Malaria is still a serious health problem in Thailand. Present attempts at controlling the disease by drug treatment and other means remain unsatisfactory. Thus, development of vaccination against malaria is a major research goal of malaria immunology. The objective of this study was to acquire epidemiological base line data for subsequent vaccine trials. A cross-sectional descriptive survey was conducted among 253 local inhabitants during the beginning of the transmission season in July 1989 at Bo Thong District, Chonburi Province, Eastern Thailand where malaria transmission was likely to be moderately high. Following the cross-sectional survey weekly morbidity surveillance was started to detect new cases of malaria by using active and passive case detection at the district hospital, local health centers and at neighboring malaria clinics. Fifty-four percent of the population were male and forty-six percent female: nearly a half (48.3%) were under the age of 15 and 17% under the age of 5 years. Eighty percent of the adults were married. Seventy percent of the subjects interviewed gave a history of malarial illness in the past. Malaria, malnutrition, anemia abnormal hemoglobin diseases and parasitic infestations were the main health problems in the study area. The annual parasite incidence of malaria was 169.4/1,000 population and 77% of parasitemic individuals were asymptomatic, indicating the existence of a semi-immune condition among these subjects. Antibody level to crude parasite antigen increased with age. It is hoped that the information obtained from these field studies may be useful in malaria vaccine trials in the near future.


Dyspepsia in acute falciparum malaria: a clinico-pathological correlation.

Gastrointestinal symptoms are common in acute falciparum malaria. Dyspepsia often occurs in such patients and sometimes it is exceptionally severe. However, the pathogenesis of the dyspeptic symptoms in malaria has not been clearly defined. Upper gastrointestinal endoscopy was performed in 40 patients with acute falciparum malaria in order to correlate the dyspeptic symptoms with the macroscopic (endoscopic) and microscopic (histologic) pathology of stomach and duodenum. The patients were divided into a dyspeptic group (n = 20, male/female ratio = 17/3, age range 18-50 years, mean age = 28.85 + 9.14 years), and a non-dyspeptic group (n = 20, male/female ratio = 16/4, age range 15-47, mean age 26.05 + 9.98 years). The findings revealed that dyspepsia correlated with topographic endoscopic pangastritis (p = 0.0014), the category of endoscopic antral gastritis (p = 0.013), and the histologic severity of antral gastritis (p = 0.0434). The results suggested that gastritis should be considered in acute falciparum malaria patients presenting with dyspepsia.


Eosinophilic response to falciparum malaria infections.

Eosinophilia was a frequently detected incidental finding during a prospective study of malaria seroepidemiology in Thailand. Blood eosinophil counts were performed every 3 months for a year in 823 Thai soldiers on border guard duty in a malaria endemic area. Soldiers developing malaria were admitted to hospital and more frequent eosinophil counts were done. P. falciparum parasitemia suppressed preexisting eosinophilia but eosinophilia returned following treatment. P. vivax and mixed infections had a similar but less marked effect on the peripheral blood eosinophil count. Eosinophilia in persons from a malaria endemic area may represent a normal late response to malaria infection.


Incrimination of Anopheles aconitus Donitz as a vector of epidemic malaria in Bangladesh.

In 1989-91, post-monsoon epidemics of vivax malaria occurred in the central flood plain near Dhaka. Anopheles philippinensis, the usual vector in the paddy field habitat, was not present, but 1.4% of parous An. aconitus were infective. This is only the second time An. aconitus has been incriminated as a vector in Bangladesh. We speculate that the surprising increase in lowland malaria may have been caused by environmental change that favored the survival of An. aconitus.


Studies of hospital social stays in the frail elderly and their relationship to the intensity of social work intervention.

The elderly frequently suffer long lengths of hospital stay (LOS). These long stays are often associated with long social care stays which occur when patients no longer require acute care and are awaiting post-discharge services. In this study, actual acute care LOS and social care LOS were studied specifically in hospitalized frail elderly. Our data demonstrate that frail elderly receiving only acute care do not suffer markedly prolonged total LOS (TLOS). However, in hospitalized frail elderly patients who experience acute care and social care stays, social care LOS accounts for over half of all hospital days. When patients were grouped and studied according to the type of post-discharge services being sought by the health care team, significant differences in acute LOS and social care LOS were noted. Subgroups of patients were also identified among the various groups which differed significantly in their LOS parameters. Patients who required more than one discharge plan during the course of hospitalization experienced the longest hospital stays of all groups, and spent almost 70% of these days receiving non-acute social care. In a study of the relationship between the intensity of social work intervention and social care LOS in the frail elderly, a statistically significant relationship was noted between the timing and frequency of social work intervention and the actual length of social care stays. Early and frequent social work interventions were associated with significantly shorter social care LOS. We conclude that the study of TLOS should include acute LOS and social care LOS to obtain a reliable measure of the course and cost of hospital care for the frail elderly. The study of social care subgroups may facilitate future investigations to define the social care problems which contribute most to TLOS, and the patient populations which should be most heavily targeted for early and intensive social work intervention.


A frame for defining social work in a hospital setting.

A frame for articulating the unique role of social work in a hospital setting is presented which links the patient's experience of the disruptive impact of illness and hospitalization with the historical roots of the profession of social work. The presentation emphasizes the social worker's role in orienting patients and families to the importance of their part in the process of healing and helps partialize this task into specific areas of work with the social worker. A consideration of the process of discharge planning within this framework is discussed.


Social work with multi-family groups: a partnership model for long term care settings.

Residents in long term care facilities suffer from physical and cognitive impairments. As their conditions deteriorate, it is often difficult for families to maintain significant ties with them. Social work can help family members develop meaningful roles in the institution via multi-family groups, an approach which enhances the contributions families can make at a time when family ties and roles need to be redefined. The program has been replicated on all floors in one facility and can be adapted to other settings.


Critical incident stress: the role of hospital-based social work in developing a statewide intervention system for first-responders delivering emergency services.

Emotional, cognitive and behavioral stress can negatively affect the performance of fire, rescue and law enforcement personnel responding to emergency situations. Impaired professional performance in these crises not only endangers the incident victims, all involved responders and their families, but potentially the lives and property of entire communities. This article describes the major administrative and clinical leadership of a hospital-based Social Work department in implementing one of the few statewide critical incident stress debriefing teams for emergency service personnel in the United States. It represents a model for program development by other organizations.


Helping Holocaust survivors with the impact of illness and hospitalization: social work role.

Illness and hospitalization can trigger intense reactions for Holocaust survivors and their families which derive from the brutal and dehumanizing experiences they endured during World War II. Some characteristic problems and reactions to illness and hospital care they and their families experience are reviewed, as are indicated social work interventions based on crisis theory.


The role of computerized information systems in quality assurance in hospital social work departments.

Computerized information systems can be valuable tools in the total quality assurance program of hospital social work departments. This paper presents a matrix of potential roles for the information system at various levels of assessment-structural, process, and outcome. It then illustrates these roles, based on examples from a country-wide information system developed for hospital social work departments in Israel.


Discriminators of willingness to consider cadaveric kidney donation among black Americans.

Black Americans were classified as either willing or unwilling to consider serving as kidney donors according to a combination of demographic and social psychological variables. Findings indicated that, in addition to selected religious variables, willingness to consider donation was associated with gender, age, source of information about organ donation, perceived need for transplants among blacks, self-acceptance of transplant organs and perception of bias in the selection of transplant recipients. Implications of the findings for social work practice and future research are discussed.


Herniation of calcified cervical intervertebral disk in children.

Childhood intervertebral disk calcification is a rare clinical entity and usually has a benign course, generally undergoing spontaneous resolution. However, rapid neurologic deterioration due to herniation, found in both of our cases of calcified cervical intervertebral disks, required urgent anterior discectomy and fusion, resulting in excellent recovery.


Predictors of mortality in severely head-injured patients with civilian gunshot wounds: a report from the NIH Traumatic Coma Data Bank.

Predictors of outcome were examined in this prospective study of 151 patients severely injured by civilian gunshot wounds. Of the 151 patients, 133 (88%) died. Of the 123 patients with an initial Glasgow Coma Scale score of 3-5, 116 (94%) died, whereas of the 20 with an initial Glasgow Coma Scale score of 6-8, 14 (70%) died. There were no good outcomes, and only three moderate recoveries in patients who had initial scores of 8 or less. In those patients who survived long enough for intracranial pressure monitoring, intracranial hypertension predicted a very poor outcome. Computed tomographic scan characteristics such as midline shift, compression or obliteration of the mesencephalic cisterns, the presence of subarachnoid blood, intraventricular hemorrhage, and the presence of hyperdense or mixed-density lesions greater than 15 mL, either bilateral or unilateral, were all associated with a poor outcome. However, neither the caliber of gun nor the distance of the gun from the head significantly affected the risk of dying.


Temporal lobectomy for complex partial seizures that began in childhood.

Forty-six consecutive patients who underwent surgery for intractable temporal lobe seizures originating in childhood are reported; invasive preoperative monitoring (e.g., depth electrodes and subdural arrays) was not used in the selection process. Our results, with respect to the control of seizures and improvement in behavior, are comparable to those of series in which invasive monitoring was used in the selection process. Eighty-five percent of the 46 patients (96% of the 28 operated after the introduction of long-term electroencephalographic monitoring) became either seizure free or experienced near total control of their seizures. Our results indicate that many patients can be selected successfully for temporal resection without exposure to the risk and expense of invasive presurgical procedures. A long duration of epilepsy prior to surgery in patients with neoplasia portended a less satisfactory outcome. Our results strengthen the argument for early operation in children with intractable epilepsy.


Transcranial Doppler waveform differences in hyperemic and nonhyperemic patients after severe head injury.

Although increased cerebral blood flow velocity is readily measured by transcranial doppler ultrasonography (TCD), the causes of the velocity elevation may differ. After severe head injury, increased blood flow velocity can develop both in patients with global hyperemia (suggestive of vasodilation) and in those without hyperemia (suggestive of vasospasm). The present study attempts to determine whether TCD can differentiate these two mechanisms of velocity increase. Fourteen severely brain-injured patients who developed increased middle cerebral artery blood flow velocity (time-averaged mean velocity > 100 cm/s) were studied. Eight cases were nonhyperemic and six were hyperemic as defined by arterial-jugular venous oxygen content differences of more than 4 mL/dL and less than 4 mL/dL, respectively. The TCD waveform of all eight nonhyperemic cases showed a diastolic notch, which was absent in all six hyperemic patients (p = 0.00066). TCD waveform profile appears to provide a noninvasive means of differentiating at the bedside the two causes of increased flow velocity. If associated with raised intracranial pressure, these require different treatment.


Massive bifrontal epidermoid tumor.

There have been 27 cases of epidermoid tumor reported to arise from the frontal or ethmoid sinus area. We report the case of a virtually asymptomatic massive bifrontal epidermoid tumor arising from the ethmoid sinus in a 76-year-old male.


Clinical and neuroradiological correlations in a patient with a wandering retained air gun pellet in the brain.

The authors present the case of a patient with an air gun pellet that moved from the ventricular system into the subarachnoid space of C2-C3, from where it was successfully removed by interlaminotomy.


Postoperative central conduction time and cerebral blood flow in patients with aneurysmal subarachnoid hemorrhage: relationship with prognosis and ischemic conditions.

Cerebral blood flow (CBF) and somatosensory evoked potential (SEP) were monitored periodically on 32 patients who underwent aneurysm clipping within 3 days after subarachnoid hemorrhage (SAH). From the SEP data, central conduction time (CCT) was obtained, and CCT fluctuations were categorized into three types. Patients with CCT prolongation over 7.5 ms within 10 days after SAH tended to have poor recovery of CBF and unfavorable outcome. Therefore, periodical monitoring of CCT was considered as a useful indicator for predicting prognosis and post-SAH changes of cerebral blood flow.


The history of neurosurgical procedures for the relief of pain.

Pain has been a major medical problem from the beginning of recorded history. Since the earliest medical writings, there have been innumerable procedures designed to relieve pain and its suffering. In this study, we have reviewed both the early medical writings of various civilizations and the first modern publications, to compile a history of neurosurgical procedures for the relief of pain.


Dorcas Hager Padget: artist and embryologist.

Dorcas Hager Padget (1906-1973), a largely self-taught illustrator, became a more polished artist under Max Brödel at Johns Hopkins Hospital, before going to work for neurosurgeon Walter Dandy. In search of more information on vascular anatomy, she became an expert neuroembryologist, first in the development of arteries and veins and later chiefly involved with anomalies of neural tube development. She was able to clarify the development of the Arnold-Chiari and Dandy-Walker syndromes.


[Preventive effect of domestic, synthetic beta-carotene on the development of rat mammary tumors induced by DMBA].

Preventive effects of artificial beta-carotene on the development of rat mammary gland adenocarcinomas induced by DMBA were studied in rats maintained on a diet containing beta-carotene at a dose of 2.5 mg per animal within 10 weeks, which was initiated after the carcinogen administration. The carotenoid treatment course caused the following effects: manifestation of adenocarcinomas induced by DMBA was decreased, latent period of neoplasm development as well as the rate of tumor differentiation were increased and metastatic spreading into the regional lymph nodes was inhibited.


[Inhibiting effect of domestic, synthetic beta-carotene and ascorbic acid on endogenous carcinogenesis in mice].

Carcinogenesis in mice induced by the tryptophane derivative 3-hydroxyanthranilic acid was studied after administration of synthetic beta-carotene and ascorbic acid. The incidence of induced hemoblastoses and hepatomas was decreased 2-fold, while the latent period of their development was, increased in mice on a lifetime feed containing 15 mg/kg of beta-carotene. The anticarcinogenic effect of ascorbic acid added to drinking water was similar to that of beta-carotene. The additive inhibitory influence of beta-carotene and ascorbic acid on endogenous blastomogenesis was not found in mice.


[The effect of carotenoids on rat stomach carcinogenesis, induced by N-methyl-N'-nitro-N-nitrosoguanidine].

The effect of natural carotenoids on gastric carcinogenesis induced by N-methyl-N'-nitro-N-nitroguanidine (MNNG) was studied in 4 groups containing 105 rats. Highly carotenoid complex from wild rose fruits was added to drinking water of Group 1 (30 rats) at a dose of 15 mg/kg (as calculated per beta-carotene) 3 times weekly; as well as MNNG was present in water (0.01%). The carotenoid complex was supplemented to the ration 2 months before MNNG treatment and was continued within 15 months; MNNG treatment occurred within 6 months. Group 2 (30 rats) and Group 3 (30 rats) were treated with MNNG and the carotinoid complex, respectively; the 4 group (15 rats) was used as an intact control. Tumors were detected in 16 rats of 28 animals studied in Group 1 (57.1%) and in 11 rats of 25 animals in Group 2 (44%) (P < 0.05); malignization was found in the stomach and small intestine. The rate of involvement with gastric tumor in Group 1 was 3-fold higher as compared with those in the only MNNG treated animals--50% and 16%, respectively (P < 0.01). Tumors of the small intestine were detected in 5 rats of Group 1 (17.8%) and in 9 rats of Group 2 (36.6%); differences were statistically insignificant. However, carcinogenesis tended to accelerate. The mean time of stomach and small intestine tumor detection in Group 1 was equal to 286 and 276 +/- 46 days, respectively, and in Group 2--339.7 +/- 25.4 and 350.7 +/- 25.4 days, respectively (differences are insignificant.(ABSTRACT TRUNCATED AT 250 WORDS)


[The effect of lipochromin on spontaneous carcinogenesis in mice].

Development of spontaneous hepatomas was studied in CBA mice, which were maintained on a diet containing the carotenoid drug lipochromine in a dose of 25 mg/kg during their life beginning at the age of 3 months twice a week. Concentrations of vitamin A (as retinol) and beta-carotene were estimated in mice blood and liver tissue by means of HPLC. Decrease in occurrence of spontaneous tumors in liver tissue as well as distinct increase in periods of their development were detected in the animals treated with the drug. The phenomenon observed correlated positively with an increase in concentration of beta-carotene in liver tissue of tumor-bearing mice, thus indicating the preventive effect of lipochromine on spontaneous carcinogenesis in mice CBA strain.


[The modified effect of carotenoids on rat forestomach carcinogenesis, induced by N-methyl-N'-nitro-N-nitrosoguanidine].

A modifying effect of carotenoids on carcinogenesis induced by N-methyl-H'-nitro-N-nitrosoguanidine (MNNG) in the rumen was studied in four groups of rats weighing 100-120 g. A diet of the first group contained a highly carotenoid complex from wild rose fruits at a dose of 30 mg/kg 3 times weekly; MNNG was administered at a dose of 5 mg per animal by means of a gastric tube for two days. Administration of the drug was repeated within 5 days. Treatment with the carotenoid complex was carried out 2 months before the MNNG administration. Group 2 and 3 received only MNNG or the carotenoid complex, respectively; Group 4 served as intact control. Tumors were detected in 33 rats of 81 animals studied (40.7%) in Group 1 and in 53 rats of 74 animals (71.6%) of Group 2 (P < 0.01). The mean time of the tumors detection constituted 40.7 +/- 9.5 days in Group I and 68.7 +/- 0.3 days (P < 0.05) in Group 2. All the tumors detected were localized in the rumen and consisted of papillomas appeared mainly as multiple forms. The data obtained suggest that carotenoids exhibited the modifying effect on MNNG-induced carcinogenesis of the rat rumen.


[Antimutagenic properties of substances containing beta-carotene].

Two carotene-containing drugs (natural and artificial) were shown to decrease the rate of chromosomal aberrations, induced by cyclophosphane, in bone marrow cells of mice, daily ration of which contained 10-20 mg/kg of beta-carotene within 1-3 weeks. The rate of chromosomal aberrations induced was decreased 1.5-2-fold in various experiments. Artificial beta-carotene exhibited aftereffect within at least 3 days, while its protective effect was decreased about by 20% within 7 days after administration.


[Immunopharmacokinetics of synthetic beta-carotene].

The immunopharmacology and pharmacokinetics of synthetic beta-carotene were studied in complex clinico-laboratory investigations after single and repeated per os administrations of various doses of the drug to healthy volunteers and cancer patients. Repeated treatment with beta-carotene at a dose of 30 mg caused no significant changes in the immunological parameters studied. However, treatment with a dose of 250 mg altered the parameters as follows: alteration of beta-carotene content in blood, elevation of the counts of lymphocytes and T lymphocytes forming "active" rosettes, increase in the proliferative response of lymphocytes to the mitogen PWM and activation of natural killers. Single administration of the drug in a dose of 1,000 and 2,000 mg led to short-term reversible immunodepression, appeared as leukopenia, abolition of the proliferative response of lymphocytes to mitogens and inhibition of T suppressors. Kinetics of retinoids and beta-carotene content in blood plasma was studied after single per os administration of drug megadoses.


[The effect of beta-carotene on interleukin-2 production and mitogen-induced proliferation of T-lymphocytes].

Interleukin-2 (IL-2) production followed by with aftereffect of the immunosuppressive agent hydrocortisone and mitogen-induced proliferation of T lymphocytes were studied in the presence of artificial beta-carotene. Treatment of CBA mice with the drug was performed within various periods. beta-Carotene was found to elevate IL-2 secretion and the effect was both time- and dose-dependent. The drug removed immunosuppression developed after intraperitoneal administration of hydrocortisone. At the same time, beta-carotene stimulated mitogen-induced proliferation of T cells, which was dose-dependent.


[Correction of primary and secondary immunodeficiency with synthetic beta-carotene].

Immunotropic activity of artificial beta-carotene was studied in primary immune response to thymus-dependent antigen (sheep erythrocytes) using models of primary (inherent) and acquired (vinblastine-induced) immunodeficiency. The experiments were carried out using two strains of CBA and C57Black mice with dissimilar responses to the antigen. beta-Carotene was found to remove both acquired and inherent immunodeficiency. The immunostimulating effect of the drug studied appears to be related to the activated production of mediators, namely IL-2.


[The effect of beta-carotene on the dynamics of ornithine decarboxylase activity in atrophic mucous membranes and in stomach polyp tissue].

Activity of ornithine decarboxylase was significantly increased, reaching the maximal values in malignant gastric tissues, in mucosal membrane and polypous tissue of patients with atrophic gastritis as compared with normalcy. Any alterations in the enzymatic activity were not observed in the gastric mucosal membrane of 19 patients with atrophic gastritis within 3 weeks. At the same time, statistically significant decrease of the abnormal high activity of ornithine decarboxylase was detected in atrophic gastric mucosal membrane of 12 patients among 20 patients examined, which were treated with 20 mg of beta-carotene daily within 3 weeks; the enzyme activity was decreased also in polypous tissue of 5 patients in the group of 9 patients studied. Decrease in the ornithine decarboxylase activity after beta-carotene treatment involved improvement of the mucosal membrane state, where hemorrhage disappeared and inflammation reduced. Since the high activity of ornithine decarboxylase is related to promotion of cancerogenesis, beta-carotene appears to exhibit an anticarcinogenic effect as it decreases the enzymatic activity in gastric mucosal membrane.


[Potential cancer-protective effect of beta-carotene in experimental stomach carcinogenesis].

Effect of beta-carotene on content of some metabolites of lipid peroxidation and activity of ornithine decarboxylase was studied in rat gastric mucosal membrane during gastric carcinogenesis developed after administration of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). Intragastric administration of MNNG led to a significant increase in content of diene ketones and malonic dialdehyde in the gastric mucosal membrane within a day, while beta-carotene normalized or decreased considerably the MNNG produced accumulation of these lipid peroxidation products. In acute experiments with MNNG beta-carotene administered per os at a dose of 0.5 mg per animal did not affect the pronounced activation of ornithine decarboxylase in the gastric mucosal membrane. However, in chronic experiments with MNNG repeated administration of beta-carotene led to statistically significant decrease of the constitution-dependent enzymatic activation in the gastric mucosal membrane and to inhibition of locus formation with abnormally high activity of ornithine decarboxylase. The findings suggest that anticarcinogenic effect of the natural antioxidant beta-carotene was shown at the step of carcinogenesis promotion.


[Modification of the body's resistance to acute ionizing radiation by synthetic beta-carotene].

Radiomodifying efficiency of short-term and chronic medicinal and treatment-prophylactic enrichment of rations with artificial beta-carotene, administered at single doses of 0.1-10.0 mg, were studied after acute external gamma-irradiation of adult nonlinear and Wistar rats (0.029 Gy/s) or female SBA mice (0.0037 Gy/s), where the absorbed dose was equal to 8-3 Gy or 9.9-9.5 Gy, respectively. Suspension of beta-carotene paste in olive oil accelerated death of rats irradiated at doses of 8 and 7 Gy (P = 0.04), and shortened their lifespan. At a dose of 6 Gy single and long-term enrichment of rations with beta-carotene decreased the rate of rat death within 30 days from 33.3% to 16.7% (P = 0.14) and 3.3% (P = 0.01), while their life time was increased from 48 days to 67 days (P = 0.05) and 508 days (P = 0.01). beta-Carotene was found to affect favourably the radiation-induced (5 Gy) leukocytopenia, and decreased thymus mass (6 Gy) and body weight (8 Gy). In treatment-prophylactic enrichment with beta-carotene of mice (9.9 Gy) ration their survival was increased from 15% to 30% and lifespan from 14.4 days to 28.9 days (P = 0.05). During medicinal or treatment-prophylactic courses of beta-carotene death of mice (9.7 Gy) was decreased from 75% to 35% (P = 0.01) or 60% and life time was increased from 16.7 days to 22.17 days or 39.9 days (P = 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)


[Certain parameters of beta-carotene metabolism in the rat].

Concentration of retinoids was decreased from 24.5 micrograms/100 ml to 13.5 micrograms/100 ml of blood serum in rats with ageing, during 2-11 months; these rats were maintained on a standard ration. Enrichment of rat ration with beta-carotene caused a statistically significant increase in content of retinoids in blood serum from 24.5 micrograms/100 ml to 48.6 micrograms/100 ml within early periods (1-72 hrs), while within later periods (0.25-2 months) the retinoid content was similar to that of control intact animals. After single and, especially, in long-term treatments with beta-carotene dose-dependent deposition of the carotenoid and increase in content of retinoids were detected in liver tissue. Use of white rats is of importance in principle for evaluation of beta-carotene caused modifications of pathological states developed under influence of unsuitable environmental factors.


[The effect of administration of beta-carotene in an oil solution on its blood serum level and antioxidant status of patients with duodenal ulcer and erosive gastritis].

Adequately good consumption of beta-carotene was observed in patients with duodenal ulcer and erosive gastritis after daily treatment with 18 mg of the carotinoid used as 0.1% oil solution: concentration of beta-carotene was increased approximately 3-fold in blood serum of these patients. Concentration of retinol was not increased in blood serum after treatment with beta-carotene, thus indicating that the drug treatment was not dangerous. Treatment with beta-carotene led to improvement in the state of the antioxidative system of these patients as resistance of erythrocytes to peroxide hydrolysis was increased while content of malonic dialdehyde was decreased in blood serum. The carotene treatment contributed to arresting pain syndrome in patients with ulcers, to cicatrization of ulcers and to disappearance of gastric mucosal membrane erosion.


[Distribution of beta-carotene in the rat upon its intraperitoneal administration in water soluble and oil forms].

Accumulation and excretion of beta-carotene in rat liver tissue were studied when the carotinoid was intraperitoneally administered as olive oil as suspension and a water liposomal suspension. Single injection of the liposomal form of beta-carotene caused an increase in its content in liver tissue. If beta-carotene was administered at a dose of 10 mg/kg its maximal content 44 mg/g of the tissue was observed within one day, and at a dose of 50 mg/kg, its maximal content constituted 178 mg/g within two days. Administration of beta-carotene as an oil suspension at a dose of 50 mg/kg led to a considerably slight accumulation in rat liver tissue with the maximal value of 12 mg/kg of the tissue within two days. Possible use of beta-carotene various forms, as well as experimental models for study their biological activity are discussed.


[The effect of nitrogen-containing derivatives of 1,4-naphthoquinone on mitochondrial lipid peroxidation].

Nitrogen-containing derivatives of 1,4-naphthoquinone synthesized in the form of donor-acceptor autocomplexes, may serve as highly effective antioxidative agents exhibiting their properties both in microheterogeneous medium (water-micellar Tween 80 solution) and in enzymatic and nonenzymatic oxidation of lipids in mitochondria. Some of these complexes studied, where intramolecular transfer of a charge occurred during nonenzymatic oxidation in mitochondria, were only slightly less effective in the antioxidant activity as compared with the standard antioxidant ionol. Distinct increase in the antioxidant activity of the most substances studied was detected in presence of reductases participating in mitochondrial chains of electron transfer and two of these drugs proved to be more effective as compared with menadione and ionol. The data obtained are of importance for pharmacological prognosis of these new biologically active substances efficiency.


[Development of substances for active prevention of cancer based on vitamins and preventive-treatment products].

The conception and program are described for development of drugs involved in active prophylaxis of malignant neoplasms. Development of prophylactic drugs and new treatment-prophylactic food-stuffs was shown to be possible and expedient to use toxic immunomodulators and natural anticarcinogens. Complex drugs are assumed to include carotenoids, tocopherols, water-soluble vitamins, polysaccharides and other biologically active substances exhibiting anticarcinogenic, antimutagenic and immunostimulating properties. New treatment-prophylactic food-stuffs are developed using milk protein concentrates, lyophylized cruciferous and vegetable juices and extracts of medicinal herbs. The work is realized in the research association involving academic, branch and educational institutions according to State priority programs.


[Xenobiotic-metabolizing enzymes in rat liver and small intestinal mucosa with varying combinations of polyunsaturated omega-6 and omega-3 fatty acids in the diet].

Male Wistar rats were fed for 30 days semi-synthetic diets containing lard, corn oil or fish oil (ichthynic oil from herring muscles), differing in total content of saturated and polyunsaturated fatty acids (PUFA), in the ratio omega 6/omega 3 PUFA and in content of vitamin E. The activity of xenobiotic metabolizing enzymes was similar in liver of rats fed diets with lard or corn oil, while activities of epoxide hydrolase and UDP-glucuronosyltransferase were significantly higher if fish oil was used. The type of fat affected also the benzyl-produced induction of the enzymes. Differences in the enzyme activities observed did not depend on content of vitamin E in dietary fats. Unlike liver tissue, activities of microsomal enzymes were not considerably altered in rat small intestine in various experimental groups. The microsomal lipids of liver tissue and small intestine mucosal membrane were similar in the total content of saturated and unsaturated fatty acids in various animal groups but the level of omega 6 and omega 3 PUFA in the tissues depended on the ratio omega 6/omega 3 PUFA in diets.


[Intravascular ultrasound: a new dimension of invasive vascular diagnosis].

Intravascular ultrasound is a new imaging modality which allows the visualization of the vessel wall in vivo and could thus become an important adjunct to conventional angiography. Using miniature high-frequency transducers mounted at the tip of flexible catheters, high-resolution cross-sectional images are created and displayed in real-time. Several investigations have shown good correlations between ultrasound and histologic or angiographic techniques for the measurement of cross-sectional dimensions. Atherosclerotic lesions can be characterized by their differences in echo-density as calcified, fibrous or lipoid. Initial clinical studies have demonstrated the possibility to detect acute changes, such as dissections, following PTCA and other interventions. Several potential clinical applications are being discussed, where intravascular ultrasound may yield valuable information in addition to that provided by angiography. If some important current limitations can be overcome, this method may add a new dimension to invasive vascular diagnostics.


[Transesophageal echocardiography from the surgical viewpoint].

Following the development of new techniques in echocardiography and especially of Doppler color flow imaging, a new dimension of cardiac surgery has been brought about. The use of transesophageal probes facilitates routine surgery to be performed without interferences and, also, comparability between repeated ultrasonic measurements. Originally, echocardiography was mainly applied for quality control by comparing pre- and postoperative echocardiograms. Now it is equally important in perioperative strategy planning guiding the surgeon's decision throughout the operation as well as in cardiac emergencies. Using intraoperative echocardiography routinely in cardiac surgery establishes a more and more close cooperation between surgeons, cardiologists, and anesthesiologists. In order to evaluate the clinical relevance of echo findings, they have to be repeatedly correlated to surgical realities and to long term results of clinical outcome.


[Possible reasons for bilirubin accumulation in the brain of newborn animals during oxygen deficiency].

An increase in content of bilirubin was detected in brain tissue of newborn rats with chronic interrupted hypoxic hypoxia occurred during pre- and neonatal periods. Accumulation of bilidiene in animal brain tissues appears to occur due to the following causative factors: tissue acidosis, developed after oxygen deficiency, contributed to binding of bile pigment to brain cell plasma membranes, synaptosomal ones in particular; serum albumin lost its specific ability to bind bilirubin due to protein molecular accumulation of excessive fatty acids and acetaldehyde, which are bound to protein, as well as other minor ligands extracted by organic solvents.


[Medical-biological aspects of carotenoids].

The literature data involving 45 references are reviewed. Metabolism of carotenoids in human and animal tissues, distribution in tissues, antioxidative and immunomodulating activities of carotenoids, their anticarcinogenic properties are discussed. Use of remedial drugs containing beta-carotene holds much promise.


[Transcranial Doppler ultrasound in intensive care medicine].

Transcranial Doppler sonography (TCD) enables measurement of blood flow velocities in the basal intracerebral vessels. The most important applications of TCD in the ICU are the diagnosis and monitoring of vasospasms caused by subarachnoid hemorrhage after rupture of an aneurysm. Further indications are the non invasive diagnosis of critical decreases of cerebral perfusion pressure, the evaluation of brain death and the monitoring of thrombolysis of occlusions of the middle cerebral artery. TCD lends itself as a valuable non invasive bedside-monitoring tool, which enables continuous or intermittent monitoring of intracerebral hemodynamics without strain for the patients. Disadvantages to be mentioned are the dependence of experienced examiners and the long lasting training phase required to achieve the requisite experience.


[The value of echocardiography in diagnosis of bacterial endocarditis].

In recent years echocardiography has become the most important method for the diagnosis of bacterial endocarditis. Though identification of valve vegetations by M-mode echocardiography was rather limited, two dimensional echocardiography--especially with transoesophageal application--has a sensitivity of more than 90% and a specificity of 98%. In addition, echocardiography is able to supply valuable contributions for the evaluation of the patient's prognosis and in the identification of complications of infective endocarditis, such as: the extent of valve destruction, rupture of chordeae and other parts of the valves, as well as the presence of intramyocardial and paravalvular abscesses. In addition, the application of Doppler-echocardiography allows the semiquantitative evaluation of the degree of any valve insufficiency.


[Nisoldipine in comparison with long-term nitrates].

Nisoldipine represents a new attractive second generation calcium channel blocker of the dihydropyridine-class for the treatment of all types of coronary artery disease. The effect on chronic ischemia is comparable to long-acting nitrates, side-effects have been rarely observed. The advantages will be the high vascular selectivity with only slight negative inotropic effect as well as a long-lasting positive influence on the myocardial metabolism. Up to now, no studies have been reported which compare nisoldipine and long-acting nitrates directly, but this calcium antagonist appears to influence duration and intensity of symptomatic and silent episodes of ischemia similar to the nitrates.


Efficacy, safety and tolerability of lovastatin and bezafibrate retard in patients with hypercholesterolemia.

Hyperlipidemia has turned out to be the most important risk factor for coronary heart disease and necessitates frequently lipid lowering long-term treatment. Therefore, efficacy and tolerability of hypolipemic drugs are of great interest. The objective of the present study was to compare the safety, tolerability and effect on plasma lipids of Lovastatin and Bezafibrate retard in patients with hypercholesterolemia. 99 patients with total cholesterol of > or = 250 mg/dl after a 4 week standard lipid-lowering diet were treated another 4 weeks with placebo and then randomized to 400 mg Bezafibrate retard or 20 to 80 mg Lovastatin given once a day for 12 weeks. Mean changes from baseline in total cholesterol, LDL cholesterol and triglycerides were significantly reduced, in HDL cholesterol increased in both treatment-groups (p < or = 0.01). The effects of Lovastatin on total cholesterol and LDL cholesterol were more pronounced than those of Bezafibrate retard (p < or = 0.01), while Bezafibrate had a larger effect on triglycerides (p < or = 0.05). The frequency of clinical adverse experiences was low and similar among treatment groups, the frequency of laboratory adverse experiences was higher in the Lovastatin group. One patient in the Bezafibrate group was withdrawn because of nausea, one patient in the Lovastatin group because of GGT elevation.


[Schmidt syndrome--a case report].

Pathologic organ specific autoimmune disease frequently affect endocrine glands and mostly lead to an insufficiency of the organs involved. Immunoendocrine diseases often occur in a polyglandular fashion and are consequently termed autoimmune polyglandular syndromes or immunoendocrinopathy syndromes. Among the different types one of the most frequent is known as Schmidt's syndrome or typus tyreosuprarenalis. Two case reports typical for this syndrome are described from a clinical point of view indicating also the respective diagnostics.


[Vocal physiopathology].

Cordectomies usually result in alteration of the glottic sphincter which in turn effects the activity of the entire larynx bringing about different types of dysphonia according to the resulting scarring pattern in the glottic floor and to the functional recompensation made by the cordectomized patients themselves. Today, study of those anatomic dynamics which determine voice typology in cordectomized patients is possible thanks to various means: synthesis of data obtained from psycho-perspective analyses of the vocal product, video-fiber-laryngoscopic observation of the vocal tract and spectrographic study. The above-mentioned examinations show how the type of dysphonia in these patients is determined by the various combinations of different scarring patterns, which also depend on the entity of surgical exeresis, and the position taken on by various laryngeal district during phonation? The authors present paradigmatic clinical cases in order to demonstrate the different phonatory capabilities achieved by patients who had undergone either cordectomy or cordectomy extended to the ventricle and false vocal cords.


[The clinical presuppositions and results of logopedic therapy].

Logopedic therapy is proposed in helping cordectomized patients learn to best use pneumo-phonal structures to compensate for the glottic insufficiency often resulting from this type of surgery. Rehabilitation showed be initiated as soon as possible following surgery before the patients starts using compensation mechanisms negative for voice quality. However, precisely those patients often receive therapy tardively when the anatomo-functional results have already been consolidated and the voice quality is poor. The rehabilitation discussed uses classical feed back mechanisms through which the subjects learn to recognise those factors which enable them to better their voice quality. The type of exercises to be employed depends on whether or cordectomy extended to the ventricle and to false vocal cord. On the farmer case, the principle aim of therapy is that of nearing the healthy vocal cord to the neocord through appropriate exercises. On the better case, instead, the main vocal compensation is the result of the perfect coordination of expiratory energy and the activity of the healthy vocal cord. In fact, in extended cordectomized patients, in the light of the modest amount of scarring, it is necessary to cause the healty voice cord to shift entirely towards and beyond the median line as to as compensate for a sphincteric loss. The authors report two clinical case, particularly difficult from a rehabilitation point of view, in which, relatively speaking, in light of the initial voice conditions, satisfactory results were obtained.


[The use of Phonagel in glottic insufficiency].

The authors describe their experience concerning collagen implantation in case of glottic insufficiency after cordectomy by the CO2 Laser. Three different kinds of injection are indicated as follows: injection of 3/4 of collagen in the site responding to vocal fold removal on 1/4 in the survival fold after cordectomy with conservation of the thyroarytenoid muscle; implantation of 1/2 in the new fold and 1/2 in the surviving one after cordectomy with removing of the cricoarytenoid muscle; infiltration of the whole material in the residual vocal fold after cordectomy enlarged to the false vocal fold and the ventricule as well. Video laryngoscopic and spectrographic examinations documented good phonatory results after collagen implantation in 19 cases over 21; two cases had a persisting insufficiency depending on the fact they had been previously operated of enlarged cordectomy and the scar tissue was not sufficient for measures and consistency to obtain a satisfactory injection of collagen.


[Phonatory rehabilitation via esophageal voice and the laryngophone].

Esophageal voice obtained through logopedic treatment and speech produced by electronic prostheses is the principal means of verbal communication of laryngectomized patients. Several factors condition the success of logopedic rehabilitation: entity of hypopharyngeal surgical exeresis and scar repairing modalities; rehabilitation technique employed; patient's skill in controlling pharyngo-esophageal tract and articulation organs; patient motivation. A previous study executed by our School reported that only the 20% of the patients who did not practise logopedic therapy employed the laryngophone. Reduced use of electronic prosthesis depends on three factors: acoustic products of poor quality; evidence of anatomic and functional impairment pointed out by laryngophone use; limitation of manual activity during phonation. Electronic prostheses have a precise indication in the following cases: immediately after surgery; in case of logopedic treatment failure and when tracheo-esophageal prosthesis are contraindicated; when the esophageal voice has an insufficient volume or in noisy environments. Finally indicative criteria to introduce patients to the most suitable rehabilitation modality are reported.


[Tracheoesophageal prostheses].

The AA. report their own experience in the field of tracheoesophageal speech rehabilitation of laryngectomees. In order to get a high rate of successful results, (an accurate selection of patients is of fundamental importance) mainly to identify the physical requirements and the motivational aspects potentially favouring vocal, rehabilitation. The personal technique of tracheoesophageal fistula creation under local anesthesia is illustrated, the procedure generally last 5-10 minutes with minimal tissue trauma and blood loss and is also suitable for outpatients. For the above-mentioned reasons, the AA. prefer to perform the tracheoesophageal puncture as a secondary procedure, i.e., after total laryngectomy, taking into account the many inconveniences related to primary rehabilitation, as reported in literature. Finally, advantages and inconveniences of the various types of prosthetic devices employed are illustrated and the causes of failure are discusses.


[Esophageal voice: a critical analysis of the results obtained by different rehabilitative technics].

In order to evaluate the phonatory results obtained with the use of tracheoesophageal prostheses, 38 laryngectomees were examined, 20 of which underwent erigmophonic voice rehabilitation while the other 18 were rehabilitated with the application of a prosthesis. In all cases electroglottography and spectrography of the voice were performed. In the erigmophonic-voice subjects, electroglottography gave a normal glottic wave while spectrography gave a tracing with frequent interruptions, scarce harmonics, altered by the presence of background noises. In the tracheoesophageal prosthesis patients, the electroglottogram showed regular hypopharynx vibratory activity while the spectrogram appeared free of interruptions activity while the spectrogram appeared free of interruptions and presented a uniform distributions and presented a uniform distribution of suffixes. The data obtained demonstrate that better results are obtained with the use of tracheoesophageal prosthesis as it allows the exhaled air to be used in phonation and thus respects respiratory dynamics and pneumophonic synergism. It also makes it possible to achieve a clear, fluent voice. Furthermore, the results obtained with patients with this prosthesis were constantly satisfactory when the long exercises required were performed.


[The restoration of the vocal possibilities for the laryngectomized patient with a tracheoesophageal prosthesis].

The experience reported concerning vocal rehabilitation employing tracheoesophageal prostheses (TEP) in laryngectomized subjects at the University of Milan is based upon 149 patients who underwent procedures for total laryngectomy from November 1986 on in nearly all cases (137), a primary procedure was followed in order to insert a Blom Singer prosthesis. Some technical modifications in creating the fistula during the reconstruction phase of laryngectomy reduced the number of postoperative and local complications of the fistula. The men phoniatric rehabilitation time is 38 days from the procedure. The most important aspects affecting the length of rehabilitation are the presence of lower respiratory tract disorders and contemporaneous postoperative radiotherapy. The mean lifetime of the prostheses is 92 days, the main restricting factor being the care taken by the patient. Microbiological studies showed the virtually constant association between fungi and Pseudomonas sp. Nevertheless, infection of the fistula and forced removal of the prosthesis occurred only in 1 patient. Other complications were as follows: granulation tissue at the tracheal side of the fistula into the trachea or oesophagus, 6 and 1 respectively; enlargement of the fistula, 5; others, 15. Fifteen percent of the patients does not succeed in achieving a tracheoesophageal voice because of respiratory insufficiency, difficult neuromuscular control or psychological problems.(ABSTRACT TRUNCATED AT 250 WORDS)


[The experience of early rehabilitation].

Functional laryngectomies permit a more or less ideal preservation of laryngeal functions whose recovery, especially in les conservative operations, occurs very slowly and depends on several conditions: post operative course, sensitivity and motility of the hypopharynx, patient's ability to restore swallowing mechanisms. The Authors relate their experience concerning use of a rehabilitative program partially based on the experiences of some French logopedic schools and partially original. They illustrate the steps and goals of this program which starts on the fifth post-operative day with respiration exercises immediately followed by eight days of exercises to re-establish arytenoid mobilization and swallowing movements. If deglutition is not completely recovered and important inhalation problems persist, the logopedic approach is integrated with surgical rehabilitation consisting of one or more injection of gax-collagen. It is possible to use the same surgical technique later, after hospital discharge, if a slight dysphagia is still present in spite of continuous logopedic rehabilitation. Voice restoration exercises are introduced in the last days of the hospital stay when the patient is tube-free and continues at the office or outpatient clinic for two or three times every week. Concerning removal priority (tracheotomy tube followed by nasogastric tube or vice versa), we propose a diversified strategy for each patient, depending on the anatomicofunctional postoperative situation. Up to now 25 patients have taken part in this rehabilitation program (14 cricohyoidopexy, 6 Cricohyoidoepiglottopexy, 5 supraglottic laryngectomies). The results with regard to the amount of time that nasogastric feeding as well as tracheal tube are kept and the length of the hospital stay, were compared to those ones of a similar number of consecutive cases operated at our institution (ENT Department of Modena University) before February 1990 but not rehabilitated. In the early rehabilitated group, we observe a quicker functional recovery with a shorter hospital stay (about a week).


[Functional recovery in subtotal laryngectomies].

Subtotal laryngectomy, a valid treatment for carefully selected patients, is a safe oncologic procedure which preserves the cricoid-arytenoid unit creating a successful "neo-larynx" with valid phonatory and deglutition functions. At the E.N.T. Clinic of "La Sapienza" University of Rome from Jan. 1984 to Feb. 1992, 85 subjects underwent subtotal laryngectomy, 50 of which then underwent phoniatric examination. The remaining patients were not suitable candidates because of the trachealis cannula (14), or because they were lost at follow up (16). A total of 50 male subjects were examined. Twenty-eight underwent crico-hyoid-pexia, while 22 patients underwent crico-hyoid-epiglotto-pexia. Attention is drawn to the results which appear to be extremely variable with regard to each study group. We obtained better results with crico-hyoid-epiglotto-pexia than with crico-hyoid-pexia and we guaranteed a good social re-insertion in all cases.