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[Hepatic coma. Principles of pathogenesis and treatment. 2: Treatment, prognosis].

According to the multifactorial pathogenesis of hepatic coma, generally caused by the increased formation of toxic protein metabolites in the gut, the most important therapeutical measure is the cleaning and acidifying of the gut. This is possible very simply and cheaply by high enemas of sodium acetate buffers of pH 4,5 and lactulose. If necessary, neomycin or paromomycin must be administered in high doses of 6--8 gm/daily to reduce the pathogenic intestinal bacteria. The detoxification capacity of liver and brain can be improved by intravenous and later oral administration of ammonia reducing amino acids such as arginine, ornithine, and aspartic acid (10--20 gm/daily). They diminish also the elevated serum phenols. Very helpful are also branched chain amino acids which improve apparently the detoxification capacity of the muscle. Very important is the normalization of disturbances of the water and electrolyte balance, especially the normalization of hypokalemia. Very difficult is a successful treatment of cerebral edema and the disturbances of blood coagulation. In special cases of endogenous hepatic coma liver perfusions, hemodialysis, charcoal perfusions a.s.o. can eliminate successfully toxic protein metabolites, whilst this treatment is generally insufficient in the more frequent exogenous hepatic coma. In summary the prognosis of hepatic coma is also nowadays very serious and can only be improved by the early recognition and elimination of exacerbating factors.

Combined Modality Therapy↗

Epizootic of balantidiasis in lowland gorillas.

Acute enteritis characterized by watery diarrhea and lethargy occurred in 4 lowland gorillas (Gorilla gorilla gorilla) during a 5-week period at the Los Angeles Zoo. Numerous trophozoites of Balantidium coli were seen in fresh feces from each gorilla. Potentially pathogenic bacteria were isolated from 1 fecal sample. Results of fecal flotation examinations were negative for eggs of metazoan parasites. The gorillas were treated with antibiotics and metronidazole or paromomycin, or both. The most severely affected gorilla had blood and mucus in its feces, became dehydrated, and required hospitalization for supportive fluid therapy. This gorilla as well as the other gorillas recovered rapidly with treatment. Balantidium coli was not seen in fecal samples after the gorillas' recovery.

Animals↗

[Fistulas complicating diverticular disease of the colon].

Five patients were admitted to the 1st and 2nd Division of General Surgery of Soronno Hospital between July '75 and September '78 suffering from fistulas complicating colon diverticulosis. A sixth patient, operated on for diverticulitis, developed a stercoraceous cutaneous fistula in the postoperative period. This was closed by conservative therapy. A woman patient suffering from colo-enteric fistula, was not operated because she refused. In all operated patients, broad resection of the sigmoid was carried out with end-to-end anastomosis. In three cases a caecostomy was formed to protect the anastomosis. All operated patients were treated preoperatively with laxatives, clysters and intestinal antibiotics, prevalently paromomycin and in one case neomycin plus base erythromycin. Surgery led to the cure of all patients treated.

Aged↗

Treatment with letrazuril of refractory cryptosporidial diarrhea complicating AIDS.

Thirty-five AIDS patients (mean CD4 count 44 x 10(6)/L) with chronic cryptosporidiosis were treated with letrazuril at an initial oral daily dose of 50 mg in an open-label Phase I prospective trial. Treatment was continued for > or = 10 days and for as long as there was a response. The majority of subjects (91%), had previously failed paromomycin treatment. At baseline, 74% of patients had moderate (five to nine bowel movements per day) to severe (> 10 bowel movements per day) diarrhea. Twenty-three subjects (66%) had a clinical response within a mean of 1.7 weeks of treatment initiation. Twenty-two patients had a partial response (> 50% reduction in bowel movements per day for > or = 1 week), one patient had a complete response (two or fewer bowel movements per day). Of the responders, 15 (65%) had a clinical relapse with worsening diarrhea at an average of 1.2 months following initiation of letrazuril. The other eight (35%) had had symptom control for an average of 2.9 months from initiation of letrazuril to the latest follow-up. Microbiologic eradication was demonstrated in 10 (40%) of 25 patients with follow-up stool examinations. Seven patients (20%) experienced a rash, all within 1 week of starting the drug, and resolved in all patients when the drug was discontinued. In conclusion, severely immunocompromised AIDS patients with refractory cryptosporidiosis may show a modest, short-lived response to letrazuril. Microbiologic response is variable and relapse high. Rash is a major limiting side effect of the drug.

Acetonitriles↗

The natural history of diverticular disease of the colon: a role for antibiotics in preventing complications? A retrospective study.

Medical and surgical treatment of diverticular disease has to be set against a background of incomplete knowledge of the natural history and geographical differences of the disease, and difficulties in its definition and classification. This clinical retrospective study was performed to answer the following questions: 1) what was the clinical course after an episode of acute diverticulitis, obliging to an hospital admission? 2) what was the role of cyclic course of antibiotics, if any, in reducing the risk of complications? We examined all admissions to the surgical ward from 1967 to 1991 for a complication of diverticular disease: we looked for occlusion, perforation, fistula, or bleeding. Patients not operated with diverticular disease have been divided in 2 groups, that is patients with a medical prescription at the end of hospital period, and patients admitted without a drug prescription. All patients have been prescribed bulk agents. The medical prescription included monthly cycles of 1 week of oral antibiotics (Neomycin associated with Bacitracin, Paromomycin, or 1989 Rifaximin). We looked for the natural history of the disease in the 2 groups (the "drug" group and the "no drug" group) after the first admission, that is the development of new complications of the diverticular disease and the reason for readmissions, calculating the Absolute Risk Reduction (the difference in event rates between the treatment and control groups) and the Relative Risk Reduction (the difference in event rates between the treated and control groups, divided by the event rate in the control groups). The total number of admitted patients in the period 1967-1991 was 505. A statistically significant trend in favour of a risk reduction of new admissions in the group given antibiotics seems evident.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

[Resistance to beta-lactam antibiotics and aminoglycosides in gram negative bacteria. 1. Molecular and genetic characterization of R-factors (author's transl)].

With frequent use of aminoglycoside antimicrobials and beta-lactam antibiotics in hospitals in the last few years, the number of bacterial strains resistant to these chemotherapeutics increased. Lately, strains of E. coli, Klebsiella, Enterobacter, Serratia, Proteus and Pseudomonas resistant to many antimicrobials (ampicillin, carbenicillin, cephalothin, chloramphenicol, gentamycin, tobramycin, sisomycin, neomycin, paromomycin, kanamycin, streptomycin, spectinomycin, tetracycline, sulphonamides) were isolated from patients of the university hospital in Zuerich. The resistant phenotype of two representative strains (Klebsiella pneumoniae 1 and Serratia marcescens 2) could be transferred by mixed cultivation to E. coli K-12. Multiple resistance of strain 1, and addition, could be transferred to Salmonella typhimurium, Serratia marcescens, Providencia, Proteus mirabilis and Klebsiella pneumoniae in varying frequencies. Transfer to Pseudomonas aeruginosa, however, could not be achieved. Spontaneous instability of resistance was observed in 0.15% of the cells of an overnight brothe culture and in 90% of the cells of a three months old culture. Conjugation, instability and the response to the sex phages MS-2 and If-1 suggested that resistance was mediated by a monomolecular R-factor, belonging to the fi+-type. This suggestion was confirmed by molecular characterization of the resistance plasmids. After transfer of the R-factors of K. pneumoniae 1 (R-FK 1) and Serratia marcescens 2 (R-FK2) into E. coli K-12, plasmid DNA was labelled with (methyl-3H) thymidine, and isolated by isopycnic centrifugation in cesiumchlorid-ethidium-bromide. Analysis of plasmid DNA then was carried out by sedimentation in a 5-20% neutral sucrose gradient together with reference plasmids of known molecular weights and sedimentation constants. The analysis revealed that R-FK1 had a molecular weight of 54 X 10(6) and R-FK2 of 50 X 10(6) daltons. The values were confirmed by contour length measurements of open circular forms with an electron microscope. A comparison of the sedimentation profile of labelled plasmid DNA from strain 1 and 14C-labelled DNA of E. coli K-12 (R-FK1) showed that the wild-type strain contained, besides the large resistance plasmid, at least two smaller "cryptic" plasmids. These smaller plasmid molecules were also found in antibiotic susceptible variants of strain 1, which did not contain the 54 X 10(6) dalton plasmid molecule, responsible for the resistant phenotype. The number of copies of R-FK1 in E. coli K-12 was determined to be 2, indicating stringent control of replication. It is discussed that the growing number of isolations of strains of Escherichia, Klebsiella, Serratia, Proteus, Providencia and Pseudomonas, exhibiting the same resistance phenotype, results from the spread of the R-factor described above among the hospital bacterial flora.

Aminoglycosides↗

Examination of the activities of 43 chemotherapeutic agents against Neospora caninum tachyzoites in cultured cells.

Neospora caninum causes serious disease in dogs, and it, or a similar parasite, is a major cause of abortion in cattle. Little is known about the susceptibility of this protozoan to antimicrobial agents. We studied several antimicrobial agents to determine which classes might have activity against this parasite. We also determined whether activity of such agents was coccidiocidal or coccidiostatic. A 2-day of treatment, monoclonal antibody-based enzyme immunoassay and a 5-day of treatment, cell culture flask (CCF), lesion-based assay were developed to examine the ability of test agents to inhibit tachyzoite multiplication. Seven sulfonamides were examined, with the following activities observed: sulfathiazole > or = sulfamethoxazole > sulfadiazine > sulfaquinoxaline > or = sulfamethazine > sulfadimethoxine > sulfamerazine. Dapsone, a sulfone, had little activity. Six dihydrofolate reductase/thymidylate synthase inhibitors were examined, with the following activities observed: piritrexim > pyrimethamine > ormetoprim > trimethoprim = diaveridine > methotrexate. Six ionophorous antibiotics were examined; lasalocid, maduramicin, monensin, narasin, and salinomycin had equivalent activities, but alborixin was toxic for host cells at the lowest concentration examined. Three macrolide antibiotics--azithromycin, clarithromycin, and erythromycin--were examined and had equivalent activities. Two tetracycline antibiotics, doxycycline and minocycline, were examined and had equivalent activities. Three lincosamide antibiotics were examined, with the following activities observed: clindamycin hydrochloride > clindamycin phosphate > lincomycin hydrochloride. Pentamidine and 6 of its analogs were examined, and only hexamidine and 1,4-Di[4-(2-imidazolinyl)-2-methoxy-phenoxy]butane had activity. Eight miscellaneous antiprotozoal agents were examined for activity. Amprolium, metronidazole, paromomycin, and roxarsone had little activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Giardiasis. Issues in diagnosis and management.

Giardia lamblia is a frequent cause of diarrhea throughout the United States and the world. Advances in basic biology indicate that different strains of Giardia exist, that mammals can be infected with G. lamblia-type organisms, and that secretory IgA is important to host protection. Although water remains the most common mode of transmission of Giardia, there has been an increase in the number of person-to-person cases, especially related to children in day care, as well as an increase in food-borne cases. New antigen detection assays have improved the ability to diagnose Giardia in the stool and make it unlikely that duodenal sampling will be necessary. Metronidazole has become the drug of choice for most cases of giardiasis because of its efficacy, favorable tolerance, and availability. For pregnant women who require treatment, a non-absorbable aminoglycoside, paromomycin, may be tried first and metronidazole used if initial treatment fails.

Adult↗

[Initial clinical experiences with TIPS (transjugular intrahepatic portasystemic stent-shunt)].

15 patients with predominantly alcoholtoxic liver cirrhosis (mean age 50 years; 8 men and 7 women) were treated by the technically successful implantation of a transjugular portosystemic stent-shunt (TIPS) within a period of 1 year. The indications for TIPS implantation were the following: gastroesophageal bleedings in 12 cases (10 patients with recurrent variceal bleeding including 2 emergency cases with severe bleeding resistant to conventional therapy and 2 patients with exclusively gastral bleeding due to severe hypertensive gastropathy) and ascites resistant to conventional therapy in 3 cases. Portovenous pressure could be effectively reduced by mean of 37%. Within a mean observation period of 8 months 13 patients including the emergency cases remained without recurrent bleeding. Duplexsonography showed patent stents. 1 patient suffered from an early recurrent bleeding due to occlusion of the stent-shunt. The estimation of liver function according to the Child-Pugh-classification showed only minor changes. Before TIPS 9 patients were in class A, 4 in B, 2 in C; after TIPS 8 patients in A, 5 in B and 2 in C. Ascites resolved completely. Following TIPS all patients appeared to abstain from alcohol. After TIPS 5 from 14 surviving patients (36%) developed clinically manifest encephalopathy within the first 4-8 weeks (2 patients with previous episodes of encephalopathy, 2 other patients after withdrawal of lactulose). By enhanced conservative treatment (lactulose, paromomycine and protein restriction) encephalopathy could be overcome. 8 from 11 surviving patients investigated displayed characteristic MRI changes with an increased signal intensity in the basal ganglia (T1 weighted images). According to our preliminary results TIPS represents a new successful interventional regimen for the treatment of portal hypertension in selected cases.

Adult↗

New drugs for tuberculosis.

Since the late 1960s, tuberculosis has been successfully cured with antibiotics. With the introduction of rifampin, "short course" regimens using isoniazid and rifampin together with either streptomycin, ethambutol or pyrazinamide, for 6-9 months, have been successfully adopted. The spread of drug resistant M. tuberculosis strains in large urban areas has made this armamentarium of drugs insufficient, calling for the development of new drugs. Among rifamycin derivatives, rifabutin is more active than rifampin in vitro and in experimental animals, and allows sputum conversion rats of 95-100%. It is effective in treating multidrug-resistant tuberculosis. Rifapentine is more active than rifampin in vitro and has a longer half-life, but it is not active against rifampin-resistant strains. Fluoroquinolones concentrate within macrophages, are effective against M. tuberculosis and act synergistically with rifampin and isoniazid. Ofloxacin, ciprofloxacin, sparfloxacin and lomefloxacin have been evaluated as antimycobacterial agents, and no cross-resistance with major antituberculous drugs has been found. Several other drugs, including new inhibitors of beta-lactamase and new beta-lactamase-resistant antibiotics, the aminoglycoside antibiotic, paromomycin, and the new nitroimidazole, 2-ethyl-5-intro-2.3-dihydro imidazo-oxazole, have been found to be active in vitro against M. tuberculosis.

Animals↗