Follow-up of neurocysticercosis patients after treatment using an antigen detection ELISA

Seven patients with active neurocysticercosis (NCC) received an eight days treatment with albendazole and were followed up using computed tomography (CT-scan) and a monoclonal antibody based ELISA for the detection of circulating antigen (Ag-ELISA). Only three patients were cured as was shown by CT-scan and by the disappearance of circulating antigens one month after treatment. After a second course of albendazole therapy, two other patients became seronegative. CT-scan showed the disappearance of viable cysts in all persons who became seronegative whereas patients who were not cured remained seropositive. These preliminary results show that this Ag-ELISA is a promising technique for monitoring the success of treatment of NCC patients because of the excellent correlation between the presence of circulating antigens and of viable brain cysts.     

Cyclophosphamide Therapy in the Nephrotic Syndrome in Childhood

Forty-six children with the nephrotic syndrome whose renal biopsy specimens showed minimal changes and whose response to corticosteroid therapy was unsatisfactory were treated with cyclophosphamide. Three patients were completely steroid-resistant from the outset and the remainder were steroid-dependent. In several patients steroids controlled the condition less effectively with time. Most patients showed signs of steroid toxicity, and growth retardation was striking.A moderate leucopenia was induced with cyclophosphamide, and treatment was maintained for three to four months in the majority of cases. Thirty-eight children (83%) have remained in complete remission off all treatment for periods of 3 to 23 months, 33 after one course of cyclophosphamide and five after a second course. Two other patients who remitted but relapsed later are still on treatment. In only six patients was full remission not obtained, and three of these were steroid-resistant from the start. Two died from pneumonia and adrenal failure and four continued to have proteinuria, though in one an impressive reduction occurred.The results indicate that cyclophosphamide therapy is an effective alternative for nephrotic children with normal glomeruli on light microscopy who develop steroid dependence or resistance, and who exhibit toxic effects of steroid therapy.     

Plasmodium knowlesi: Morphology and course of infection in rhesus monkeys treated with clindamycin and its N-demethyl-4′-pentyl analog

The clinical and morphologic effects of clindamycin and N-demethyl-4′-pentyl clindamycin were evaluated using Plasmodium knowlesi in rhesus monkeys. Both compounds cured blood-induced infections when administered daily for five consecutive days. When the rapidity of action of these antibiotics was compared with chloroquine it was evident that although they were able to control fulminating infections in all treated monkeys their effect was about 2 days slower than chloroquine in decreasing parasitemias and 3 to 4 days slower in clearing parasites from the blood. Morphologic changes within the parasite associated with drug action were studied in time sequences by light and electron microscopy. Changes were observed in the parasite ribosomes 24 hr after drug administration. Affected ribosomes showed electron-lucent zones measuring ~50 Å in the center. During the following 24 hr these changes became more prominent with foci in which disintegrated ribosomes were replaced by fine fibrillar material and the cisternae of the endoplasmic reticulum became dilated. By 72 hr this dilation was more apparent and resulted in abundant coalescence of vacuoles in the cytoplasm. Mitochondria became dilated with fibrils in the matrix, although the degree of swelling was not a conspicuous and constant feature. The nucleus presented a fine fibrillar appearance and fewer granules were seen than in normal parasites. The latter two observed changes appear to be secondary to changes in the ribosomes and probably are not directly related to the action of the antibiotics. These studies indicate that clindamycin and its analog affect primarily the ribosomes and their mode of action is different from that of the commonly used antimalarials.     

Gutter treatment for ingrowing toenails.

The gutter treatment for ingrowing toenails consists of introducing a small guard along the side of the toenail and requires only three outpatient attendances. The gutter is left in place for eight to 12 weeks and then removed by the patient. Two studies were carried out to establish the long-term results of the method. In one, a preliminary retrospective study, 13 out of 25 patients who had received the gutter treatment were cured after one year compared with five out of 15 patients in whom the toenail had been avulsed. In a randomised prospective study 20 out of 36 patients (56%) treated by the gutter method were cured after one year compared with 27 out of 32 (84%) in whom the wedge resection procedure had been used. The gutter treatment demands little skill and may be carried out in general practice. It gives an excellent cosmetic result with immediate pain relief and does not compromise further surgery should this be required, thus fulfilling the main requirements for the primary treatment of choice.     

Pseudomembranous Enterocolitis: Resurgence Related to Newer Antibiotic Therapy

Six patients with pseudomembranous entercolitis were seen at one institution over a six-month period. Clindamycin therapy preceded the diagnosis in all six patients and possibly caused the disease in five cases. Common clinical features included diarrhea, abdominal pain, fever, leukocytosis, radiographic findings of large bowel dilatation with mucosal thickening and a characteristic sigmoidoscopic or gross pathologic demonstration of discrete yellow-white plaques on an otherwise normal mucosa. Complications included toxic megacolon and sigmoid colon perforation. Two of the six patients died. The literature since 1970 is tabulated to clarify the clinical and pathological features of pseudomembranous enterocolitis associated with newer antibiotic therapy. Lincomycin and clindamycin are strongly implicated in the recent resurgence of this formerly rare variety of colitis.     

Combination antibiotic therapy in an outbreak of prosthetic endocarditis caused by Staphylococcus epidermidis.

The efficacy of combination antibiotics in vivo and in vitro was studied during an outbreak of prosthetic endocarditis caused by Staphylococcus epidermidis in 10 patients. The epidemic curve suggested that patients were infected at the time of their operation, with an interval from that time until diagnosis of 11 days to 20 months. The overall mortality was 50%. Four of six patients treated with gentamicin in combination with a penicillin analogue, a cephalosporin or clindamycin survived without reoperation. One of four patients survived when treated with regimens that did not include gentamicin. In vitro studies showed a median minimum inhibitory concentration for methicillin of 8.0 microgram/mL, compared with 0.1 microgram/mL for cephalothin, clindamycin and gentamicin, and a synergistic bactericidal effect between gentamicin and methicillin, cephalothin or clindamycin. These data suggest that gentamicin is a valuable component of combination antibiotic therapy in prosthetic endocarditis caused by S. epidermidis.     

Subacute bacterial endocarditis; a report on 57 patients treated with massive doses of penicillin

Fifty-seven patients with subacute bacterial endocarditis were treated with doses of penicillin varying from 500,000 to 20,000,000 units per day. Diagnosis was confirmed in some cases by growths on blood culture, in others by postmortem examination. In those cases in which the diagnosis was established by blood culture, the in vitro sensitivity of the organism to penicillin was determined and penicillin then was administered by continuous intramuscular infusion in a dosage calculated to produce blood levels of penicillin four to five times that required for in vitro inhibition. Penicillin was given for a period of 21 days, and blood cultures were made periodically during and after treatment. Of the 57 patients, 38 were cured (66.7 per cent), and 19 died (33.3 per cent). Of the 19 who died, three did so within 48 hours of hospitalization and seven died despite adequate treatment. Of these seven, three died of cerebral emboli, two because of resistance to penicillin and streptomycin, one because of congestive heart failure, and one of undetermined cause. The remaining nine who died were considered to have been inadequately treated in that there was (1) failure to obtain sensitivity, (2) inadequate dossage of penicillin, (3) delay in starting treatment, or (4) failure to recognize mixed infections. There were five patients with repeatedly sterile blood cultures during life. In all of these cases, streptococcus viridans was recovered at postmortem examination. In an attempt to determine how long therapy should justly be withheld in patients with repeatedly sterile blood cultures, 140 cases of subacute bacterial endocarditis in which positive blood cultures had been obtained were reviewed. From the review it was determined that if blood cultures taken during the first two days are reported sterile, the chance of subsequent cultures proving positive is minimal. Therefore, for patients in whom the diagnosis seems otherwise obvious, delaying treatment for more than two days is not justified even though the blood culture be sterile. In cases in which blood cultures are repeatedly sterile, a dosage of 6,000,000 to 10,000,000 units of penicillin daily for 21 days is advisable.High bacterial resistance to penicillin and streptomycin was found in four fatal cases. In one of these, the infecting organism was streptococcus viridans, and in three it was staphylococcus albus. There was one patient with penumococcal meningitis complicated by unrecognized streptococcal viridans bacterial endocarditis.     

SUBACUTE BACTERIAL ENDOCARDITIS—A Report on 57 Patients Treated with Massive Doses of Penicillin

Fifty-seven patients with subacute bacterial endocarditis were treated with doses of penicillin varying from 500,000 to 20,000,000 units per day. Diagnosis was confirmed in some cases by growths on blood culture, in others by postmortem examination. In those cases in which the diagnosis was established by blood culture, the in vitro sensitivity of the organism to penicillin was determined and penicillin then was administered by continuous intramuscular infusion in a dosage calculated to produce blood levels of penicillin four to five times that required for in vitro inhibition. Penicillin was given for a period of 21 days, and blood cultures were made periodically during and after treatment.Of the 57 patients, 38 were cured (66.7 per cent), and 19 died (33.3 per cent).Of the 19 who died, three did so within 48 hours of hospitalization and seven died despite adequate treatment. Of these seven, three died of cerebral emboli, two because of resistance to penicillin and streptomycin, one because of congestive heart failure, and one of undetermined cause. The remaining nine who died were considered to have been inadequately treated in that there was (1) failure to obtain sensitivity, (2) inadequate dossage of penicillin, (3) delay in starting treatment, or (4) failure to recognize mixed infections.There were five patients with repeatedly sterile blood cultures during life. In all of these cases, streptococcus viridans was recovered at postmortem examination. In an attempt to determine how long therapy should justly be withheld in patients with repeatedly sterile blood cultures, 140 cases of subacute bacterial endocarditis in which positive blood cultures had been obtained were reviewed. From the review it was determined that if blood cultures taken during the first two days are reported sterile, the chance of subsequent cultures proving positive is minimal. Therefore, for patients in whom the diagnosis seems otherwise obvious, delaying treatment for more than two days is not justified even though the blood culture be sterile. In cases in which blood cultures are repeatedly sterile, a dosage of 6,000,000 to 10,000,000 units of penicillin daily for 21 days is advisable.High bacterial resistance to penicillin and streptomycin was found in four fatal cases. In one of these, the infecting organism was streptococcus viridans, and in three it was staphylococcus albus. There was one patient with penumococcal meningitis complicated by unrecognized streptococcal viridans bacterial endocarditis.     

Therapeutic experience with netilmicin.

Netilmicin, a new aminoglycoside antibiotic, was used to treat 19 patients with urinary tract infection and 5 with systemic infection. The causal organisms were Escherichia coli (in 2), Klebsiella pneumoniae (in 4), Serratia marcescens (in 12) and Pseudomonas aeruginosa (in 7); 1 patient was infected with two of these organisms. All the isolates of causal organisms except one of Serratia were initially sensitive to netilmicin but many were resistant to other aminoglycosides. Sixteen of the urinary tract infections responded to netilmicin therapy, although relapse occurred in three patients. Two of the three patients with musculoskeletal infection responded to combined therapy with surgery and netilmicin; the other patient responded to the same regimen but with carbenicillin added. Netilmicin cured pneumonia in one patient but failed in the other patient with pneumonia, who had leukemia. Superinfection occurred in five patients with urinary tract infection. Adverse reactions to netilmicin were minor. Netilmicin may prove to be a useful agent, particularly for infections due to multiresistant Klebsiella or Serratia, or when prolonged aminoglycoside therapy is required.     

Clindamycin plus gentamicin as expectant therapy for presumed mixed infections.

The prevalence of obligate anaerobes was studied prospectively in 60 patients with severe sepsis of intra-abdominal, soft tissue, female genital or oropulmonary origin. In addition, the efficacy of clindamycin (for anaerobes) plus gentamicin (for aerobic bacteria, especially coliforms) as initial empiric therapy in these patients was evaluated. Among 54 patients with cultural proof of infection, anaerobic pathogens were recovered from 52%. Nineteen patients had bacteremia; Bacteroides fragilis and Klebsiella pneumoniae were the most prevalent pathogens, being isolated in five patients each. Infection was eradicated in 56 of the 60 patients (93%). Mortality related to sepsis was 7% in the entire group, 16% in patients with bacteremia and 2% in patients without bacteremia. Eighty-five percent of aerobic isolates tested were susceptible in vitro to either gentamicin or clindamycin; 97% of anaerobic isolates were inhibited by 5 mug/ml of clindamycin.     

NITROFURANTOIN (FURADANTIN?)—Use of Intravenous Forms in Resistant Surgical Infections; a Preliminary Report on 25 Patients

Twenty-five patients with severe and unusually resistant bacterial infections were treated with nitrofurantoin given intravenously.Twelve patients were classified as cured and seven as improved. In two cases there was no observable benefit. The other four patients, all moribund at the beginning of nitrofurantoin therapy, died. No significant toxic reaction to the drug was noted except for a tendency to metabolic acidosis in five patients in a state of shock after treatment with nitrofurantoin (Furadantin® intravenous solution). In no case was there evidence of impaired hematopoiesis.From this preliminary report it appeared that nitrofurantoin for intravenous use is justified in the treatment of gravely ill patients with surgical infections resistant to other antimicrobial drugs.     

Eficacia del econazol en embarazadas con candidiasis vulvo-vaginal

Among the female patients attending the out patient clinic of the Obstetric Service of the University Hospital of Caracas, Venezuela a hundred were chosen who presented vaginal discharge and itching. The presence of C. albicans and the existence of candidiasis in the vulvo-vagina of the 100 pregnant women was investigated. Those patients where candidiasis was found, were also investigated as to the simultaneous presence of C. albicans in the mouth and the anal skin. Gyno-Pevaryl therapy was performed by administering one 150 mg ovule daily for three consecutive days. At the same time, their partners were treated with Pevaryl 1% cream. The post-therapy control was made 36 hours after conclusion of treatment and further check-up were made one week and two weeks later. Only those patients who attended the post-treatment controls were taken into account for the evaluation of the results. C. albicans was identified in 60 cases by nascent culture of the vulvar secretions, using a bile-agar medium. Of these, 50 had vulvo-vaginal candidiasis (hyphae and blastospores on direct examination). 92% of the women with vulvo-vaginal candidiasis complained about pruritus at the moment of the examination. No significant differences were observed with respect to the age, the period of gestation and parity of the positive and negative patients. Of the 40 patients who attended only the first control, 23 were cured (57.5%), 9 improved (22.5%) and 8 (20%) were not cured. The cure rate increased to 70% and 72.5% taking into account those patients, who also attended the second and the third consecutive treatment sessions, respectively. In those patients suffering from vulvo-vaginal candidiasis, 37.5% were found to be carriers of C. albicans in the mouth and 70% also in the anal region. This seems to indicate that the mouth and the anal region can constitute the source of re-infection in the majority of the cases following topical vaginal treatment.     

METHYL-BIS (BETA-CHLOROETHYL) AMINE IN LARGE DOSES IN THE TREATMENT OF NEOPLASTIC DISEASES

Sixty-seven patients with neoplastic diseases were treated with 151 courses of methylbis (beta-chloroethyl)amine hydrochloride (HN₂). Seventy-seven of the courses consisted of single injections of 0.2 to 0.4 mg. per kilogram of body weight, and 35 courses were given as single injections of 0.6 mg. per kilogram of body weight.Twenty-three patients with Hodgkin''s disease were treated. Remissions averaged approximately three months in 13 patients who were in good or fair general physical condition, and 1.5 months in 11 patients who were in poor or moribund condition; one of the 11 did not respond to the therapy.Fifteen patients with lymphosarcoma were treated. Remissions averaged between one and two months in four patients who were in good or fair general physical condition. Of the remaining 11 patients, two showed no response, and the longest remission among the remaining nine was approximately 40 days.Satisfactory remissions of one to three months were obtained in four patients with mycosis fungoides treated with single courses of 0.3 mg. per kilogram of body weight.Serious toxic reactions were observed in six patients, four of whom died. In five of the six instances the reactions consisted of pancytopenia and hemorrhagic diathesis. All these patients were in poor general or hematologic status before therapy.In general, large single doses of HN₂ were neither more nor less effective than the four-to six-day course usually employed with this agent. Combination of the administration of HN₂ with artificial hyperpyrexia, or with concurrent courses of pteroylglutamic conjugates, did not enhance the therapeutic effects of the agent.     

Propionibacterium acnes in the etiology of endocarditis]

Propionibacterium acnes is the gram positive anaerobic bacteria belongs to the normal skin and oral microbial flora. The participation of this microorganism in the infective endocarditis is still controversial. The aim of the study was to perform the diagnostic and therapeutic difficulties in 5 patients with infective endocarditis caused by Propionibacterium acnes. In 3 out of 5 patients the infective endocarditis developed after prosthesis valve replacement, in 2 others on the native valves. The inserted prostheses were mechanical ones, propionibacterium acnes was identified as causative organisms in all of the causes (two positive blood and/or valve culture). The bacterial strains were sensitive to the antibiotics as: penicillins, cephalosporins, clindamycin, and vancomycin, however cephalosporins used at the beginning of the treatment in 3 patients and clindamycin in 1 patient had limited clinical efficacy. Later treatment with timentin, augmentin and tienamycin was successful in 3 patients; one patient was cured with vancomycin. One patient died because of septic, embolic complication in early stage of illness. We conclude the effectiveness of penicillins in combination with clavulanic acid and tienamycin in therapy of infective endocarditis due to Propionibacterium acnes. The treatment should be lasted during 4-6 weeks.     

In vitro biocompatibility of denture relining materials

Objective: The aim of the present study was to evaluate the in vitro biocompatibility of denture relining materials using cell culture tests and a test for irritation mechanisms. Background: Denture relining materials contain non‐reacted constituents that may leach out during use inducing local toxic or irritative effects. Materials and methods: One chemically cured, four visible light cured and five dual‐cured products were included. Cured test specimens were used for the filter diffusion test, and extracts of cured specimens were applied in the MTT and the irritation test using the hen's egg test‐chorioallantoic membrane (HET‐CAM) method. Results: Five of the tested materials were slightly or moderately cytotoxic in the filter diffusion test, and one product coated with a liner induced severe toxicity. Cell cultures incubated for 24 hour with the test samples were more damaged than those incubated for 2 hour. In the MTT test, extracts of nine of the 11 products induced cytotoxicity. No extracts showed irritation, whereas the coating and two bonding agents tested were strong irritants. Conclusion: Most of the tested materials contained water soluble, toxic substances that leach out of the products and that some time was needed to obtain cytotoxic amounts of the leachables. Many dental materials elicit cytotoxic response, but this does not necessarily reflect the long‐term risk for adverse effects as the oral mucosa is generally more resistant to toxic substances than a cell culture.     

Use of denaturing gradient gel electrophoresis for analysis of the stool microbiota of hospitalized patients

Denaturing gradient gel electrophoresis (DGGE) of PCR-amplified ribosomal RNA gene amplicons was used to study the stool microbiota of hospitalized patients and to examine the effect of antibiotic therapy. For one patient, 16 anaerobic species identified by random cloning and sequencing of PCR-amplified rRNA genes from stool were represented by bands on the DGGE gel. DGGE analysis and similarity index comparisons demonstrated that the anaerobic microbiota of this individual remained stable in the absence of antibiotic therapy, was minimally affected by ciprofloxacin but markedly reduced by clindamycin therapy, and recovery of some organisms was evident within days after discontinuation of clindamycin. DGGE analysis of additional patients demonstrated similar disruptions of the intestinal microbiota associated with antibiotic therapy. The DGGE banding patterns of nine patients showed considerable variability, but several bands were shared among patients. Thus, our findings are consistent with previous studies that utilized culture techniques, and suggest that DGGE is a useful technique for analysis of the stool microbiota of hospitalized patients.     

Propranolol in the Control of Schizophrenic Symptoms

All schizophrenic symptoms remitted completely in six out of 14 adults who had not responded to phenothiazine drugs and who were then given propranolol. Another patient improved markedly and four improved moderately. Two had minimal or transient improvement, and one left hospital unchanged after a short, severe, toxic reaction. The six with complete remissions all began to improve within a few days of starting propranolol and the florid symptoms remitted completely after three to 26 days. They were stabilized on a daily dose of 500-3,500 mg of propranolol and at the time of writing had remained well for up to six months. Two patients who stopped propranolol after their symptoms remitted relapsed severely within a few days. Toxic effects (ataxia, visual hallucinations, and confusional states) were related to the rate of increase rather than to the absolute dose of propranolol. After the procedure was modified unwanted effects were usually mild or absent.     

骨嗜酸性肉芽肿放射治疗临床分析

目的：探讨骨嗜酸性肉芽肿的治疗方法。方法：对近5年来我院收治经病理证实的12例骨嗜酸性肉芽肿的治疗进行临床回顾性研究。结果：随访1．5a～6a,其中11例患者行局部肿块刮除和放射治疗30Cy后治愈,1例复发,行再程治疗后治愈,总有效率为100％。结论：骨嗜酸性内芽肿治疗采用手术局部肿块刮除和放射治疗,可取得良好效果。     

Long survival in acute myelogenous leukaemia: an international collaborative study.

A group of 82 adult patients with acute myelogenous leukaemia had survived in continuous first remission for more than three years was studied. These long-surviving patients were being treated at 12 referral centres in Europe and the USA, and they were compared with other patients with acute myelogenous leukaemia from 10 of these centres. There was no clear difference in the amount of induction chemotherapy or the time taken to achieve remission. Immunotherapy was not found to improve chances of long-term survival. The 82 patients were also compared with a group of 115 patients who had no appreciable difference in the number of blood or marrow myeloblasts between these two groups at presentation, but the long survivors had significantly higher initial platelet counts and were slightly younger. The long survivors also tended to have a lower total white cell count at presentation and lower granulocyte counts; there was no obvious explanation for these differences. Eight of the 82 patients relapsed from three to four years after remission and two (of 69 patients) after four to five year. Thereafter relapse was rare, and it seems likely that some of the 40 patients who have survived for five years or more are cured.     

Plasmodium berghei: Development of resistance to clindamycin and minocycline in mice

Strains of Plasmodium berghei resistant to clindamycin or minocycline were selected by a procedure in which groups of infected mice were treated with increasing doses of drug during each of a series of subpassages. Groups of five mice, each infected by intravenous inoculation with 10 million parasitized erythrocytes, were treated orally with different doses of drug for four consecutive days beginning on the day of infection. Subpassages were routinely made by Day 7, using donor mice from the group that had been treated with the highest dose of drug that allowed for some development of parasitemia during the preceding passage. Drug doses were increased in each passage as dictated by the development of parasitemia during the previous treated passage.The rate of development of resistance to clindamycin or minocycline was much slower than to conventional antimalarials such as chloroquine, quinine, or pyrimethamine. P. berghei developed total resistance to the latter compounds in nine to 12 treated passages in mice over a period of 60 to 85 days. In contrast, development of total resistance to clindamycin required 42 treated passages over a period of 300 days. Total resistance to minocycline was not attained during 86 successive minocycline-treated passages in mice over a period of 600 days, but a sixfold increase in resistance to minocycline was observed.The clindamycin-resistant strain was normally sensitive to minocycline, chloroquine, quinine, and pyrimethamine. The strain partially resistant to minocycline was normally sensitive to clindamycin, chloroquine, quinine, and pyrimethamine. Resistance to clindamycin was stable during 51 drug-free passages in mice over a period of 1 year. Resistance to minocycline was unstable. During 16 drug-free passages in mice the strain reverted towards normal sensitivity to minocycline. Strains resistant to clindamycin or minocycline showed no difference in rate of development in mice as compared to the parent strain. Likewise, only minor morphological modifications were seen in Giemsa-stained blood smears between the two resistant strains and the parent strain.These results suggest that other species of malaria may develop resistance to clindamycin or minocycline. Should resistance to one of these compounds appear, however, it should not invalidate the use of the other in the treatment of malaria.