Cytogenetic effects on lymphocytes in osteoporotic patients on long-term fluoride therapy

The genotoxicity of fluoride in vivo in seven patients with osteoporosis was cytogenetically investigated. The patients were treated with fluoride-containing formulations (disodium monofluorophosphate and sodium fluoride) for a period of 15 months up to 49 months. Fluoride intake ranged from 22.6-33.9 mg F/day and serum fluoride concentrations were between 0.1 mg F/l and 0.2 mg F/l. Peripheral blood lymphocytes of these patients were cultured in vitro and examined for chromosomal aberrations, micronuclei in cytokinesis-blocked binucleated lymphocytes as well as cell cycle progression. When a comparison was made between patients' group and a matched control group, it was found that fluoride at the tested concentrations had no detectable genotoxic potential in human.     

Time-dependent hemodynamic effects of monosan (Isosorbide-5-mononitrate) in anginal patients

Clinical efficacy of 3rd generation cephalosporins i.e. oral cefpodoxime and parenteral ceftriaxone was studied in the treatment of children with oncohematologic pathology. Cefpodoxime proved to be efficient in cases of moderate infectious complications in regard to the respiratory tracts. The oral administration of the drug provided its usage in outpatients. Ceftriaxone had a favourable effect in the treatment of children with more severe processes as a rule at the background of agranulocytosis and a lower immune response often with a tendency to generalization. No side effects of the cephalosporins were observed.     

Pathologic features of spinal disorders in patients treated with long-term hemodialysis

STUDY DESIGN: Pathologic features of hemodialysis-associated spinal disorders were evaluated using preoperative radiographic images and histologic findings of the spinal lesions resected during surgery. OBJECTIVES: To investigate the pathology of hemodialysis-related spinal disorders and to determine the role of amyloidosis in the establishment of severe destruction of the spine. SUMMARY OF BACKGROUND DATA: The pathologic events leading to hemodialysis-associated spinal disorders are poorly understood. The distribution of amyloid deposits in the spine also has not been clarified. METHODS: Twenty patients with hemodialysis-associated spinal disorders were investigated regarding pathologic features of neural compression and spinal destruction. Preoperative radiographic images such as plain radiography, tomography, computed tomography, magnetic resonance imaging, and scintigraphy were assessed for the existence of an intracanal mass, hypertrophy of the ligamentum flavum, and destructive changes of the spinal components. Histologic examination also was conducted by light microscopy and scanning electron microscopy to determine the distribution pattern of amyloid deposits in the spinal components. RESULTS: Six patients with no destructive changes in the spine showed spinal canal stenosis. In the cervical spine, a main factor associated with spinal canal stenosis was the presence of intracanal amyloid deposits in three patients. In the lumbar spine, a main factor associated with spinal canal stenosis was hypertrophied ligamentum flavum in three patients. Destructive changes of the facet joints, intervertebral disc, and vertebral body were seen in the other 14 patients. Amyloid deposits were densely distributed at the enthesis of capsular fibers to the bone and in anular tears in the intervertebral discs. Vertebral end plates were destroyed by penetration of amyloid granulation into the vertebral body. Osteoclast activity in the destroyed vertebral bodies was enhanced, with no evidence of new bone formation. CONCLUSIONS: Amyloid deposits played an important role in the progression of spinal destruction and severe instability.     

Oral DMSO therapy in 3 patients with lipoidproteinosis. Results of long-term therapy

Lipoid proteinosis is a rare autosomal recessive disorder with a chronic, benign course. There is no generally accepted systemic therapy apart from the experimental oral use of dimethyl sulphoxide (DMSO) and etretinate in two single cases. We treated two sisters and an unrelated man with lipoid proteinosis with longterm oral DMSO (60 mg/kg/d). At the end of an average treatment time of 3 years, DMSO was withdrawn because it produced no beneficial effects with regard to their skin, mucosal lesions or hoarseness. Additionally, one patient showed progression of her disease with worsening hoarseness and onset of dyspnea, requiring surgical removal of vocal cord infiltrates. Three patients with lipoid proteinosis failed to show any beneficial response to long term treatment with DMSO.     

Bomocriptine treatment of patients with acromegaly resistant to conventional therapy

Eleven patients with active acromegaly resistant to conventional therapy were treated with bromocriptine for 15 (12--22) months by increasing the daily dose stepwise from 5 to 10--60 mg. A satisfactory response was achieved in all but one of the eight patients, in whom the mean diurnal level of serum GH was less than 50 ng/ml, whereas patients with grossly elevated serum GH levels responded poorly. In the longterm, no overall effects on glucose tolerance or plasma insulin (IRI) levels were observed but the chemical diabetes of three patients ameliorated in two. On the other hand, a dose-dependent acute suppressive effect of bromocriptine on plasma IRI response to oral glucose was observed, suggesting a direct effect of bromocriptine on the release of insulin from beta cells. Bromocriptine seems to be a good alternative in the treatment of patients with acromegaly who have not responded to conventional therapy.     

Bone mineral density in patients on long-term therapy with levothyroxine

The aim of the study was to determine the influence of replacement and suppressive thyroxine therapy on bone mineral density (BMD). 30 postmenopausal women; 19 on replacement therapy (dose 1.22 +/- 0.35 micrograms/kg; duration 11.4 +/- 7.2 years) and 11 on suppressive therapy (dose 1.45 +/- 0.71 micrograms/kg; duration 9.5 +/- 7.2 years). Controls were 60 healthy women matched for age and menopausal status. BMD at the lumbar spine (L2-L4), femoral neck, Ward's triangle and trochanter was measured by dual-energy absorptiometry. Forearm BMD at distal site was measured by single-photon absorptiometry. Mean thyroid hormone values and TSH were within normal limits, although the patients on suppressive therapy had significantly higher T3 (p < 0.05) than the patients on replacement therapy. BMD on each site was significantly lower in the replacement treated group than in controls. BMD in patients on suppressive therapy was lower, but not significantly, compared to controls. Thyroxine therapy could have an adverse effect on BMD. The magnitude of bone loss depends on the serum level of thyroid hormones and on the functional state of thyroid hormone receptor in bone tissue, as well.     

Mortality in depressed patients treated with electroconvulsive therapy and antidepressants

The treatments of 519 depressed patients hospitalized from 1959 to 1969 were compared in a three-year follow-up study with particular reference to mortality. The electroconvulsive therapy (ECT) group had a significantly lower mortality than the inadequate antidepressant treatment group (P less than .05) and the group that received neither ECT nor antidepressants (P less than .025). Although the adequate antidepressant treatment group had a low mortality, statistically significant differences between this and other treatment groups could not be documented. Nonsuicidal deaths (P less than .005), and particularly myocardial infarctions (P less than .01), were significantly more frequent in the inadequately treated group compared to the adequately treated group. The superiority of adequate treatment is especially striking among men and among the older age groups. The results underscore the importance of adequate treatment of depression, especially in the older man.     

Survival of patients with carcinoma of the esophagus treated with combined-modality therapy

Since 1985, 229 cases of carcinoma of the esophagus have been considered for entry into a protocol with the use of preoperative chemotherapy and radiation therapy followed by surgical intervention as the primary element of treatment. One hundred sixty-five patients (93 with adenocarcinoma and 72 with squamous cell carcinoma) had esophagogastrectomy. The 5-year survival of the protocol patients who underwent resection was 25% for both groups--squamous cell carcinoma and adenocarcinoma. Of the protocol patients with squamous cell carcinoma who underwent resection, 40% had a sterilized specimen, whereas of those with adenocarcinoma, 20% had a sterilized specimen. If the patient had a sterilized specimen, the 5-year survival was approximately 60% for adenocarcinoma and 40% for squamous cell carcinoma. Those patients with adenocarcinoma and Barrett's esophagus had a 5-year survival of 55%. Of the patients who underwent only esophagectomy and esophagogastrectomy and had not been entered into the protocol, none lived beyond 3 years. The operative mortality rate for those who had esophagogastrectomy was 5%. Sixty-four patients completed the radiation therapy and chemotherapy but did not undergo surgical procedures because of progressive disease or refusal. Of those patients who completed chemotherapy and radiation therapy without surgical intervention, 5-year survival was 18% in patients with squamous cell carcinoma, whereas no patients with adenocarcinoma survived beyond 3 years. The finding of a sterilized specimen after esophagectomy is a favorable prognostic factor in patients with adenocarcinoma or squamous cell carcinoma. The finding that patients with Barrett's esophagus and adenocarcinoma have an improved chance for survival is perhaps related to an earlier diagnosis. It is clear that some patients with squamous cell carcinoma who did not undergo surgical procedures did have a sterilized specimen, because the survival in this group approached 20% at 5 years.     

Nocturnal blood pressure elevation in patients with type 1 diabetes receiving intensive insulin therapy compared with that in patients receiving conventional insulin therapy

Studies have shown that type 1 diabetic patients may suffer from nocturnal elevation in blood pressure and that this elevation may be related to hyperinsulinemia. In this study we tested the hypothesis that tight type 1 diabetes control, which is usually accompanied by hyperinsulinemia and subclinical nocturnal hypoglycemia, may result in a higher rise in nocturnal blood pressure compared with conventional type 1 diabetes control. Eighteen patients treated with intensive insulin therapy (multiple daily injections; IIT) were compared with 18 patients treated with conventional insulin regimens (twice daily injections of regular and intermediate acting insulin; CIT). Both groups were matched for age, sex, duration of diabetes, body weight, body mass index, baseline daytime blood pressure, and microalbuminuria levels. Hemoglobin A1c was lower in the IIT group compared with that in the CIT group (8.1 +/- 1.2% vs. 11.0 +/- 3.2%; P < 0.01). The amount of insulin/body weight (units per kg) was higher in the IIT group than that in the CIT group (1.0 +/- 0.2 vs. 0.7 +/- 0.2 U/kg; P < 0.05). In all patients, a 24-h ambulatory blood pressure was recorded. The nocturnal diastolic blood pressure was higher in the IIT group (66 +/- 9 mm Hg) than in the CIT group (55 +/- 4 mm Hg; P < 0.01). The nocturnal decline in both systolic and diastolic blood pressure was lower in the IIT group (7 +/- 5 and 6 +/- 4 mm Hg, respectively) compared with that in the CIT group (13 +/- 6 and 16 +/- 6 mm Hg, respectively; P < 0.01). The nocturnal heart rate was higher in IIT group than in the CIT group (81 +/- 12 vs. 67 +/- 9/min; P < 0.05). These findings show that the intensive insulin therapy regimen may have a more deleterious effect than the conventional insulin therapy regimen on the nocturnal blood pressure of patients with type 1 diabetes.     

Incidence of acral nodulosis with long-term methotrexate therapy in patients with inflammatory rheumatic diseases

The significance of acral nodulosis under methotrexate therapy is still controversial. Among patients with rheumatoid arthritis and methotrexate therapy this manifestation could be observed in 8/163 (5%). All cases were seropositive and already treated with other LAAD. Patients with other inflammatory rheumatic diseases under methotrexate therapy (n = 83) did not develop this nodulosis. The acral nodulosis is interpreted as a typical side-effect of methotrexate only in patients with rheumatoid arthritis. Histopathologically, these nodules do not differ from the typical rheumatoid nodule.     

A long-term outcome study of 170 surgically treated patients with compressive cervical radiculopathy

BACKGROUND: There is a general impression that publications in neuro-surgical journals have comprehensively evaluated the relative merits of various operative techniques with long-term follow-up in patients treated for compressive cervical radiculopathy. However, in some 20,000 neurosurgical papers over the past 50 years, only 74 (0.3%) have addressed this common surgical problem. METHODS: Long-term outcome was assessed by the standardized Functional Economic Outcome Rating Scale of Prolo. Information was obtained primarily by telephone interviews and office visits. No patients were operated upon without a confirmatory neuroradiologic study. Single level soft discs were removed through a posterior-lateral foraminotomy with hemilaminectomy or laminectomy the root was decompressed by the same technique with hard discs. RESULTS: One hundred seventy patients were operated on from 1959-91 with a 96% follow-up. The mean follow-up period was 15 years. Patients who had sedentary occupations and housewives, had statistically higher Economic Prolo scores (p < 0.001) than those who did strenuous work. Of 10 patients with a total Prolo score of 5 or less, seven did strenuous work and had Workers' Compensation claims; the remaining had legal claims or were at psychologic risk for operation. In 86% of patients outcome was good; defined as a Prolo score of 8 in 5%, 9 in 38%, and 10 in 43%. Of 10 recurrences (6%), seven occurred within 3 years after operation and were treated by discectomy and anterior cervical fusion. There were two patients with postoperative deltoid motor weakness who recovered within 1 year. CONCLUSIONS: Although outcome studies must have subjective criteria, the Prolo Scale is more objective and quantitative than currently used methods. The posterior approach to disc lesions causing compressive cervical radiculopathy should be compared to other techniques using the Prolo Outcome Scale.     

Cytomegalovirus preemptive therapy with ganciclovir in renal transplant patients treated with OKT3

In an attempt to decrease the prevalence and severity of cytomegalovirus (CMV) disease, preemptive therapy with ganciclovir was administered to all renal transplant patients treated with OKT3 between February 1993 and December 1994 (26 patients). The results were compared with those of a historical group treated with OKT3 but not with ganciclovir (29 patients). Both groups were similar in age, sex, number of previous transplants, number of rejections, serological status of donor and recipient and OKT3 dose. Ganciclovir was administered during the period of treatment with OKT3. Only 2 (7.7%) treated patients developed CMV disease versus 11 (37.9%) of the control group (p = 0.01). In the control group the intensity of the disease was severe in 7 (63.6%) cases, whereas in the treated patients it was always of slight intensity (p = 0.01). In conclusion, preemptive therapy with ganciclovir during treatment with OKT3 decreases the prevalence and severity of CMV disease.     

Dual resistance to zidovudine and lamivudine in patients treated with zidovudine-lamivudine combination therapy: association with therapy failure

Human immunodeficiency virus type 1 (HIV-1) strains dually resistant to zidovudine and lamivudine (3TC) may arise during zidovudine-3TC combination therapy. The objective of this cross-sectional study (n = 43 patients) was to test the association between therapy response (clinical and immunologic) to zidovudine-3TC and the level of phenotypic zidovudine resistance and zidovudine resistance-associated genotype of 3TC-resistant isolates. Other variables included were baseline CD4+ cell count, baseline Centers for Disease Control and Prevention (CDC) classification, virus load, and time receiving zidovudine. Phenotypic resistance was assessed using a recombinant virus assay. Genotypic analysis was based on population sequencing of plasma HIV-1. In a univariate analysis using a logistic regression model, it was found that therapy response was significantly associated with phenotypic and genotypic zidovudine resistance, baseline CD4+ cell count, and virus load. After adjustment for all variables, phenotypic resistance to zidovudine remained the only significantly associated factor, independent of baseline CD4+ cell count, baseline CDC classification, and virus load.     

Short- and long-term outcome of patients treated with cyclosporin for severe acute ulcerative colitis

The effect of core material properties on the process of compression and physical properties of compression-coated tablets were investigated using microcrystalline cellulose as the coating material (mantle). Three model core materials: borosilicate glass, silicone rubber, and steel, each of different Young's modulus, were selected to give a range of core mechanical properties. Coated tablets were prepared using a single-punch press, with facilities for monitoring the compression cycle and analysis of data using the Heckel (1) equation. This analysis showed a considerable effect of different core materials on the compression process, (i) as an unanchored core, and (ii) due to core material type with differing Young's modulus.     

Trazodone and valproate in patients discontinuing long-term benzodiazepine therapy: effects on withdrawal symptoms and taper outcome

Dithiocarbamate compounds are widely used agricultural fungicides that display low acute toxicity in mammals and that may become neurotoxic after prolonged exposure. Mancozeb, among other dithiocarbamates tested, proved to be the most potent (Ki= 0.27 microM) at noncompetitively inhibiting the in vitro ATP-dependent uptake of [3H]glutamate in rat cortical vesicles. Furthermore, mancozeb partially (20%) inhibited the ATP-dependent uptake of [14C]methylamine, used as an index for the vesicular transmembrane proton gradient (DeltapH), and evoked its efflux from organelles previously incubated with the 3H-labeled marker. Meanwhile, the vesicular uptake of 36chloride- anions whose concentrations regulate the transmembrane potential gradient (DeltapsiSV) was not impaired. The dithiocarbamate effects on the vesicular transport of [3H]glutamate thus appeared to involve mainly the DeltapH gradient rather than the potential gradient. Dithiocarbamate metabolites, the potent neurotoxin carbon disulfide included, did not affect the uptake process, thus implying the relevance for inhibition of the persistence, if any, of parent compounds in the brain. The present novel and potent in vitro interferences of selected dithiocarbamate pesticides with the vesicular transport of glutamate, if representative of in vivo alterations, may play some role in the probably complex origin of dithiocarbamate neurotoxicity.     

Safety and effectiveness of long-term interferon gamma therapy in patients with chronic granulomatous disease

In chronic granulomatous disease (CGD), diminished or absent neutrophil NADPH oxidase function leads to recurrent pyogenic infections and granuloma formation. In a recent randomized, placebo-controlled trail, short-term prophylactic use of recombinant human interferon gamma (rIFN-gamma 1b) reduced the risk of serious infection in CGD patients by 67%, The current study evaluated the safety and effectiveness of long-term rIFN-gamma therapy in CGD patients. Patients were treated three times weekly with rIFN-gamma and evaluated semiannually. Serious infections (requiring hospitalization and parenteral antibiotic therapy), adverse clinical events, and measures of growth and development were noted. Thirty patients were evaluated for 12 months. The total average duration of rIFN-gamma therapy was 2.5 years. Three patients developed a total of four serious infections (0.13 infections per patient year). This rate compare favorably with rates of 1.10 and 0.38 infections per patient year found in the placebo and rIFN-gamma groups, respectively, during a previous study. Common adverse events were fever (23%), diarrhea (13%), and flu-like illness (13%). No serious adverse event was attributable to rIFN-gamma therapy and no obvious effects on growth and development were observed. rIFN-gamma is a safe and effective adjunctive therapy for reducing the frequency and severity of serious infections in CGD patients.     

Prognostic value of hypercapnia in patients with chronic respiratory failure during long-term oxygen therapy

Hypercapnia observed in patients with chronic respiratory failure may not be an ominous sign for prognosis when they are receiving long-term oxygen therapy (LTOT). In this study, we selected 4,552 patients with chronic obstructive pulmonary disease (COPD) and 3,028 with sequelae of pulmonary tuberculosis (TBsq) receiving LTOT from 1985 to 1993 throughout Japan and prospectively analyzed their prognoses. The hypercapnic patients (PaCO2 >= 45 mm Hg) had a better prognosis than the normocapnic patients (35 <= PaCO2 < 45 mm Hg) for TBsq, but no difference was found between the two groups with COPD. Furthermore, Cox's proportional hazards model revealed that in TBsq hypercapnia was an independent factor for favorable prognosis, and that the relative risk for mortality was 0.76 in patients with 45 <= PaCO2 < 55 mm Hg, 0.64 for those with 55 <= PaCO2 < 65 mm Hg, and 0. 49 for patients with PaCO2 >= 65 mm Hg against normocapnic patients. This favorable effect of hypercapnia in TBsq was particularly apparent in the patients without severe airway obstruction. Even a rise of 5 mm Hg or more in PaCO2 over the initial 6- to 18-mo follow-up period was not associated with poor prognosis in TBsq, although it was in COPD. From these findings, we conclude that hypercapnia should not be generally considered an ominous sign for prognosis in those patients who receive LTOT.     

Coagulation system in patients with blood malignancies treated with estrogens in the course of cytostatic therapy

Hospital managers initiate a nurse orientation program modeled after critical pathways. The structure allows them to assess nurses' competency while providing experience.