Clinically significant drug interactions in dermatology

Several glycoproteins that are present at the nuclear rim and at the nuclear pore complex of tobacco suspension-cultured cells are modified by O-linked oligosaccharides with terminal N-acetylglucosamine (GlcNAc). Here, we report on the purification of several of these glycoproteins, which are referred to as terminal GlcNAc (tGlcNAc) proteins. In vitro galactosylation of the tGlcNAc proteins generated glycoproteins with terminal galactosyl-beta-1, 4-GlcNAc and thus permitted their isolation by Erythrina crystagalli agglutinin affinity chromatography. Peptide sequence information derived from one tGlcNAc protein with an apparent molecular mass of 40 to 43 kD, designated gp40, made it possible to clone its gene. Interestingly, gp40 has 28 to 34% amino acid identity to aldose-1-epimerases from bacteria, and no gene encoding an aldose-1-epimerase has been isolated previously from higher organisms. Polyclonal antibodies were generated against recombinant gp40. Consistent with its purification as a putative nuclear pore complex protein, gp40 was localized to the nuclear rim, as shown by biochemical fractionation and immunofluorescence microscopy.     

Clinically significant drug interactions in HIV-infected patients

In recent years the availability of highly active antiretroviral therapies and prophylaxis and treatment of opportunistic infections in patients with HIV-disease have reduced morbidity and mortality. Many different drugs may be prescribed in a patient simultaneously. Therefore, the potential for interactions between different substances is increased. The possible mechanisms of drug interaction concern pharmakokinetics (absorption, metabolism, elimination) and pharmakodynamics. They can lead to significant changes in plasma concentrations and may affect efficacy and toxicity of a drug. One of the most important mechanisms of interaction is the inhibition or induction of the hepatic cytochrome P-450 enzyme system. All protease-inhibitors are metabolized by CYP450, mostly by the subunit 3A4. Proteinase-inhibitors are themselves very potent inhibitors of CYP4503A4 and increase the concentration of drugs metabolized this way. This article summarises the most important mechanisms of drug interactions and demonstrates the most frequent and clinical significant consequences.     

Clinically significant, isolated metastatic disease to the thyroid gland

Despite being second only to the adrenal glands in terms of relative vascular perfusion, the thyroid gland is a rare site of metastatic disease; but when thyroid metastases occur, long-term survival has been reported to be dismal. To determine the incidence and management of isolated, metastatic disease to the thyroid, we reviewed our clinical experience. Between June 1986 and August 1994 ten patients underwent thyroidectomy for isolated, metastatic disease of nonthyroidal origin (mean +/- SD age 58 +/- 6 years, 30% female). The primary tumors were renal cell carcinomas (RCCs) (n = 5), esophageal adenocarcinoma (n = 1), pulmonary squamous cell carcinoma (n = 1), gastric leiomyosarcoma (n = 1), lingual squamous cell carcinoma (n = 1), and parotid gland carcinoma (n = 1). Three patients underwent preoperative fine-needle aspiration (FNA), all of which were suggestive of metastatic disease. The mean time from resection of the primary tumor to thyroid metastases was 3.5 +/- 6.0 years (range 0-19.5 years). Total thyroidectomy (n = 5) or lobectomy (n = 5) was performed without morbidity or mortality. After a median follow-up of 5.2 years six patients are alive and two are free of disease. Moreover, no patients have had recurrent disease in the neck. Thus carcinomas metastatic to the thyroid represent a rare cause of clinically significant thyroid disease, with RCCs comprising 50%. Most thyroid metastases (80%) present within 3 years of primary tumor resection, but with RCC they can occur as late as 19 years. The diagnosis of metastatic disease should be suspected in patients with even a remote history of cancer, especially RCC, and an FNA revealing clear cell or spindle cell carcinoma. Contrary to previous reports, long-term survival can be achieved after resection of the metastatic tumor. Furthermore, thyroidectomy may also palliate/prevent the potential morbidity of tumor recurrence in the neck.     

Clinically significant change: Jacobson and Truax (1991) revisited.

The relationship between statistically and clinically significant change has been enigmatic. N. S. Jacobson and P. Truax (1991) have proposed an important step toward rapprochement. However, their suggested index of clinically significant change neglects possible confounding of improvement rate estimates by regression to the mean. An alternative method is described that incorporates an adjustment that minimizes this confounding when statistical regression has been shown to be present. If regression is not present, the Jacobson and Truax method is more appropriate; if regression is present, the Edwards-Nunnally method (D. W. Edwards et al, 1978) is more appropriate. The 2 methods are compared, and the effects of instrument reliability and sample deviance on estimated improvement rates are demonstrated using general well-being test–retest data from a sample of older adult mental health outpatients. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Clinically significant hearing loss in renal allograft recipients treated with intravenous erythromycin

BACKGROUND: Hearing loss is generally regarded as a rare side effect of erythromycin therapy. However, our own clinical experiences in erythromycin-treated patients led us to suspect that this complication may be more common among renal allograft recipients. The purpose of this study was to evaluate the incidence, predisposing factors, clinical characteristics, and outcomes of erythromycin-induced hearing loss among renal allograft recipients. METHODS: We reviewed medical records of renal transplant patients treated for pneumonia with intravenous erythromycin lactobionate. Patients were evaluated for the occurrence of clinically significant hearing loss (including onset, duration, and reversibility), other signs and symptoms of ototoxicity (vertigo and tinnitus), daily erythromycin dose and duration of treatment, concurrent ototoxic drug therapy, renal and hepatic function, and history of previous otic disease. RESULTS: Eleven (32%) of 34 courses of intravenous erythromycin therapy resulted in hearing loss. The incidence of hearing loss was 53% (eight of 15 courses) in patients treated with 4 g of erythromycin daily compared with 16% (three of 19 courses) among those receiving 2 g/d (P = .05). In addition, courses of erythromycin were longer in those suffering auditory toxicity (9.6 +/- 4.7 days) than in nontoxic patients (5.7 +/- 3.6 days) (P < .05). Hepatic and renal function did not differ between toxic and nontoxic patients. All episodes of erythromycin-induced hearing loss were reversible. CONCLUSIONS: We conclude that clinically significant hearing loss occurs in more than 30% of renal allograft recipients treated for pneumonia with intravenous erythromycin lactobionate. Patients who require prolonged courses of erythromycin and those treated with 4 g/d are at particular risk for the development of auditory toxicity. With prompt recognition and modification of therapy, erythromycin-induced hearing loss appears to be completely reversible.     

Clinically significant azole cross-resistance in Candida isolates from HIV-positive patients with oral candidosis

OBJECTIVES: To determine the proportion of fluconazole-resistant Candida albicans isolates that have clinically significant cross-resistance to itraconazole or ketoconazole, that is sufficient to result in failure of these agents at their standard doses (200 and 400 mg daily for 7 days, respectively). METHODS: Seven hundred C. albicans isolates from HIV-positive patients with oral candidosis underwent susceptibility testing using a relative growth method, for which cut-off values corresponding to clinical drug failure have been established. RESULTS: A total of 431 isolates were fully azole-susceptible and three main resistance patterns were detected: isolates resistant to fluconazole alone (n = 100); isolates resistant to fluconazole and ketoconazole but susceptible to itraconazole (n = 94); and isolates resistant to all three drugs (n = 50). No isolates were consistently resistant to ketoconazole without being fluconazole-resistant, and no itraconazole resistance was detected without ketoconazole resistance. Resistance to fluconazole alone was more common in specimens obtained soon after first clinical fluconazole failure, whereas specimens from patients with a longer history of fluconazole-unresponsive candidosis were more likely to be infected with cross-resistant isolates. Median days of prior azole exposure and cumulative fluconazole dose were significantly less for those with isolates resistant to fluconazole alone than for those with ketoconazole cross-resistant isolates, who had received less azole therapy and smaller cumulative fluconazole doses than those with isolates cross-resistant to all three drugs (although not statistically significant). After the diagnosis of fluconazole-unresponsive candidosis, increasing cumulative doses of itraconazole solution were associated with increasing likelihood of cross-resistance. CONCLUSIONS: Clinically significant cross-resistance to other azoles may occur in fluconazole-resistant isolates of C. albicans, although initially most isolates are not cross-resistant and the detection of cross-resistant isolates is associated with a history of greater prior azole exposure. Patients who have been treated for fluconazole-resistant candidosis for longer and with greater cumulative doses of itraconazole solution tend to become infected with increasingly cross-resistant isolates of C. albicans.     

"Clinically significant change: Jacobson and Truax (1991) revisited": Correction.

Reports an error in the original article by D. C. Speer (Journal of Consulting & Clinical Psychology, 1992[Jun], Vol 60[3], 402–408). On page 402, column 2, line 3, the symbol for standard deviation was omitted. The correct formula is SE?=?SD[1?–?rxx]1/2. (The following abstract of this article originally appeared in record 1992-29860-001.) The relationship between statistically and clinically significant change has been enigmatic. N. S. Jacobson and P. Truax (1991) have proposed an important step toward rapprochement. However, their suggested index of clinically significant change neglects possible confounding of improvement rate estimates by regression to the mean. An alternative method is described that incorporates an adjustment that minimizes this confounding when statistical regression has been shown to be present. If regression is not present, the Jacobson and Truax method is more appropriate; if regression is present, the Edwards-Nunnally method (D. W. Edwards et al, 1978) is more appropriate. The 2 methods are compared, and the effects of instrument reliability and sample deviance on estimated improvement rates are demonstrated using general well-being test–retest data from a sample of older adult mental health outpatients. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Clinically significant behavior problems during the initial 18 months following early childhood traumatic brain injury.

Objective: This study looked at the emergence of clinically significant problems in behavior, executive function skills, and social competence during the initial 18 months following traumatic brain injury (TBI) in young children relative to a cohort of children with orthopedic injuries (OI) and the environmental factors that predict difficulties postinjury. Participants: Children, ages 3–7 years, hospitalized for severe TBI, moderate TBI, or OI were seen shortly after their injury (M = 40 days) and again 6 months, 12 months, and 18 months postinjury. Design: Behavioral parent self-reports, demographic data, family functioning reports, and home environment reports were collected at injury baseline and each time point postinjury. Results: Results suggest that, compared with the OI group, the severe TBI group developed significantly more externalizing behavior problems and executive function problems following injury that persisted through the 18-month follow-up. Minimal social competence difficulties appeared at the 18-month follow-up, suggesting a possible pattern of emerging deficits rather than a recovery over time. Conclusions: Predictors of the emergence of clinically significant problems included permissive parenting, family dysfunction, and low socioeconomic status. The findings are similar to those found in school-age children. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Some significant differences and more significant similarities.

Continues the interchange between J. Wolpe (see record 1985-26136-001) and A. A. Lazarus (see record 1986-15103-001) on the efficacy of behavior therapy (BT) in the treatment of neurosis. In addition to responding to specific criticisms by Wolpe, Lazarus notes that the overall trajectories and objectives of both BT and multimodal therapy (which has behavioral aspects) are closely allied. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Association between incidence of Aspergillus antigenemia and exposure to construction works at a hospital site

During the course of extensive building activity in the vicinity of bone marrow transplantation wards, the patients were routinely screened for the occurrence of Aspergillus galactomannan antigen in serum. In 19 (6.7%) out of 285 patients, an antigenemia was detected. Eleven (58%) of the 19 antigenemic patients suffered from autopsy-proven or clinically suspected invasive aspergillosis. The yearly incidence of antigenemic patients differed significantly, ranging from 0% in the year without building activities to 20.9% in the year with major activities, particularly interior completion works and landscaping. It is concluded that Aspergillus antigen monitoring of bone marrow transplant recipients has a limited value for the diagnosis of manifest invasive aspergillosis. However, it it epidemiologically useful to assess the extent of intensive contact with aspergilli and to control the effectivity of preventive measures.     

A significant stride toward the comparative study of control.

Comments on the discussion by J. R. Weisz et al (see record 1985-19980-001) of the distinction between the primary form of control, which is characteristic of Americans and emphasizes influence over existing reality, and the secondary form of control, which is characteristic of Japanese and emphasizes accommodation. The present author discusses forms of control in Japan in relation to the methods of control used, the context boundedness of interpersonal relations, and the concept of the self. (3 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

A population-based incidence study of chronic fatigue

BACKGROUND: Although isoflurane may cause subendocardial hypoperfusion in the presence of coronary stenosis because of its coronary arteriolar dilatory effects, it is not known how the subendocardial microcirculation is affected. The authors examined the effects of isoflurane on poststenotic subendocardial microvessels with coronary stenosis. METHODS: The authors observed subendocardial microvessels in in situ beating swine hearts with or without critical stenosis of the left anterior descending coronary artery (LAD) with a needle-type videomicroscope during isoflurane- (ISO-H), adenosine- (ADE-H), and nitroglycerin- (NTG-H) induced hypotension (mean arterial pressure, 55 mmHg). Regional myocardial function, oxygen balance, and lactate metabolism in the region perfused by the LAD also were determined. RESULTS: In swine with stenosis, there were no differences in heart rate, cardiac output, and LAD blood flow among the three types of hypotension. Regional lactate production and anterior interventricular venous pO2 were similar during ISO-H and NTG-H but higher during ADE-H. With videomicroscopy, about half as many subendocardial microvessels could be visualized during ADE-H as with ISO-H and NTG-H. The average decrease in the systolic diameter of subendocardial microvessels of greater than 100 microm was 9 +/- 6% during ISO-H and 12 +/- 5% during NTG-H, but no consistent phasic diameter changes were observed during ADE-H. In swine without stenosis, a systolic diameter decrease was observed during all three types of hypotension. CONCLUSIONS: These findings suggest that hypotension induced by isoflurane or nitroglycerin preserves phasic diameter changes in subendocardial microvessels in the presence of critical coronary stenosis, whereas that induced by adenosine does not.     

A preliminary study on dressing patterns and incidence of candidiasis

The incidence of candidiasis in two groups of voluntary participants wearing tight and loose fitted dresses was investigated by both microscopic and cultural techniques for a period of two months. Two-thirds of the positives by stain and culture were recovered from those wearing tight clothing (P < 0.05). The findings suggest that tight clothing can predispose the wearer to candidiasis, an organism that can cause vaginitis. (Am J Public Health 1982; 72:176-177.)     

Necrotizing crescentic glomerulonephritis without significant immune deposits: a clinical and serological study

To determine the spectrum of systemic diseases associated with pauci-immune necrotizing crescentic glomerulonephritis, we have analysed extra-renal manifestations, occurrence of extra-glomerular vasculitis and incidence and specificity of antinuclear cytoplasmic antibodies (ANCA) in 40 patients selected only on renal histological criteria. Extra-renal symptoms were unexpectedly observed in all patients but one, and were suggestive of vasculitis in 24. Extra-glomerular vasculitis was seen in 18 kidney biopsies and four biopsies from other organs. Among the 33 patients with suspected or established vasculitis, 13 had presumed or biopsy-proven Wegener's granulomatosis, three had a macroscopic form of polyarteritis nodosa and 17 could not be adequately classified. An additional patient had clinical signs of Wegener's granulomatosis without clinical and histological evidence of vasculitis. ANCAs were detected in 28 of 33 and 25 of 34 sera tested by immunofluorescence and enzyme-linked immunoassay, respectively: 19 contained anti-myeloperoxidase antibodies and six had anti-proteinase 3 activity. Anti-myeloperoxidase and anti-proteinase 3 antibodies were present in all clinical subgroups but with various frequencies: anti-myeloperoxidase antibodies were more common (six of 12) than anti-proteinase 3 (four of 12) in patients with suspected or histologically proven Wegener's granulomatosis. Anti-proteinase 3 antibodies were 3- to 4-fold more common in patients with Wegener's granulomatosis than in those with systemic vasculitis of other causes (one of 12) or necrotizing crescentic glomerulonephritis without evidence of extra-renal vasculitis (one of 10). These results strongly suggest that pauci-immune necrotizing crescentic glomerulonephritis belongs to the broad spectrum of necrotizing vasculitides affecting glomerular capillaries. This study shows substantial improvement in renal prognosis and life expectancy with aggressive immunosuppressive therapy despite the older age of the patients, dissemination of the vasculitic process and often delayed diagnosis.     

Renal study protocol with ultrasonography: biometry and incidence of disease

The present study establishes the size of the kidneys in adult males and females according to three age groups, under 30, 30 to 60, and over 60, in our community. To this end, morphologically normal kidneys were studied, considering four diameters: longitudinal (L), antero-posterior (AP), transverse (T) and cortical (D). We found that renal size, in all diameters, was larger in males and females, and the left one larger than the right one. The study include 522 kidneys, from a total of 247 subjects. Apart from renal biometry, the incidence of disease was also recorded. Ten different possibilities were included in the picture: 1) Normal (N); 2) Cysts (C); 3) Lithiasis (L); 4) Tumour (T); 5) Pyelonephritis (PN); 6) Acute Focal Nephritis (AFN); 7) Hydronephrosis (HN): 8) Double Excretory System (DES): 9) Abscesses (A); and 10) ther (O). The incidence of disease is maximal in subjects over 60, with predominance of women and left kidney; most frequent changes were cysts and pyelonephritis. Of the three age groups, those under 30 had a mean age of 22.36 years, 85% being between 18 and 30 years; in the intermediate group, 30 to 60 years, mean age was 48.40 with 65% between 45 and 60; in the over 60 group, mean age was 68.67 with 70% between 61 and 70 years of age.     

Marital status and schizophrenia: A study of incidence and outcome.

Investigated the relationships between marital status and the incidence and prognosis of schizophrenia, based on a considerably more representative sample (N = 213) than previously available. Results provide strong evidence that the rate differentials and differences in outcome so often observed for marital status categories do not derive from inadequate or inappropriate sampling or statistical manipulation. In additional analyses, controlling for differential social class and severity of pathology, however, the relationships with prognosis could no longer be observed. These latter findings suggest that a process of selection by marriage is the more tenable interpretation of the relationships under consideration. (15 ref.) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Rolandic epilepsy: an incidence study in Iceland

PURPOSE: We wished to determine incidence, clinical features, and prognosis of benign rolandic seizures (BRS) and benign rolandic epilepsy (BRE) in a total population. METHODS: Cases were ascertained through review of all EEG records, and diagnosis was verified by review of medical records. Follow-up information regarding seizures and treatment was obtained from parents and treating physicians. RESULTS: In the Icelandic population aged 3-15 years, the incidence of BRS is 6.2 and BRE 4.7 in 100,000. Five years after onset 95% were seizure-free. At last follow-up, all were seizure free and had not been treated with antiepileptic drugs (AEDs) for at least 1 year. CONCLUSIONS: Our study demonstrates that BRS is a common entity in children. The prognosis is excellent and treatment is not necessary in all cases. It is important to identify BRE/BRS correctly and distinguish it from other types of epilepsy.     

Cohort study of serum total cholesterol and in-hospital incidence of infectious diseases

A multiethnic cohort of adult members of the Kaiser Permanente Medical Care Program (55300 men and 65271 women) was followed for 15 years (1979-93) to assess the association between total cholesterol and risk of infections (other than respiratory and HIV) diagnosed in the in-patient setting. Using multivariate Cox regression, total cholesterol was inversely and significantly related to urinary tract, venereal, musculo-skeletal, and all infections among men; and to urinary tract, all genito-urinary, septicaemia or bacteraemia, miscellaneous viral site unspecified, and all infections among women. The reduction of risk of all infections associated with a 1 S.D. increase in total cholesterol was 8% in both men (95% CI, 4-12 %) and women (95% CI, 5-11%). For urinary tract infections among men, as for septicaemia or bacteraemia and nervous system infections among women, the risk relation was restricted to persons aged 55-89 years. Nervous system infections were positively related to total cholesterol among women aged 25-54. In both genders, the significant inverse association with all infections persisted after excluding the first 5 years of follow-up. Collectively, these data are suggestive of an inverse association, although not entirely consistent, between total cholesterol and incidence of infections either requiring hospitalization or acquired in the hospital. Further research is needed to elucidate whether these associations are biologically plausible or represent uncontrolled confounding by unmeasured risk factors.     

Tuberculosis incidence in Northern Ireland and the Republic of Ireland--a collaborative study

The present Animal Protection Act (APA) provides two options for the seizure of animals because of welfare reasons. The seizure of animals based on section 16 a, sentence 2, no. 2 APA is only possible if the later redelivery to the owner is intended. The definitive seizure can be based on section 19 APA when a criminal or disciplinary procedure is carried out. The general statutes of preventing danger in the federal states are not applicable.     

Improved posterobasal segment function after thrombolysis is associated with decreased incidence of significant mitral regurgitation in a first inferior myocardial infarction

OBJECTIVES: This study was designed to investigate the association between wall motion abnormalities and the occurrence of ischemic mitral regurgitation in patients with a first inferior or posterior myocardial infarction and to reassess the role of thrombolytic treatment in these patients. BACKGROUND: We previously demonstrated that thrombolytic therapy reduces the incidence of significant mitral regurgitation in patients with a first inferior myocardial infarction, but the mechanisms responsible for this decrease were not clear. METHODS: Wall motion score on two-dimensional echocardiography (16 segments) and mitral regurgitation grade (0 to 3) on Doppler color flow imaging were assessed in 95 patients (in 47 after thrombolysis) at 24 h, 7 to 10 days and 1 month after myocardial infarction. Significant mitral regurgitation was defined as moderate or severe (grade 2 or 3). RESULTS: Multivariate analysis revealed that the presence of an advanced wall motion abnormality of the posterobasal segment of the left ventricle was the most significant independent variable associated with significant mitral regurgitation: odds ratio (OR) 15.0, 90% confidence interval (CI) 1.4 to 165.6 at 24 h; OR 2.8, CI 0.9 to 9.3 at 7 to 10 days; OR 4.2, CI 1.2 to 11.4 at 1 month. Thrombolysis reduced the prevalence of advanced wall motion abnormalities in the posterobasal segment at 24 h (55% vs. 75%, OR 0.5, CI 0.2 to 0.99), 7 to 10 days (44% vs. 73%, OR 0.3, CI 0.1 to 0.7) and 1 month (36% vs. 56%, OR 0.4, CI 0.2 to 0.9). CONCLUSIONS: There is a strong association between advanced wall motion abnormalities in the posterobasal segment and significant mitral regurgitation. In this study group, thrombolysis reduced the prevalence of advanced wall motion abnormalities in the posterobasal segment and thereby reduced the incidence of significant mitral regurgitation.