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Biomedical subjects

R Friedman-Birnbaum

Publications and source records attributed to R Friedman-Birnbaum.

At least 37 records · Page 2Linked to original sources

Treatment of onychomycosis: a randomized, double-blind comparison study with topical bifonazole-urea ointment alone and in combination with short-duration oral griseofulvin.

A parallel-group double-blind study was carried out which compared the efficacy of chemical avulsion of affected nail by urea 40% and bifonazole 1% cream alone with that of the same local therapy combined with short-term oral griseofulvin in onychomycosis. A total of 120 patients were included in the study. Patients' characteristics were comparable in both treatment groups. Of the 98 patients fully evaluated, 91 had toenail involvement and only seven had fingernail involvement. Forty-six of the patients were men and 51 were women. The mean age of the patients was 47.14 +/- 13.84 years (range 17-80 years). The duration of onychomycosis was for more than 1 year in 96 patients and for 3 months duration in only one patient, who was in the placebo group. Forty patients had received different previous therapies. All topical treatments were discontinued for at least 2 weeks and oral therapy for at least 2 months prior to the beginning of the study. The diagnosis was confirmed by positive mycologic cultures. Trychophyton rubrum was identified as the pathogen in 90 patients, 45 in each group, T. tonsurans in four patients, two in each group, and T. mentagrophytes in three patients, two in the griseofulvin treated group, and one in the placebo group. The first phase of treatment given to all patients consisted of occlusive dressing every 24 h with urea 40% and bifonazole 1% ointment until the infected nail became completely detached. Subsequently, in the second phase bifonazole 1% cream was applied to the nail ped every 24 h for 4 weeks. In addition, concomitantly with the bifonazole cream the patients were randomly allocated to a daily oral double-blind treatment with griseofulvin 500 mg or placebo, for 4 weeks. Clinical and mycologic evaluations were carried out at baseline, immediately after removal of the nail, and at 3 days, 4 weeks, and 4 months after the end of treatment with bifonazole cream and griseofulvin/placebo tablets. Mycologic examination included identification of fungi by KOH preparation and culture on potato dextrose agar. Positive cultures were transfered for identification on Sabouraud's. Criteria for evaluation of efficacy comprised: "cure" defined as clinical and mycologic cure (fresh specimen and culture negative) at both investigation times after the end of treatment; "late cure" defined as mycologic cure at both investigation times after the end of treatment, clinical clearing of the nail only 4 months after the end of treatment; "improvement" defined as mycologic cure and only partial clinical improvement at both times after the end of treatment; "failure" indicating no mycologic cure (fresh specimen and/or culture positive); and "relapse" signifying a change from negative findings 1 month after the end of treatment to positive findings 4 months after the end of treatment. Adverse reactions were evaluated on each visit. Only those patients who had completed clinical and mycologic evaluation during the entire study were included in the final statistical analysis. Those patients with partial evaluation were included only in the evaluation of adverse events. Based on the assumptions of a failure rate (failure and relapse) of 30% with bifonazole cream alone and of 10% with bifonazole cream and griseofulvin tables, a = 0.05 and b = 0.2 the required sample size was at least 58 patients for each treatment group (Casagrande formula, one-sided test). The primary efficacy variable "assessment of treatment" (cure and improvement versus failure and relapse) was tested for treatment differences by Fisher's exact test (a = 0.05, one-sided test; Ho, no advantage with additional systemic therapy of griseofulvin). Additionally, the relapse rates of both treatments were tested exploratively in the same way as the primary efficacy variable. All other data were analyzed descriptively.

Administration, Oral↗

Delayed postburn blisters: an immunohistochemical and ultrastructural study.

This study was performed in an attempt to further elucidate the pathogenesis of delayed postburn blistering. Two cases were studied ultrastructurally and immunohistochemically, 1 with blisters on the recipient site of autologous split-thickness skin grafts and the other on the donor site. Ultrastructurally, the basement membrane was on the roof of the blisters in both cases, except for a single small blister in the first case where it was on the dermal floor. In the blister roofs, the basement membrane showed small or marked segments of discontinuity. In the adjacent non-blistered healed skin, the basement membrane was usually continuous, and anchoring fibrils were present. Immunoperoxidase staining on frozen sections, using antibodies to laminin, laminin 5, collagen IV, and collagen VII, showed a mostly continuous linear pattern in the adjacent non-blistered skin, which often became discontinuous near the blisters and markedly discontinuous in the blister roofs. In the blister floors, weakly stained linear or granular deposits of some of these components were sometimes also present. The results of this study support discontinuity of the basement membrane as the main anomaly in delayed postburn blistering. Disturbance in the reassembly or local breakdown of the basement membrane components might be the underlying defect.

Adult↗

Mode of c-myc protein expression in Spitz nevi, common melanocytic nevi and malignant melanomas.

The expression of c-myc protein was studied in formalin-fixed, paraffin-embedded sections of 16 compound Spitz nevi (SNs), 20 ordinary compound melanocytic nevi (MNs) and 30 malignant melanomas (MMs), using monoclonal antibody 9E10 and an immunoperoxidase technique. Nine (56%) SNs, 16 (80%) MNs and 23 (77%) MMs showed positive reactions in some of the tumor cells (P = non-significant). The staining reactions were mostly cytoplasmic, and moderate to strong in intensity. The frequencies of positively stained cells were higher in the MN and SN groups. Most of the lesions with a significant dermal component did not show stratification of staining with progressive descent into the dermis. Therefore, the mode of expression of c-myc in routinely processed specimens does not differentiate between SNs, MNs and MMs. One possible reason is that the increased expression of the c-myc protein is not sufficient alone to promote proliferation and malignant transformation in these types of tumors.

Gene Expression↗

A study of coagulation and anti-endothelial antibodies in idiopathic livedo reticularis.

Livedo reticularis is associated with collagen vascular diseases and other vaso-occlusive disorders in a substantial number of cases. In the remaining cases the cause of livedo reticularis is still unknown. (i.e., idiopathic). We sought to determine a possible causal relationship between idiopathic livedo reticularis and autoimmune factors associated with the coagulation system, including antiendothelial cell antibodies. Nine patients with idiopathic livedo reticularis were studied. All patients were found to have normal platelet count, fibrinogen levels, and prothrombin and activated partial thromboplastin times, as well as negative results for Venereal Disease Research Laboratory and D-timer tests. Anticoagulant activity was detected in 2 patients: one had positive results of thromboplastin titration index and Russell's viper venom test, as well as increased levels of anticardiolipin antibodies and anti-endothelial cell antibodies; the other has positive thromboplastin titration index, mildly increased levels of anti-endothelial cell antibodies, and markedly increased levels of antinuclear antibodies. A third patient had mildly increased levels of anti-endothelial cell antibodies alone, and a fourth patient had mildly increased levels of antinuclear antibodies only. The clinical outcome was uneventful in all of the patients during an 18-month follow-up period. These findings suggest involvement of autoimmune factors associated with the coagulation system in some patients with idiopathic livedo reticularis, whose clinical significance remains to be determined.

Adolescent↗

An immunohistochemical study of p53 protein expression in classical Kaposi's sarcoma.

The present study was performed to determine the frequency of p53 protein immunoreactivity in classical Kaposi's sarcoma (KS) as a whole and in relation to the histological subtypes which are considered to correspond to the developmental stages of the tumor. The accumulation of p53 protein was studied immunohistochemically using monoclonal antibody BP53-12 on formalin-fixed paraffin-embedded sections of 36 KS lesions, of which 14 were classified histologically as early type and 22 as spindle-cell or mixed type. No positive immunoreactivity was detected in any of the 14 early-type lesions. Among the 22 spindle-cell and mixed variants, positive staining was detected in 5-10% of the tumor cells in one lesion, 1-5% of the cells in six lesions, and in < 1% of the cells in two lesions. These very small percentages of positively stained cells in less than half of the cases of the spindle-cell and mixed variants do not support a significant role for p53 in tumor progression and evolution in KS.

Adult↗

Mucinous syringometaplasia. An immunohistochemical and ultrastructural study of a case.

Mucinous syringometaplasia (MS) is an unusual skin lesion of unknown etiology, characterized histologically by epidermal invaginations lined by mucin-laden goblet-like cells and by nonkeratinized squamous cells. The present case study was performed to elucidate further the characteristics of this lesion using immunohistochemistry and electron microscopy. The mucin-laden cells in the MS lesion stained positively for carcinoembryonic antigen, epithelial membrane antigen, and low molecular weight keratins. The ultrastructural examination, which was performed on deparaffined sections, revealed two morphological variants of mucous granules. Electron-dense mucous granules predominated in the mucus-containing cells, which were situated among the keratinocytes adjacent to the epidermal invaginations, mostly in the lower parts of the epidermis. Larger, electron-lucent granules containing flocculent material were found more abundantly in the cells lining the epidermal invaginations. Also, some of the mucus-containing cells showed bundles of tonofilaments; structures that appeared to be isolated short, stubby microvilli; and attachments to adjacent mucus-containing cells and keratinocytes by desmosomes. The ultrastructural and immunohistochemical findings in our case suggest that the mucinous changes occurred as a metaplastic process in the resident epidermal cells and were accompanied by changes in cellular antigen expression resembling those of simple secretory epithelium.

Adult↗

Normolipidemic xanthelasma palpebrarum: lipid composition, cholesterol metabolism in monocyte-derived macrophages, and plasma lipid peroxidation.

The lipid compositions of 8 normolipidemic xanthelasma palpebrarum (XP) lesions were analyzed using thin-layer chromatography, with the adjacent uninvolved skin used as control. The lesions were found to be composed predominantly of cholesterol, mostly cholesteryl ester, whereas in the control specimens phospholipids predominated. The degradation rates of 125I-low-density lipoprotein (LDL), oxidized LDL, and acetyl LDL, and the rates of intracellular cholesterol synthesis from 1,2-(14)C-acetate, in blood monocyte-derived macrophages (MDM) from 3 normolipidemic patients, were similar to those of MDM from 3 normal control subjects. The mean levels of lipid peroxides and conjugated dienes under basal conditions, as well as following the addition of a free radical-generating compound (2,2-azobis-2-amidinopropane hydrochloride) to the plasma of 14 normolipidemic XP patients were significantly higher than those of 14 age- and sex-matched normal controls. We conclude that the predominant lipid accumulated in normolipidemic XP lesions is cholesteryl ester, but there is no evidence for intrinsic cellular cholesterol metabolism derangement in blood MDM from patients which could account for this. Since macrophage cholesterol accumulation can also result from enhanced uptake of increased levels of oxidized LDL, the increased plasma lipid peroxidation (derived from oxidized LDL) might lead to accumulation of cholesterol in macrophages and formation of foam cells via this mechanism.

Adult↗

No significant association between HLA antigens and classic Kaposi sarcoma: molecular analysis of 49 Jewish patients.

Because of the abundance of the classical form of Kaposi sarcoma (CKS) among Jews and people of Mediterranean origin, studies have been conducted to find an association between CKS and HLA antigens. No conclusive results have been drawn, although in a number of these investigations an increased incidence of HLA-DR5 was reported. In our study 49 CKS patients of Jewish origin were serologically analyzed for HLA class I and class II antigens. We found no significant deviation in serologically defined HLA antigens frequencies between patients and 99 ethnically matched controls. However, a nonsignificant decrease in the frequencies of HLA-DR4, HLA-DR12, and the combination of DR4/DR11 was observed. Then we determined in these patients HLA-DRB1, HLA-DQA1, and DQB1 allelic polymorphism by oligotyping on PCR-amplified DNA. In this molecular analysis the only notable finding was a decreased frequency of the combination HLA-DQA1*0301/DQB1*0301, which appeared in one (2%) patient compared to 13 (13%) of the controls. However, the decrease was not statistically significant. On the basis of both serological and molecular analysis done on a relatively large group of CKS patients, we conclude that there is no significant linkage between HLA antigens and CKS in Jewish population.

Africa, Northern↗

Histopathologic findings in the clinically uninvolved skin of patients with mycosis fungoides.

Several of the methods of treating plaque-stage mycosis fungoides (MF) advocate treatment of the whole skin, although relatively little information exists on the histologic appearance of clinically uninvolved MF skin. Our study was performed to elucidate the histologic appearance of the clinically uninvolved skin of plaque-stage MF patients. Biopsies were taken from the clinically uninvolved skin of 18 untreated patients with plaque-stage MF, 1 cm (near) and > or = 10 cm (far) from the MF plaques, and from 23 normal, healthy controls. Eight to 12 serial sections from each specimen were examined. The most common histologic finding, which was observed in six (33%) biopsies of near skin and four (22%) biopsies of far skin compared with only one (4%) biopsy of normal control (p = 0.02 and 0.1, respectively), consisted of mononuclear-cell infiltrate around a blood vessel in the papillary dermis, with extension of some of these cells into the overlying epidermis. More diffuse and epidermotropic mononuclear cell infiltrates were seen in an additional three (17%) biopsies of near skin, whereas mild nonepidermotropic superficial perivascular or perifollicular mononuclear cell infiltrates were observed in an additional four (17%) biopsies of the normal controls. In conclusion, the most common histologic finding in our study, which was observed predominantly in the MF group, might represent an earlier stage and clinically undetectable involvement of the normal-looking skin in MF patients.

Adult↗

Immunohistochemical study of p53 protein expression in Spitz nevus as compared with other melanocytic lesions.

The accumulation of p53 protein was studied immunohistochemically on paraffin-embedded sections of 26 Spitz nevi (SNs), 26 primary invasive cutaneous malignant melanomas (MMs), 20 metastases of MM, and 17 ordinary compound nevi (CNs), using monoclonal antibody BP53-12. Positive reactivity was detected in some of the tumor cells in seven (35%) metastatic MMs, all exhibiting strong nuclear staining; eight (31%) primary MMs, of which seven showed strong nuclear staining; two (7%) SNs, of which only one showed strong nuclear staining; and none of the CNs. The frequencies of the positively stained lesions in general, and the strongly positively stained lesions in particular, in the MM and metastatic MM groups were each statistically significantly higher than the respective frequencies in the SN and CN groups. We believe that the immunohistochemical detection of p53 protein with the use of monoclonal antibodies such as BP53-12 on paraffin sections, especially when strong nuclear reactivity is demonstrated, may prove to be an adjunctive tool in the histopathologic differentiation of MM from SN.

Adolescent↗

Sun protection and sunscreen use after surgical treatment of basal cell carcinoma.

Sixty-three patients (mean age 54 +/- 9 years) who were treated for a basal cell carcinoma (BCC) and 54 control subjects (mean age 51 +/- 11 years) filled out detailed questionnaires on their sun exposure and sun protection habits. Patients were given the questionnaires at least 1 year after their skin tumors had been excised. Differences between patients and controls in mean age, gender, Fitzpatrick's skin type and eye and hair color were statistically nonsignificant. The level of education was high in both patients and controls (mean of 13.4 +/- 3.1 school years). Differences in education were statistically nonsignificant. We found that both patients and controls were knowledgeable about the role of sunscreens in preventing skin tumors (79% and 83% respectively) and in preventing sun-induced aging (90% and 85% respectively). Significantly more patients used sunscreens regularly (64%) compared with controls (36%). Nevertheless, our data show no statistically significant differences between the sun exposure habits of the patients previously treated for BCC and controls. Moreover, we found that, although 82% of the patients declared that they tried to avoid sun, only 49% regularly wore hats or shirts with long sleeves in the summer (19%). Sixty-two percent of the patients used two or fewer bottles of sunscreens per year, which is inadequate for effective year-round sun protection. In addition, we found that many patients, as well as the controls, applied sunscreens only once a day (57% and 46% respectively), did not reapply after swimming (58%, 74% respectively), and did not use sunscreens in the winter (49%, 61%). Our data show that, although patients after BCC removal have a significantly higher sunscreen use compared with controls, the amount and methods of application are less than adequate. Moreover, other simpler methods to prevent photodamage, such as simple sun avoidance or the use of protective clothing, are often neglected.

Attitude to Health↗

Localized granuloma annulare. Histopathological and direct immunofluorescence study of early lesions, and the adjacent normal-looking skin of actively spreading lesions.

We studied 10 biopsies of early (< 1 week) localized granuloma annulare (LGA) lesions and 10 specimens of the normal-looking skin adjacent to actively spreading LGA lesions for signs of vasculitis, using histological and direct immunofluorescent (DIF) techniques. In the early LGA lesions, the collagen fibers showed various forms of alterations, with hyalinization and fragmentation being the most common; in half of these lesions, neutrophils and nuclear fragments in various numbers and densities were found among the altered collagen fibers. Some of the small blood vessels in the areas of granulomatous inflammation showed endothelial cell hypertrophy in four cases, and in one case also endothelial cell proliferation and luminal occlusion. In only one case, a single small blood vessel, which was situated in the center of a palisading granuloma, showed fibrinoid necrosis of its walls. The DIF study of all 20 specimens and the histological study of the 10 specimens of normal-looking adjacent skin did not reveal immune deposits in the vessels' walls, or histological evidence of vasculitis, respectively. We believe that these findings do not support a role of vasculitis in the formation of LGA lesions, but suggest that neutrophils might play a primary or secondary role in their pathogenesis.

Fluorescent Antibody Technique↗

An unusual late reaction to Zyderm I injections: a challenge for treatment.

We describe a patient who, 2 1/2 years after injection with Zyderm I collagen, developed large erythematous indurated nodules and plaques at the facial injection sites. This occurred despite a prior negative skin test with the injectable material. Histopathologically, a sarcoid-like foreign-body reaction was present in the dermis and subcutaneous fat and muscles. Retesting with Zyderm I collagen on the forearm produced a positive reaction that showed, histologically, a sarcoid-like reaction similar to that which was found in the face. Various modes of therapy have failed to clear the facial lesions and disfigurement.

Adult↗

Enhanced low-density lipoprotein degradation and cholesterol synthesis in monocyte-derived macrophages of patients with adult xanthogranulomatosis.

Adult xanthogranulomatosis is an uncommon disorder in which dermal macrophages accumulate cholesterol intracellularly despite normal plasma cholesterol levels. In an attempt to elucidate an underlying biochemical abnormality in this disorder, we studied the rates of 125I-labeled low-density lipoprotein degradation, and intracellular cholesterol synthesis, in human monocyte-derived macrophages of three patients with adult xanthogranulomatosis. In all three patients, the rates of cellular 125I-low-density lipoprotein degradation and of cholesterol synthesis were 22-37% and 14-84% higher than those of the respective normal controls (p < 0.01). These findings suggest that in MDM of adult xanthogranulomatosis patients, the uptake and degradation of low-density lipoprotein-derived cholesterol and intracellular cholesterol biosynthesis are enhanced. Because dermal macrophages are derived from blood monocytes, it is possible that such an enhancement might play a role in the accumulation of cholesteryl esters in the macrophages that form the xanthogranulomatosis lesions.

Adult↗

Mal de Meleda keratoderma with pseudoainhum.

Pseudoainhum is an infrequent complication in the autosomal-recessive keratodermas. We describe two related families in which the diagnosis of mal de Meleda keratoderma has been confirmed by mode of inheritance and ultrastructural findings. One family member, a 9-year-old girl, developed pseudoainhum which threatened the viability of her little fingers. This responded to treatment with etretinate. The treatment dilemma posed by keratoderma-induced pseudoainhum in children, i.e. the concern over the possible skeletal toxic effects of long-term etretinate treatment vs. the risks and outcome of surgery, is discussed.

Ainhum↗

Classic and iatrogenic Kaposi's sarcoma. Histopathological patterns as related to clinical course.

The histological findings in the first diagnostic biopsy of 50 patients with Kaposi's sarcoma (KS) were classified and were related to the clinical course. Forty-one patients had the "classic KS," of whom 31 had a benign course and 10 an aggressive disease. Nine patients had iatrogenically induced KS. Histologically the following subtypes were found: mixed type in 18 patients, spindle type in 16, early type in 14, and hemangiomatous and lymphangiomatous types in one each. We did not find any statistical relationship between the histological subtypes, degree of nuclear atypia, number of mitoses, and density of the inflammatory cell infiltrates in the KS lesions, and the clinical types and course of the disease. The results of this study do not support the possibility of a prognostic importance regarding the histological features of the early lesions in patients with classic or iatrogenic Kaposi's sarcoma.

Adult↗