Recombinant human erythropoietin in the treatment of cancer-related anaemia

Abstract: The efficacy and safety of recombinant human erythropoietin (rhEPO) were tested when given subcutaneously (s.c.) in an escalating dose of 2000–10,000 units (U) daily in 60 patients with cancer-related anaemia (CRA). A positive response, defined as an increase in haemoglobin more than 2 g/dl and independence of blood transfusions, was observed in 23 of 48 evaluable patients (48%) within a median of 8 wk. In detail, rhEPO corrected anaemia in 11 of 14 patients (79%) with malignant lymphoma, in 8 of 15 patients (53%) with multiple myeloma and in 4 of 10 patients (40%) with a solid tumour. The median dose of rhEPO in successful cases was 5000 U daily. Four patients with agnogenic myeloid metaplasia and 5 with myelodysplastic disorder failed to respond to rhEPO. No patient had any severe side effects. Pretreatment serum erythropoietin levels appeared to be a weak predictor for response to rhEPO treatment. In conclusion, rhEPO seems to be safe and effective in correcting CRA in certain groups of patients.     

Effect of chronic oral domperidone therapy on gastrointestinal symptoms and gastric emptying in patients with parkinson's disease

This study investigated whether domperidone could improve gastrointestinal symptoms in patients with Parkinson's disease who were receiving levodopa therapy. A total of 11 patients were studied. Following a baseline gastric emptying test, patients were treated with a starting dose of domperidone 20 mg p.o. q.i.d. A follow-up gastric emptying test was repeated at least 4 months after starting domperidone therapy. At the beginning and at each 3-month follow-up visit, symptoms of nausea, vomiting, anorexia, abdominal bloating, heartburn, regurgitation, dysphagia, and constipation were evaluated and scored on a scale of 0–3. The overall mean follow-up period was 3 years. Compared with their baseline evaluation, patients experienced a significant improvement in all symptoms (p < 0.05) except dysphagia and constipation. Gastric emptying of an isotope-labeled solid meal was significantly faster, with a baseline result of 60.2 ± 6.4% retention of isotope 2 h after the meal compared with 37.0 ± 2.2% retention during domperidone therapy (p < 0.05). Patients' global assessment of Parkinson's disease remained stable or improved. Serum prolactin was elevated in all patients after domperidone therapy (p < 0.05). Domperidone therapy significantly reduces upper gastrointestinal symptoms and accelerates gastric emptying of a solid meal, but does not interfere with response to antiparkinsonism treatment.     

Periodontal status of a subject sample of Yemen

Abstract From August to October 1991, the periodontal status of 1001 Yemenis representing the age groups 12-14, 15-19, 20-24 and 35-44 years was recorded and evaluated with preference to the CPITN, the calculus index and clinical attachment levels. The impact of chewing khat, the leaves of a cultivated, alkaloid shrub, and of using the traditional miswak chewing stick for oral hygiene purposes were investigated. The results show that 6.9% of the juvenile probands (15-19 years) had healthy periodontal tissue (CPITN 0). whereas bleeding on probing and calculus (CPITN 1+2) were registered in 86.2%. In the 35-44 year age group. 1.7% were periodontally healthy, whereas 84.5% displayed plaque retention or shallow pocketing (CPITN 2-3) and 12.5% deep pocketing (CPITN 4). The treatment needs in all age groups are confined primarily to calculus removal and instruction in oral hygiene. The clinical attachment level and the calculus index revealed age-related attachment loss and calculus formation, primarily among male probands. The higher khat consumption among the male population is reflected in its detrimental effect on the periodontal tissue, especially among younger probands. Oral hygiene aids have also an influence on periodontal status, with a toothbrush proving more efficient than the miswak. WHO efforts directed towards prophylactic programs need to be intensified but can be staffed by dental hygienists.     

A newly recognized point mutation in the cytochrome b558 heavy chain gene replacing alanine57 by glutamic acid,in a patient with cytochrome b positive X-linked chronic granulomatous disease

Molecular genetic analysis was performed in a patient with cytochrome b positive X-linked chronic granulomatous disease. A previous Southern blot study, using a cytochrome b heavy chain cDNA as probe, revealed a Pst I restriction fragment pattern for the cytochrome b heavy chain gene (CYBB) different to that of normal individuals. Since restriction length polymorphism with Pst I has never been observed in control individuals and no abnormal restriction fragment patterns in the patient's CYBB was detected with seven other enzymes used, we focussed on the single Pst I site in the CYBB cDNA as being the only mutation site responsible for his disease. A fragment of the patient's cDNA which included the Pst I site was amplified by reverse polymerase chain reaction, and loss of the Pst I site in the fragment was confirmed by incubation with Pst I. Subsequent sequence analysis of the fragment revealed a point mutation in the Pst I site (cytosine to adenine), substituting glutamic acid for alanine at position 57.     

The management of Darier's disease

Darier's disease (keratosis follicularis) is a rare, dominantly inherited condition which is characterised by the presence of warty papules and plaques on the trunk, scalp and flexures. Diagnostic nail changes are present in most patients. Suprabasal clefting, acantholysis and dyskeratosis are present in involved skin and the diagnosis may be confirmed by a skin biopsy. The disease never remits. Exacerbating factors such as heat, sweating and ultraviolet light should be avoided. Topical therapy with emollients, moderately potent corticosteroids and antimicrobials may provide some symptomatic relief, but have no effect on the progress of the disease. Oral retinoids are effective in most patients. Complications such as cutaneous infections, blistering and salivary gland obstruction may occur in some patients.     

Lymphangiosarcoma in late-onset hereditary lymphedema: Case report and nosological implications

Hereditary lymphedemas that are not associated with other malformations usually affect the lower limbs and are inherited in an autosomal dominant fashion. These non-syndromic hereditary lymphedemas are categorized by their age of onset, being either congenital (Milroy disease) or having an onset in childhood or around puberty (Meige disease). We describe a family in which three individuals in three generations had unusually late onset of lym-phedema in their mid-twenties or thirties. The proband additionally developed a very rare lymphangiosarcoma. This tumor, usually associated with post-mastectomy lym-phedema, has not been described in late-onset hereditary lymphedema. Because of an unusually high incidence of multiple primary tumors in association with lymphangiosarcoma in the literature (approximately 10%) and the proband's own familial cancer background, we speculate that an inherited predisposition to malignancy may underlie the development of lymphedema-associated lymphangiosarcoma. © 1995 Wiley-Liss, Inc.     

Back pain from the epidemiological point of view

Summary In the last decades back pain has reached dramatic proportions in industrialized countries. Disorders of the back are nowadays the leading cause of direct and indirect health care costs. Accurate prevalence estimates are needed to serve as a basis for health care evaluations. A review of epidemiologic studies in the general population reveals that back pain has reached a prevalence of 40 % for current pain. 7 to 18 % are “frequently”, “often”, “daily” or “constantly” affected. 75 % of the adult population suffers from back pain during the last year. 80 to 90 % of the adult population in industrialized countries experience back pain ever. Gender specific differences are only present in severe, chronic forms which are more often experienced by women. Back pain has a prevalence maximum at 50 to 64 years. Older persons display lower prevalence estimates. The prevalence maximum in men is one decade earlier than in women. There are several potential explanations for this prevalence pattern that are discussed in the article. Back pain can be classified by location, temporal characteristics, pain intensity and pain history. Currently, for none of these dimensions generally accepted, uniformly employed and validated definitions are available. In most of the industrialized countries back pain is one of the most expensive symptoms. 75–90 % of the direct and indirect health care costs were caused by those 5–10 % of patients who are disabled. As predictors of back pain a history of back pain and job satisfaction play by far a more important role than the extensively studied mechanical factors. For a first episode of back pain the prognosis is favorable. If the pain persist for more than three months the prognosis is unfavorable. After six months of absenteeism because of back pain more than half of the afflicted never return to work. Rarely back pain is present as a single symptom. In more than 80 % back pain is associated with pain in at least one joint. It remains to be studied if back pain may be viewed as an entity or as part of a more complex pain syndrome.      

The mitogenic effect of KGF and the expression of its cell surface receptor on cultured normal and malignant human oral keratinocytes and on contiguous fibroblasts

This study examined the mitogenic response to keratinocyte growth factor (KGF) of normal and tumour-derived human oral keratinocytes in which the degree of cellular differentiation was known and in contiguous fibroblast cultures derived from the malignant epithelial cultures. Keratinocytes, but not fibroblasts, were stimulated by KGF. There by demonstrating epithelial target cell specificity of the ligand. KGF-induced stimulation of the tumour-derived keratinocytes cultured in the absence of the 3T3 fibroblast support broadly correlated with the degree of cellular differentiation; well-differentiated keratinocytes were stimulated more by KGF than their less differentiated counterparts. Malignant oral keratinocytes expressed KGF cell surface receptors (K_D 451-709 pM; receptors/cell 2306-413645), but KGF receptor mRNA did not correlate with either KGF-induced mitogenesis or the degree of epithelial cell differentiation. When the tumour-derived keratinocytes were cultured in the presence of 3T3 fibroblasts, the mitogenic response to KGF was comparable to normal epithelial cells. The results suggest that KGF-mediated growth stimulation may not be significant in providing a selective advantage for the growth of malignant keratinocytes.     

Case-control study of the alpha-synuclein interacting protein gene and Parkinson's disease.

We conducted a case-control study of the alpha-synuclein-interacting protein gene (SNCAIP, also known as synphilin-1) and Parkinson's disease (PD). A total of 319 PD cases and 195 controls were genotyped for four SNCAIP variants, including a microsatellite repeat in intron 4 and three restriction fragment length polymorphisms (RFLP) proximal to the 5' terminal of exons 1, 4, and 6. None of the variants were found associated with PD overall. Global score statistics were not significant for four, three, and two loci haplotypes. All four loci were in linkage disequilibrium for cases, controls, or both groups combined (P < 0.0001). Recursive partitioning showed no interactions between variants of the SNCAIP gene and variants of the alpha-synuclein gene (SNCA) or the parkin (PARK2) gene.     

Restless legs syndrome in Parkinson's disease: a case-controlled study.

Restless legs syndrome (RLS) is a disorder of motor activity with a circadian pattern, occurring frequently in patients with Parkinson's disease (PD). We sought to estimate the prevalence of RLS in Indian PD patients. One hundred twenty-six consecutive PD patients and 128 healthy age- and sex-matched controls were evaluated using a predesigned questionnaire. RLS was present in 10 of 126 cases of PD (7.9%) and 1 of 128 controls (0.8%, P = 0.01). PD patients with RLS were older than those without RLS (63.70 +/- 7.80 years vs. 57.37 +/- 10.04 years; P = 0.05) and had higher prevalence of depression (40% vs. 10.3%; P = 0.023). No demographic factors or factors related to PD correlated with the presence or severity of RLS. RLS is more common among patients with PD than controls. A greater medical recognition of this disorder is needed in view of available effective treatment.