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HLA-A, -B, -DRB1, -DQA1, and DQB1 alleles were studied in Iberian and Algerian populations by serology and DNA sequence methodologies. The genetic and cultural relatedness among Basques, Spaniards, and paleo-North Africans (Berbers or Tamazights) was established. Portuguese people have also maintained a certain degree of cultural and ethnic-specific characteristics since ancient times. The results of the present HLA study in Portuguese populations show that they have features in common with Basques and Spaniards from Madrid: a high frequency of the HLA-haplotypes A29-B44-DR7 (ancient western Europeans), A2-B7-DR15 (ancient Europeans and paleo-North Africans), and A1-B8-DR3 (Europeans) are found as common characteristics. Portuguese and Basques do not show the Mediterranean A33-B14-DR1 haplotype, suggesting a lower admixture with Mediterraneans; Spaniards and Algerians do have this haplotype in a relatively high frequency, indicating a more extensive Mediterranean genetic influence. The paleo-North African haplotype A30-B18-DR3 present in Basques, Algerians, and Spaniards is not found in Portuguese either. The Portuguese have a characteristic unique among world populations: a high frequency of HLA-A25-B18-DR15 and A26-B38-DR13, which may reflect a still detectable founder effect coming from ancient Portuguese, i.e., oestrimnios and conios; Basques and Algerians also show specific haplotypes, A11-B27-DR1 and A2-B35-DR11, respectively, probably showing a relatively lower degree of admixture. A neighbor-joining dendrogram place Basques, Portuguese, Spaniards, and Algerians closer to each other and more separated from other populations. Genetic, cultural, geological, and linguistic evidence also supports the hypothesis that people coming from a fertile Saharan area emigrated towards the north (southern Europe, Mesopotamia, the Mediterranean Islands, and the North African coast) when the climate changed drastically to hotter and drier ca 10 000 years B.C.

HLA-B is the most polymorphic of the major histocompatibility complex classical class I loci. This polymorphism is mainly in exons 2 and 3, which code for the molecule's alpha 1 and alpha 2 domains and include the antigenic peptide binding site. Recent studies have indicated that not only exons but also the intron 2 region may be involved in the generation of certain HLA-B alleles such as B*3906 and B*1522. To study the degree of intron 2 participation and the mechanisms that generate polymorphism at the HLA-B locus, intron 1 and 2 sequences from the HLA-B35, -B5, -B16 and -B15 groups of alleles were obtained. A group-specific intronic polymorphism was found: namely, B*5301 shows intron 1 and 2 sequences identical to those found in all B35 alleles studied. On the other hand, B*5101 and B*52012 show the same intron 1 and 2 sequences and their intron 1 is the same as that found in the B35 group. This suggests that B5 and B35 groups of alleles may have arisen from a common ancestor. All known B16 alleles show the same introns 1 and 2, with the exception of B*39061 and B*39062, and all B15 alleles also bear the same introns 1 and 2, with the exception of B*1522. Variability at intron 1 is more restricted than at intron 2, and the use of intron 1 for HLA-B allele phylogenetic analysis is better for grouping alleles of a postulated common origin. In conclusion, there is a remarkable conservation of intronic sequences within related HLA-B alleles, which probably reflects a common origin and perhaps a selective force avoiding DNA changes. Intronic sequences are also potentially useful to design DNA typing strategies.

Current registries provide information only on the number of diabetic patients with end-stage renal failure, more detailed information on the incidence of diabetic nephropathy with incipient renal failure is currently not available. The Nephrology Service of Hospital Infanta Cristina in Badajoz serves a population of approximately 650,000. In the time span between 1.1.90 and 31.12.94 the outpatient clinic and the renal ward had 1,717 admissions for evaluation of renal illness, 166 due to diabetic nephropathy (9.7% of total. Twelve (7.2%) were type I diabetics (mean age, 29.9 +/- 6.2 years), and 154 were type II diabetics (mean age 63.4 +/- 9.8 years). The annual incidence increased from 41.5/mio in 1990 to 61.5/mio in 1994. In parallel, 286 patients were admitted for renal replacement therapy, i.e. 88/mio/year. Of this group 60 patients had diabetes: type I, 8 patients (13.3%, mean age 3.7 +/- 6.4); type II, 52 patients (86.7%, mean age 66.0 +/- 6.6 years). This corresponds to an admission rate for dialysis of 18.5/mio/year (19.6% of all patients), with a increasing incidence rate from 13.8/mio in 1990 to 23.1/mio in 1994. This incidence of diabetic nephropathy is more than two-fold greater than the previously reported incidence by the EDTA registry for Spain, it is six-fold greater that the figure recorded for our region. Although the rates of incidence and prevalence of renal failure due to diabetic nephropathy founded in this study seems still to be lower than those of other developed european countries, it is detected a trend toward an increase of these figures in the latter years.

Expression of Na(+)-K(+)-adenosinetriphosphatase (ATPase) in tissues from obese and lean Zucker rats was monitored. The phosphatase activity of the sodium pump was increased in liver and intestinal mucosa from obese animals but was unaltered in skeletal muscle, brown adipose tissue, kidney, and heart. Induction of Na(+)-K(+)-ATPase activity was correlated with increased alpha 1-subunit protein amounts in liver and intestinal mucosa, although alpha 1-subunit mRNA levels were increased only in liver tissue. Neither protein nor mRNA amounts for both subunits were significantly altered in the other tissues analyzed. The only exception was a decrease in the amount of beta 1-protein in kidney from obese rats. alpha 2-Subunit protein and alpha 2- and beta 2-mRNA levels were not altered in brown adipose tissue, heart, and soleus. In summary, this study shows that in obese Zucker rats the expression of the sodium pump is enhanced in tissues that are directly involved in nutrient uptake and processing. This adaptation may be related to the ongoing hyperphagia and to tissue hypertrophia but develops in a different manner in each tissue, suggesting differential regulation of alpha 1-subunit expression.

The powerful genetic polymorphism of the HLA system has been used to identify individuals and populations. Ethnic groups may be characterized by specific HLA allele frequencies and particular extended HLA haplotypes; also, genetic relationships among these groups may be deduced. In the present study, serology and DNA typing were used to detect HLA-A, -B, -C, -DR, and -DQ alleles in each individual and to calculate characteristic haplotypes in Algerians. These results were compared to those previously obtained in other populations, particularly northern Mediterraneans; genetic distances and their respective dendrograms place Basques and Spaniards closer to Algerians than to other Europeans. Also, characteristic Basque and/or Spanish haplotypes are found in Algerians; i.e., A30-B18-Cw5-DR3-DQ2 and A1-B57-Cw7-DR7-DQ2. This supports the evidence that the Algerian population, mainly its paleo-North African component (Berbers), has a common descent with Basques and Spaniards, probably reflecting a preneolithic relationship between Iberians and paleo-North Africans.

Vaginal leiomyosarcoma is a very rare tumor. The authors report a case of primary presentation in a 51-year-old multipara who complained of the development, since about 12 months previously, of a vaginal swelling accompanied by bloody discharge and pain. The outcome was fatal twenty two months later following treatment combining chemotherapy, radiotherapy, and surgery. The case is discussed in the light of data from the literature.

The activity of an out-patient nephrology service during a period lasting from January 1991 to December 1993 (both inclusive) was studied. During this period, an average of 531 patients per million population and year were looked after, with a prevalence of 1,949 p.m.p. of chronic patients. Eleven point six per cent of the patients were discharged and 2.6% initiated treatment with hemodialysis, deducting nonappearances after examination, 66.9% of the patients were referred to permanent follow-up. Sixty seven point five per cent of the patients were older than 40 years and 31.2%, older than 60. The most frequent causes of consultation were AHT (17.4%), nephroangiosclerosis (5.7%), renal lithiasis (16.8%), idiopathic glomerulonephritis (10.9%) and diabetic nephropathy (8.2%). Fifty eight point five per cent of the patients were susceptible of out-patient care, especially those seen due to hypertension and lithiasis. We conclude that a significant increase in the needs of specialized care may be forecasted for the next years, mainly for arterial hypertension. Most of these needs could be covered through out-patient nephrology services.

Background: In response to nonspecific inflammatory stimuli, circulating monocytes produce several cytokines that regulate the expression of liver acute phase protein genes. Patients with alcoholic liver disease have several manifestations of the acute phase response, including elevated serum levels of interleukin (IL)-1 (IL-1), IL-6 and tumor necrosis factor-alpha (TNF-alpha). However, the role of the acute phase response on liver fibrogenesis has not been explored., Experimental Design: In this communication we report experiments performed to investigate whether turpentine, an acute phase response inducer in rats has any effect on alpha 1 (I) procollagen gene expression in the liver. We also investigated which of the cytokines is responsible for the turpentine effect and whether IL-6 and TNF-alpha had an effect on alpha 1 (I) procollagen mRNA expression by liver fat-storing cells (FSC)., Results: We show that alpha 1 (I) procollagen mRNA is increased in livers of turpentine-treated rats, and that an antibody to IL-6 as well as colchicine inhibit this effect. We also show that rIL-6 induces the expression of alpha 1 (I) procollagen mRNA in cultured FSC but not in hepatocytes. We demonstrated that the IL-6 effect is a transcriptional event that requires "de novo" protein synthesis. In addition to its effect on collagen gene expression, rIL-6 also stimulates expression of transforming growth factor-beta and fibronectin mRNAs. TNF-alpha inhibits alpha 1 (I) procollagen expression in FSC by 24 to 48 hours. However, TNF-alpha induces a transient expression of alpha 1 (I) procollagen mRNA by 2 to 3 hours. This increase is preceded by the induction of IL-6 mRNA., Conclusions: We conclude that IL-6 produced during the acute phase response, alone or in conjunction with other cytokines, could play an important role in liver fibrogenesis by inducing the expression of collagen, fibronectin, and transforming growth factor-beta mRNAs in FSC.

We present the case of an "idiopathic" edema induced by the chronic use of diuretics in a 44-years-old patient. The patient showed a significant secondary hyperaldosteronism which have been erroneousley labelled as primary in previous studies. The pathogenicity of the idiopathic edema and its relation to diuretic abuse are discussed.

The purpose of our study was to quantify the blood-retinal barrier permeability in five patients with insulin-dependent diabetic (mean age 14.96 +/- 2.45 years) without retinopathy, after six month with oral pirenzepine, a growth hormone inhibitor. Blood-retinal barrier permeability was determined by vitreous fluorophotometry before and after treatment with a nocturnal oral dose of pirenzepine (0.6 mg/kg the first month and 1 mg/kg the following five months). We found a significant diminution (p < 0.05) in growth hormone levels (10.48 +/- 4.94 ng/ml before treatment and 4.35 +/- 2.53 ng/ml after treatment), nevertheless, no changes in the blood-retinal barrier permeability values were observed (4.84 +/- 2.08 x 10(-6) min-1 before treatment and 4.53 +/- 2.54 x 10(-6) min-1 after treatment). We found no modifications in the levels of somatomedin C or HbA1c either. It can be concluded that oral pirenzepine used at this dose for six months, in spite of a significant decrease in growth hormone secretion, does not decrease the permeability of the blood-retinal barrier.

The appearance of toxic effects upon consumption of delayed release verapamil at therapeutic doses (120 mg/12 h) in a 64 year old patient with renal failure is described. The patient presented hypotension, bradycardia due to auriculoventricular block, hepatotoxicity, slight hyperglycemia, hyperpotassemia and metabolic acidosis with increased anionic gap. The picture remitted spontaneously with support treatment following discontinuation of the medication. The pathogenesis of the syndrome and the possibility that the hepatotoxicity was the triggering factor are discussed. Extreme precaution is recommended when this type of drugs is used in severe uremic or diabetic patients.

We describe the case of a 42-year-old woman diagnosed of chronic renal failure secondary to sarcoidosis. Since the beginning of the dialysis treatment she presented episodes of symptomatic hypercalcemia which did not response to calcium restriction diet and a lower calcium concentration in the dialysate. Secondary hyperparathyroidism and aluminium intoxication were biochemically ruled out. Hypercalcemic crisis were associated to 1.25-dihydroxy-vitamin D (1.25-D) serum levels abnormally raised and they responded quickly to low doses of corticosteroids. Subsequently, this treatment had to be withdrawn because of upper gastrointestinal bleeding, and hypercalcemia recurred. Chloroquine phosphate was prescribed with a rapid response to normalize the serum calcium levels. No side effects was recorded. Twelve months later of chloroquine therapy, the patient remained normocalcemic. A bone biopsy showed an active osteopenia without aluminium deposits, hyperparathyroidism signs or granuloma. We discuss about the pathogenesis of hypercalcemia in this case and its relation with abnormal high serum levels of 1.25-D in hemodialysis patients and sarcoidosis.

One observation of severe laryngeal papillomatosis is reported. After diagnosis by biopsy and tracheostomy the patient was treated with bleomycin and thio-tepa associated with punch extirpation of residual papillomata following Kleinsasser. Results at two and half years were excellent.