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Biomedical subjects

M Merino

Publications and source records attributed to M Merino.

At least 19 recordsLinked to original sources

Clinical efficacy of anti-pneumococcal vaccination in patients with COPD.

BACKGROUND: A study was undertaken to evaluate the clinical efficacy of the 23-valent pneumococcal polysaccharide vaccine (PPV) in immunocompetent patients with chronic obstructive pulmonary disease (COPD). METHODS: A randomised controlled trial was carried out in 596 patients with COPD of mean (SD) age 65.8 (9.7) years, 298 of whom received PPV. The main outcome was radiographically proven community acquired pneumonia (CAP) of pneumococcal or unknown aetiology after a mean period of 979 days (range 20-1454). RESULTS: There were 58 first episodes of CAP caused by pneumococcus or of unknown aetiology, 25 in the intervention group and 33 in the non-intervention group. Kaplan-Meier survival curves for CAP did not show significant differences between the intervention and non-intervention arms (log rank test = 1.15, p = 0.28) in the whole group of patients. The efficacy of PPV in all patients was 24% (95% CI -24 to 54; p = 0.333). In the subgroup aged <65 years the efficacy of PPV was 76% (95% CI 20 to 93; p = 0.013), while in those with severe functional obstruction (forced expiratory volume in 1 second <40%) it was 48% (95% CI -7 to 80; p = 0.076). In younger patients with severe airflow obstruction the efficacy was 91% (95% CI 35 to 99; p = 0.002). There were only five cases of non-bacteraemic pneumococcal CAP, all in the non-intervention group (log rank test = 5.03; p = 0.025). Multivariate analysis gave a hazard ratio for unknown and pneumococcal CAP in the vaccinated group, adjusted for age, of 0.20 (95% CI 0.06 to 0.68; p = 0.01). CONCLUSIONS: PPV is effective in preventing CAP in patients with COPD aged less than 65 years and in those with severe airflow obstruction. No differences were found among the other groups of patients with COPD.

Adult↗

[Skull base meningiomas: a predictive system to know the extent of their surgical resection and patient outcome].

OBJECTIVE: The aim of this study was to build a preoperative predictive system which could provide reliable information about: 1 degrees which skull base meningiomas can be total or partially removed, and 2 degrees their surgical outcome. METHOD: Patient histories and imaging data were reviewed retrospectively from 85 consecutive skull base meningiomas patients who underwent surgery from 1990 and 2002. From the preoperative data, nine variables were selected for conventional statistical analysis as regards their relationship with: 1 degrees total vs partial tumor resection and 2 degrees with patients outcome according to the degree of tumour removal. RESULTS: From the nine variables analysed only two had a statistical association with the type of tumour resection performed (total vs partial) and the patient outcome: 1) arteries encasement and 2) cranial nerves involvement. Upon correlating these two variables with the type of tumour resection performed (total vs partial) and with the Karnofsky'scale to evaluate patients surgical outcome, the following grading groups were identified: Grade I: skull base meningiomas which did not involve cranial nerves or artery or only encased one artery or one cranial nerve. In these cases the incidence of gross tumour resection was 98.3% (p< 0.0001) and the perspective to reach 70 points in the Karnofsky'scale was of 96.5% ( p=0.001). Grade II: skull base meningiomas which involved one cranial nerve and encased, at least, two main cerebral arteries. In these cases, the frequency of total resection, decreased to 83.3% (p<0.0001) and the probability to reach 70 points in the Karnofsky'scale was 70.6% (p=0.001). Grade III: skull base meningiomas which involved two or more cranial nerves and encased several arteries In this group, the frequency of a total resection was of 42.9% (p<0.0001) and the probability of reaching 70 points in the Karnofsky'scale was only 60% (p=0.001). CONCLUSIONS: We propose a preoperative grading system for skull base meningiomas that helps predicting both whether total or partial tumor removal will be achieved during surgery and the immediate postsurgical outcome of the patient. In applying this predictive system we will be able to reduce surgical morbidity, to advance the possibility of a radiosurgical treatment and give a more precise information to the patients and their families about our surgical decision-making process.

Adolescent↗

Interactions of oxyphenbutazone with different cyclodextrins in aqueous medium and in the solid state.

The interactions between a nonsteroidal anti-inflammatory drugs, oxyphenbutazone (OPB), with two cyclodextrins, beta-cyclodextrin (beta-CD) and gamma-cyclodextrin (gamma-CD), have been studied in an aqueous medium and in the solid state. Differential scanning calorimetry, hot stage microscopy, thermogravimetric analysis and X-ray diffraction (XRD) powder have been the techniques used to characterize the interactions in the solid state. Although OPB forms inclusion compounds with beta- and gamma-CD in the aqueous medium, only the OPB/gamma-CD inclusion compound was obtained in the solid state by the kneading method. The XRD powder used at different temperatures has proven be a useful tool in characterizing the behaviour of these binary systems.

Anti-Inflammatory Agents, Non-Steroidal↗

A Phase I study of infusional vinblastine in combination with the P-glycoprotein antagonist PSC 833 (valspodar).

BACKGROUND: PSC 833 is a second-generation P-glycoprotein (Pgp) antagonist developed to reverse multidrug resistance (MDR). The authors conducted a Phase I study of orally administered PSC 833 in combination with vinblastine administered as a 5-day continuous infusion. METHODS: Seventy-nine patients with advanced malignant disease were enrolled in the trial and treated with escalating doses of PSC 833. Pharmacokinetic interactions between PSC 833 and vinblastine were anticipated. Accordingly, when dose limiting toxicities were observed, the dose of vinblastine was reduced as PSC 833 was escalated. Three schedules and two formulations of PSC 833 were used in the study. RESULTS: The maximum tolerated doses of PSC 833 were 12.5 mg/kg orally every 12 hours for 8 days for the liquid formulation in combination with 0.9 mg/m(2) per day vinblastine as a continuous intravenous infusion (CIV) for 5 days; and 4 mg/kg orally every 6 hours for 8 days for the microemulsion formulation in combination with 0.6 mg/m(2) per day vinblastine CIV for 5 days. The principal toxicities for PSC 833 were ataxia and paresthesias and for the combination, constipation, fever. and neutropenia. Increased oral bioavailability and increased peak and trough concentrations were observed with the microemulsion formulation. Significant interpatient variability in pharmacokinetic parameters was observed. Ten patients studied at the MTD for PSC 833 (4 mg/kg orally every 6 hours for 8 days) had inhibition of rhodamine efflux from CD56 positive peripheral lymphocytes as a surrogate for Pgp antagonism. Among 43 evaluable patients with clear cell carcinoma of the kidney, 3 patients had complete responses, and 1 patient had a partial response. CONCLUSIONS: PSC 833 in combination with vinblastine can be administered safely to patients provided the vinblastine dose is adjusted for pharmacokinetic interactions. The high interpatient variability is a significant confounding factor. Surrogate studies with CD56 positive cells suggest that Pgp inhibition in the clinical setting is achievable. Improved methods for predicting pharmacokinetic interactions should improve future studies.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Birt-Hogg-Dubé syndrome, a genodermatosis associated with spontaneous pneumothorax and kidney neoplasia, maps to chromosome 17p11.2.

Birt-Hogg-Dubé syndrome (BHD), an inherited autosomal genodermatosis characterized by benign tumors of the hair follicle, has been associated with renal neoplasia, lung cysts, and spontaneous pneumothorax. To identify the BHD locus, we recruited families with cutaneous lesions and associated phenotypic features of the BHD syndrome. We performed a genomewide scan in one large kindred with BHD and, by linkage analysis, localized the gene locus to the pericentromeric region of chromosome 17p, with a LOD score of 4.98 at D17S740 (recombination fraction 0). Two-point linkage analysis of eight additional families with BHD produced a maximum LOD score of 16.06 at D17S2196. Haplotype analysis identified critical recombinants and defined the minimal region of nonrecombination as being within a <4-cM distance between D17S1857 and D17S805. One additional family, which had histologically proved fibrofolliculomas, did not show evidence of linkage to chromosome 17p, suggesting genetic heterogeneity for BHD. The BHD locus lies within chromosomal band 17p11.2, a genomic region that, because of the presence of low-copy-number repeat elements, is unstable and that is associated with a number of diseases. Identification of the gene for BHD may reveal a new genetic locus responsible for renal neoplasia and for lung and hair-follicle developmental defects.

Abnormalities, Multiple↗

Phase I clinical trial of alitretinoin and tamoxifen in breast cancer patients: toxicity, pharmacokinetic, and biomarker evaluations.

PURPOSE: To determine the overall and dose-limiting toxicities (DLTs) of alitretinoin (9-cis-retinoic acid) in combination with tamoxifen and the pharmacokinetics of alitretinoin alone and when combined with tamoxifen in patients with metastatic breast cancer. The effect of tamoxifen and alitretinoin on MIB-1, a marker of proliferation, in unaffected breast tissue was explored. PATIENTS AND METHODS: Eligible patients had metastatic breast cancer. Previous tamoxifen therapy was allowed. Planned dose levels for alitretinoin ranged from 50 to 140 mg/m2/d with 20 mg/d tamoxifen in all patients after 4 weeks of alitretinoin as a single agent. Plasma concentrations of alitretinoin and retinol were measured at baseline and after 1, 2, and 3 months. Breast core biopsies were obtained at baseline and after 2 months of therapy. RESULTS: Twelve patients with metastatic breast cancer received a total of 86 cycles of therapy. At 90 mg/m2/d, three of five patients experienced a DLT: grade 3 headache, grade 3 hypercalcemia, and grade 3 noncardiogenic pulmonary edema. At 70 mg/m2/d, one of six patients experienced a DLT (headache), and this level was considered the maximal tolerated dose in this study. Three toxicities occurred that had not been reported previously with alitretinoin: an asymptomatic delay in dark adaptation, a marked decrease in high-density lipoprotein cholesterol, and the occurrence of enthesopathy. Two of the nine assessable patients had a durable clinical response: one partial response and stable disease for 18 months and one complete response in continuous remission for 48+ months. Both responding patients were estrogen receptor-positive and had had previous tamoxifen therapy. There was a high degree of interpatient variability of plasma alitretinoin concentrations, although a significant decline in alitretinoin plasma levels over time was observed. MIB-1 scores declined in four of the eight paired breast specimens obtained. CONCLUSION: The combination of tamoxifen and alitretinoin is well tolerated and has antitumor activity in metastatic breast cancer. The recommended phase II dose is 70 mg/m2/d with 20 mg/d tamoxifen.

Adult↗

Phase I study of infusional paclitaxel in combination with the P-glycoprotein antagonist PSC 833.

PURPOSE: PSC 833 (valspodar) is a second-generation P-glycoprotein (Pgp) antagonist developed to reverse multidrug resistance. We conducted a phase I study of a 7-day oral administration of PSC 833 in combination with paclitaxel, administered as a 96-hour continuous infusion. PATIENTS AND METHODS: Fifty patients with advanced cancer were enrolled onto the trial. PSC 833 was administered orally for 7 days, beginning 72 hours before the start of the paclitaxel infusion. Paclitaxel dose reductions were planned because of the pharmacokinetic interactions known to occur with PSC 833. RESULTS: In combination with PSC 833, maximum-tolerated doses were defined as paclitaxel 13.1 mg/m(2)/d continuous intravenous infusion (CIVI) for 4 days without filgrastim, and paclitaxel 17.5 mg/m(2)/d CIVI for 4 days with filgrastim support. Dose-limiting toxicity for the combination was neutropenia. Statistical analysis of cohorts revealed similar mean steady-state concentrations (C(pss)) and areas under the concentration-versus-time curve (AUCs) when patients received paclitaxel doses of 13.1 or 17.5 mg/m(2)/d for 4 days with PSC 833, as when they received a paclitaxel dose of 35 mg/m(2)/d for 4 days without PSC 833. However, the effect of PSC 833 on paclitaxel pharmacokinetics varied greatly among individual patients, although a surrogate assay using CD56+ cells suggested inhibition of Pgp was complete or nearly complete at low concentrations of PSC 833. Responses occurred in three of four patients with non-small-cell lung cancer, and clinical benefit occurred in five of 10 patients with ovarian carcinoma. CONCLUSION: PSC 833 in combination with paclitaxel can be administered safely to patients provided the paclitaxel dose is reduced to compensate for the pharmacokinetic interaction. Surrogate studies with CD56+ cells indicate that the maximum-tolerated dose for PSC 833 gives serum levels much higher than those required to block Pgp. The variability in paclitaxel pharmacokinetics, despite complete inhibition of Pgp in the surrogate assay, suggests that other mechanisms, most likely related to P450, contribute to the pharmacokinetic interaction. Future development of combinations such as this should include strategies to predict pharmacokinetics of the chemotherapeutic agent. This in turn will facilitate dosing to achieve comparable CPss and AUCs.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Feature subset selection by genetic algorithms and estimation of distribution algorithms. A case study in the survival of cirrhotic patients treated with TIPS.

The transjugular intrahepatic portosystemic shunt (TIPS) is an interventional treatment for cirrhotic patients with portal hypertension. In the light of our medical staff's experience, the consequences of TIPS are not homogeneous for all the patients and a subgroup dies in the first 6 months after TIPS placement. Actually, there is no risk indicator to identify this subgroup of patients before treatment. An investigation for predicting the survival of cirrhotic patients treated with TIPS is carried out using a clinical database with 107 cases and 77 attributes. Four supervised machine learning classifiers are applied to discriminate between both subgroups of patients. The application of several feature subset selection (FSS) techniques has significantly improved the predictive accuracy of these classifiers and considerably reduced the amount of attributes in the classification models. Among FSS techniques, FSS-TREE, a new randomized algorithm inspired on the new EDA (estimation of distribution algorithm) paradigm has obtained the best average accuracy results for each classifier.

Algorithms↗

Histamine infusion induces a selective dopaminergic neuronal death along with an inflammatory reaction in rat substantia nigra.

We have evaluated the effects of a direct infusion of histamine, as mediator of inflammatory response, in substantia nigra, striatum, medial septum, and medial lemniscus. Injection of 100 and 250 nmol of histamine in substantia nigra produced a selective damage in dopaminergic neurons evidenced by the loss of tyrosine hydroxylase mRNA-expressing cells, tyrosine hydroxylase-immunolabeled-positive cell bodies, and dopamine and 3,4-dihydroxyphenylacetic acid levels. In parallel we found an acute inflammatory response manifested by a loss of glial fibrillary acidic protein-immunolabeled astrocytes and, at precisely the same area, an activation of microglia. In the striatum, only high doses (500 nmol) produced an evident terminal degeneration. The selective neurotoxicity of histamine for dopaminergic cells was demonstrated by the unaltered transcription of glutamic acid decarboxylase mRNA in substantia nigra. Moreover, intraseptal injection of 100 nmol of histamine failed to alter the pattern of choline acetyltransferase mRNA-expressing cells, and intraparenchymal injection of histamine in medial lemniscus failed to alter the pattern of serotonin-immunolabeled cells. We conclude that the substantia nigra is highly sensitive to histamine-derived neurotoxicity, where inflammatory processes mediated by histamine could be important in the pathological changes that lead to dopaminergic neuronal damage after histamine infusion.

3,4-Dihydroxyphenylacetic Acid↗

A single mid-follicular dose of CDB-2914, a new antiprogestin, inhibits folliculogenesis and endometrial differentiation in normally cycling women.

Previous studies in women have shown that the antiprogestin mifepristone delays or inhibits folliculogenesis. The purpose of this study was to explore whether a new analogue, CDB-2914, has similar effects on folliculogenesis, ovulation, or on subsequent luteal phase endometrial maturation. Forty-four normally cycling, healthy women recorded urine LH and vaginal bleeding during pre-treatment, treatment, and post-treatment cycles. At a lead follicle diameter of 14-16 mm, a single oral dose (10, 50, 100 mg) of CDB-2914 or placebo was given, and daily ultrasound, oestradiol and progesterone were obtained until follicular collapse; an endometrial biopsy was obtained 5-7 days later. Single doses of CDB-2914 were well tolerated. Mid-follicular CDB-2914 suppressed lead follicle growth, causing a dose-dependent delay in folliculogenesis and suppression of plasma oestradiol. At higher doses, a new lead follicle was often recruited. Although luteinized unruptured follicles were observed at the 100 mg dose, all women had follicular collapse. There was a significant delay in endometrial maturation after CDB-2914 at all doses. The treatment cycle was lengthened by 1-2 weeks in 30% at 100, 27% at 50 and 9% at 10 mg. CDB-2914 altered ovarian and endometrial physiology without major effects on menstrual cyclicity and may have therapeutic utility.

Adolescent↗

Vaginal 5-fluorouracil for high-grade cervical dysplasia in human immunodeficiency virus infection: a randomized trial.

OBJECTIVE: To compare the efficacy and toxicity of topical vaginal 5-fluorouracil (5-FU) maintenance therapy against the effects of observation after standard treatment for high-grade cervical dysplasia in human immunodeficiency virus (HIV)-infected women and to evaluate the association between baseline CD4 count and time to recurrence. METHODS: In a phase III unmasked, randomized, multicenter, outpatient clinical trial, 101 HIV-positive women either received 6 months of biweekly treatment with vaginal 5-FU cream (2 g) or underwent 6 months of observation after standard excisional or ablative cervical treatment for cervical intraepithelial neoplasia (CIN). Papanicolaou smears and colposcopy were scheduled at regular intervals during the ensuing 18 months, with the primary end point being the time at which CIN of any grade recurred. RESULTS: Thirty-eight percent of women developed recurrence: 14 (28%) of 50 in the 5-FU therapy group and 24 (47%) of 51 in the observation group. Treatment with 5-FU was significantly associated with prolonged time to CIN development (P = .04). Observation subjects were more likely to have high-grade recurrences, with 31% developing CIN 2-3 compared with 8% in the 5-FU treatment arm (P = .014), and disease recurred more quickly in observation subjects as well. Baseline CD4 count was related significantly to time to recurrence (P = .04), with 46% of subjects with CD4 counts less than 200 cells/mm3 developing recurrence compared with 33% of subjects with CD4 counts at least 200 cells/mm3. Disease recurred more slowly in subjects who had received antiretroviral therapy than in antiretroviral therapy-naive subjects. There were no instances of grade 3 or 4 toxicity, and compliance with 5-FU treatment was generally good. CONCLUSION: Adjunctive maintenance intravaginal 5-FU therapy after standard surgery for high-grade lesions safely and effectively reduced recurrence of cervical intraepithelial neoplasia in HIV-infected women.

Administration, Intravaginal↗

Unusual form of recurrent giant cell granuloma of the mandible and lower extremities in a patient with neurofibromatosis type 1.

We report on a girl with familial neurofibromatosis type 1 (Nf1) who at age 11 had multiple osteolytic lesions of the right mandible and the distal femoral and proximal tibial metaphyses bilaterally. No other skeletal component was affected, and no abnormalities were present on skeletal radiographs of her parents. Histologic examination of the mandibular and right femoral lesions revealed a "multinucleated giant cell process." Results of repeated routine laboratory and bone metabolic studies were within normal limits. The lack of reliable histologic criteria and the diagnostic problems in distinguishing among central giant cell granulomata, giant cell tumors of the jaw, cherubism, brown tumors resulting from (occult) hyperparathyroidism, Jaffe-Campanacci syndrome, McCune-Albright syndrome, Noonan-like/multiple giant cell lesion syndrome, and multiple nonossifying fibromas of bone are discussed.

Bone Diseases, Developmental↗

Tamoxifen and fenretinide in women with metastatic breast cancer.

BACKGROUND: Tamoxifen and fenretinide combination therapy has been shown to be an active treatment regimen in metastatic breast cancer patients. This pilot study sought to determine whether the addition of fenretinide to tamoxifen would be associated with antitumor activity in metastatic breast cancer patients who had been previously treated with tamoxifen or who had hormone receptor negative disease. The effect of this therapy on circulating plasma transforming growth factor-beta (TGF-beta) levels and serum lipids was also examined. PATIENTS AND METHODS: Thirty-one patients were treated with tamoxifen (20 mg p.o. daily), and fenretinide (400 mg p.o. daily with a 3-day drug holiday each month). Plasma TGF-beta testing was performed using isoform specific sandwich ELISA. RESULTS: Twenty four of the 31 patients were evaluable for an antitumor response including 14 estrogen receptor (ER) positive patients who had failed prior tamoxifen therapy, seven ER-negative patients, and three hormone therapy naive ER-positive patients. There were no objective antitumor responses; three patients had stable disease for 8, 8, and 24 months. Five patients (16%) discontinued therapy for toxicity (one for grade 3 skin rash and four for abnormal dark adaptation). There was a statistically significant decrease in total cholesterol (median change per patient of -13.5 mg/dl; p = 0.049, a 6.5% decrease), and an increase in HDL levels (median change per patient of +18 mg/dl, p = 0.0001, a 35% increase) with tamoxifen and fenretinide therapy. TGF-beta1 plasma levels were normal in 26 of 28 patients, and no changes in these levels post-treatment were demonstrated. CONCLUSIONS: Tamoxifen and fenretinide therapy is not an active combination in ER negative metastatic breast cancer or in patients whose disease has progressed on tamoxifen. This combination had a beneficial effect on total serum cholesterol and HDL levels with no associated rise in serum triglyceride levels. The 400 mg dose of fenretinide was associated with symptomatic nyctalopia in one-third of patients making it an unsuitable dose for use in breast cancer prevention studies.

Adult↗

The non-NMDA glutamate receptor antagonists 6-cyano-7-nitroquinoxaline-2,3-dione and 2,3-dihydroxy-6-nitro-7-sulfamoylbenzo(f)quinoxaline, but not NMDA antagonists, block the intrastriatal neurotoxic effect of MPP+.

Altered glutamatergic neurotransmission appears to be central to the pathophysiology of Parkinson's disease; consequently, considerable effort has been made to elucidate neuroprotective mechanisms against such toxicity. In the present study, the possible neuroprotective effect of glutamate receptor antagonists against MPP+ neurotoxicity on dopaminergic terminals of rat striatum was investigated. Different doses of glutamate receptor antagonists were coinfused with 1.5 microg of MPP+ into the striatum; kynurenic acid, a nonselective antagonist of glutamate receptors (30 and 60 nmol), partially protected dopaminergic terminal degeneration in terms of rescue of dopamine levels and tyrosine hydroxylase immunohistochemistry. Dizocilpine, a channel blocker of the NMDA receptor (1, 4, and 8 nmol), and 7-chlorokynurenic acid, a selective antagonist at the glycine site of the NMDA receptor (1 and 10 nmol), failed to protect dopaminergic terminals from MPP+ toxicity. However, 6-cyano-7-nitroquinoxaline-2,3-dione (0.5 and 1 nmol) and 2,3-dihydroxy-6-nitro-7-sulfamoylbenzo(f)quinoxaline (1 nmol), two AMPA-kainate receptor antagonists, protected against MPP toxicity. Our findings suggest that the toxic effects of MPP+ on dopaminergic terminals are not mediated through a direct interaction with the NMDA subtype of glutamate receptor, but with the AMPA-kainate subtype.

1-Methyl-4-phenylpyridinium↗

Familial renal oncocytoma: clinicopathological study of 5 families.

PURPOSE: We analyzed familial renal oncocytoma to provide a foundation for studies aimed at defining genes involved in the pathogenesis of renal oncocytoma. MATERIALS AND METHODS: We describe 5 families with multiple members affected with renal oncocytoma. Tumors were analyzed pathologically, and affected and nonaffected members were screened clinically and genetically. RESULTS: We identified 12 affected male and 3 affected female (ratio 4:1) individuals in the 5 families. In affected family members renal oncocytomas were often multiple and bilateral. No metastatic disease was observed. Most renal oncocytomas were detected incidentally in asymptomatic individuals or during screening of asymptomatic members of renal oncocytoma families. One identical twin pair was affected with bilateral multiple renal oncocytomas. CONCLUSIONS: Renal oncocytoma may be inherited in some families.

Adenoma, Oxyphilic↗

Conservation genetics of the endangered Pampas deer (Ozotoceros bezoarticus).

The Pampas deer (Ozotoceros bezoarticus L. 1758) is the most endangered neotropical cervid, and in the past occupied a wide range of open habitats including grassland, pampas, savanna, and cerrado (Brazil) from 5 degrees to 41 degrees S. To better understand the effect of habitat fragmentation on gene flow and genetic variation, and to uncover genetic units for conservation, we examined DNA sequences from the mitochondrial control region of 54 individuals from six localities distributed throughout the present geographical range of the Pampas deer. Our results suggest that the control region of the Pampas deer is one of the most polymorphic of any mammal. This remarkably high variability probably reflects large historic population sizes of millions of individuals in contrast to numbers of fewer than 80,000 today. Gene flow between populations is generally close to one migrant per generation and, with the exception of two populations from Argentina, all populations are significantly differentiated. The degree of gene flow was correlated with geographical distance between populations, a result consistent with limited dispersal being the primary determinant of genetic differentiation between populations. The molecular genetic results provide a mandate for habitat restoration and reintroduction of Pampas deer so that levels of genetic variation can be preserved and historic patterns of abundance can be reconstructed. However, the source of individuals for reintroduction generally should be from populations geographically closest to those now in danger of extinction.

Animals↗

Familial osteoma of the cranial vault.

A case of solitary osteoma of the parietal skull is described in a mother and her 12-year-old son. There were no other craniofacial or dysmorphic features and there was no history of previous cranial trauma or inflammatory process and no radiographic evidence of other skeletal lesions in both patients. Family history was otherwise unremarkable. Gardner syndrome was ruled out by excluding other associated clinical abnormalities and by family history. The clinical and radiological features of the patients' osteomas were different from those of Albright hereditary osteodystrophy, fibrodysplasia ossificans progressiva, progressive osseous heteroplasia and familial ectopic ossification. To the author's knowledge this is the first case of the familial presentation of osteomas.

Adolescent↗