Bicompartmental (uni plus patellofemoral) versus total knee arthroplasty: a match-paired study.

BACKGROUND: Osteoarthritis (OA) of the knee, whether primary or post-traumatic, does not always involve all three compartments (tibiofemoral medial and lateral and the patellofemoral ones). Bicompartmental knee arthroplasty (BKA) was proposed as a good alternative to total knee arthroplasty when two of the three knee compartments were affected. MATERIALS AND METHODS: We performed a retrospective comparative study collecting all BKAs performed between March 2010 and January 2016. During this period, we treated 27 patients with BKA for medial or lateral and patellofemoral OA. Seven of them were lost to follow-up and were not included in the study. Group A (BKA group) was compared to a homogeneous group of 20 patients who underwent TKA during the same period (group B). RESULTS: Patients treated with TKA were younger than those treated with BKA (mean age 65 vs. 67.2; p = 0.2149). BKA resulted in longer mean operating time (87 vs. 82.4 min; p = 0.2983), less blood loss (413 vs. 458 ml; p = 0.0052) but higher blood transfusion rate (12 vs. 10%). Medium follow-up was 34 months for BKA group and 38 months for TKA group. No statistically significant differences were found in KSS score between the two groups (KSS score 92.3 for BKA, 94.5 for TKA; p = 0.5221; KSS function was 87.2 for BKA and 89.2 for TKA; p = 0.4985). CONCLUSION: The most important finding of the present study was that although BKA seemed to be theoretically more favorable in terms of functional recovery and blood loss, patients of group A had lower KSS score and higher transfusion rate than those of group B. Our data confirm that BKA could be proposed as an alternative to TKA, especially in young and high-demanding patients.

Commitment to the production of male and female gametocytes in the human malaria parasite Plasmodium falciparum.

Commitment to the production of female and male gametocytes was studied in the NF54 line of the human malaria parasite Plasmodium falciparum. The development of sibling parasites derived from individual schizonts was followed, and 2 antisera against the female gametocyte-specific protein Pfg377 and the male gametocyte-specific protein alpha-tubulin II were used to determine the sex of sibling gametocytes. The experiment showed that individual cohorts of sibling gametocytes were stained in a mutually exclusive fashion by only one or the other antiserum, indicating that individual schizonts committed to yield sexual parasite progeny produce gametocytes of the same sex. This work suggests that in P. falciparum commitment to sexual differentiation occurs prior to schizont maturation, at the same moment when the sex of the resulting gametocytes is determined.

Repetitive sequences upstream of the pfg27/25 gene determine polymorphism in laboratory and natural lines of Plasmodium falciparum.

The structure of the genomic region located upstream of the gametocyte-specific gene pfg27/25 of Plasmodium falciparum was analysed in laboratory lines and field isolates of the parasite. The gene is located in a subtelomeric region of chromosome 13 in parasite clones 3D7 and HB3. Analysis of laboratory lines and field isolates of P. falciparum indicated that polymorphism upstream of pfg27/25 is mainly due to the structure of a repetitive DNA region located at about half a kilobase from the pfg27/25 coding sequence. Different types of repetitive sequences are present in this region, whose copy number is variable in different parasite lines. In addition a GC-rich sequence element contained in this region, which is proposed to be the startpoint of pfg27/25 mRNA, presents either a direct or a reverse orientation in different parasite lines. Genomic deletions upstream of the pfg27/25 gene are also described in two laboratory lines of the parasite, which eliminate two newly identified malaria genes. orf P and orf Gap, from the genome of these parasites. One of them, orf Gap, deleted from the reference parasite clone 3D7, is abundantly expressed as mature mRNA in asexual parasites. PCR analysis on 64 field isolates of P. falciparum indicated that orf P and orf Gap sequences are present in all tested samples of naturally propagating parasites.

Genome plasticity and sexual differentiation in Plasmodium.

Spontaneous subtelomeric deletions of Plasmodium chromosomes have been observed both in natural infections and in laboratory maintained parasites. In the latter case, functions dispensable for asexual parasite multiplication and encoded at the extremities of the chromosomes are easily lost. In particular, spontaneous subtelomeric deletions have been characterised which affect gametocytogenesis both in Plasmodium berghei maintained in laboratory animals and in Plasmodium falciparum propagated in in vitro cultures. In order to identify these genetic determinants, and, potentially, other genes located subtelomerically, we designed a transfection system able to induce and select for controlled, site-specific subtelomeric deletions.

Californian hybrid zone between Culex pipiens pipiens and Cx. p. quinquefasciatus revisited (Diptera:Culicidae).

Phallosome morphology (DV/D ratio) and allozyme variation were used to reexamine the transition from Culex pipiens pipiens L. to Cx. p. quinquefasciatus Say, detected in California from the northern Central Valley to the Mexican border of the United States of America. Significant deficiency of heterozygotes was observed at the diagnostic locus Mdhp-2 in populations from the central part of the hybrid zone. Long tails of introgression were detected: populations from both north and south ends of the transect were not genetically pure Cx. p. pipiens or Cx. p. quinquefasciatus, respectively, as previously considered, but included approximately 5% introgressed individuals. A narrow reversed cline from the Delta area into the Sacramento Valley, characterized by increasing frequencies of Cx. p. quinquefasciatus alleles proceeding to the north, was confirmed. Both these cline appear to be related mainly to temperature gradients. Over the last 50 yr, an increase in the proportion of Cx. p. pipiens DV/D phenotypes was detected proceeding north to south along the main latitudinal cline, as well as in the narrow reversed cline. Accordingly, the center of the main latitudinal hybrid zone has apparently moved approximately 100 km to the south. This phenomenon is only partially paralleled by the differentiated locus Pgm of the 3 for which comparison was possible. Similarities to and differences from previous studies are discussed, also in relation with comparable data from another hybrid zone between Cx. p. pipiens and Cx. p. quinquefasciatus recently detected in Madagascar. Hybrid index scores based on differentiated allozymes and the diagnostic locus Mdhp-2 prove to be better descriptors than the DV/D ratio of hybridization and introgression occurring between Cx. p. pipiens and Cx. p. quinquefasciatus. This seems to be caused mainly by the influence of temperature on male genitalia development, and the weaker association found between genetic markers and DV/D phenotypes in hybrid populations.

Sequence and secondary structure of the rDNA second internal transcribed spacer in the sibling species Culex pipiens L. and Cx. quinquefasciatus Say (Diptera: Culicidae).

The primary and secondary structure of the second internal transcribed spacer (ITS2) of ribosomal DNA (rDNA) of two members of the Cx. pipiens complex, Cx. pipiens and Cx, quinquefasciatus, were examined in order to better understand the relationships between these two sibling mosquito species. The length of the sequenced rDNA fragments was 512 bp (Cx. pipiens) and 513 bp (Cx. quinquefasciatus), including the ITS2 regions and flanking 5.8S-28S coding regions. The ITS2 sequences of Cx. pipiens and Cx. quinquefasciatus were 297 and 298 bp in length respectively and showed a 97% identity. In fact, they had identical G+C content (58%) and the only differences observed are six mismatches (three transitions/three transversions), six single-base and one triple-base deletions/ insertions. The observed ITS2 secondary structures of Cx. pipiens and Cx. quinquefasciatus were very similar. Furthermore, the ITS2 sequences of specimens belonging to three populations of Cx. pipiens from Italy and four populations of Cx. quinquefasciatus (three from Africa and one from North America) were analysed in order to detect the presence of potential species-specific diagnostic restriction sites.

Structure and polymorphism of the upstream region of the pfg27/25 gene, transcriptionally regulated in gametocytogenesis of Plasmodium falciparum.

Transcription of the early gametocyte-specific gene pfg27/25, and genomic structure and polymorphism of its upstream region were studied in the human malaria parasite Plasmodium falciparum. The upstream genomic sequence of the pfg27/25 gene is characterised by a repetitive region that contains five direct and one inverted repeats of a unit constituted by a perfectly conserved sequence flanked by a poly-dT and a poly-d(AT) tract. Sequences further upstream from the repetitive region are polymorphic in distantly related parasite lines. Nuclear 'run off' experiments indicated that transcription of pfg27/25 is developmentally regulated. Transcription of the gene, undetectable in asexual parasites, is activated at the onset of gametocytogenesis. Te gene is transcribed in a 2.5 kb mature mRNA for the first 2-3 days of sexual differentiation, while transcription is down-regulated in more mature gametocytes.

Characterization of the Culex pipiens complex (Diptera: Culicidae) in Madagascar.

Morphological analysis of phallosome and multilocus electrophoresis were used to characterize populations of the Culex pipiens L. complex from Madagascar. Samples phenotypically and genetically corresponding to Cx. p. quinquefasciatus Say were found on the east and west coasts, whereas, on the high plateau, 1 sample was composed mostly of phenotypical Cx. p. pipiens L., genetically introgressed with quinquefasciatus at some loci (Hbdh, Aat-2, and Hk-1). A hybrid zone between the 2 taxa was detected on the plateau on a genetic basis, whereas at the morphological level a predominance of Cx. p. quinquefasciatus specimens and deficit of intermediates was observed. Accordingly, morphological analysis failed to describe satisfactorily the hybridization phenomena. Despite the high level of gene exchange, a complete mixing of the 2 gene pools apparently does not occur, possibly because of differential selective pressures in the climatically heterogeneous environment of the Madagascar plateau.

Preliminary report of a kindred affected from MEN IIa.

Preliminary data of a kindred with multiple endocrine neoplasia type IIa (MEN IIa) are presented. The study concerns 20 subjects belonging to 4 generations. The first is a man, previously adrenalectomized for pheochromocytoma, suffering from thyroid node with high serum calcitonin (CT) and normal tests for parathyroid function, who underwent total thyroidectomy, removal of a grossly enlarged parathyroid and subsequent autotransplantation, because the other glands seemed to be macroscopically uninvolved. In 4 further patients total thyroidectomy and removal of the parathyroid glands with autotransplantation were performed. In all patients, despite biochemical tests had disclosed parathyroid hyperfunction in only one, one or more enlarged parathyroid glands were found, subsequently diagnosed as adenomatous or with focal areas of "chief-cell" hyperplasia. In 3 out of 4 patients, a single test among those performed to detect the presence of a pheochromocytoma was positive. However, because of the lack of a clear correlation among data from biochemistry, stimulation tests and morphological investigations, adrenalectomy has not been performed. Nevertheless these patients will be closely followed up, in order to promptly state when andrenalectomy has to be performed.

Dopaminergic treatment of acromegaly: different effects on hormone secretion and tumor size.

We studied the effects of long term treatment with bromocriptine (Br) or lisuride (L) on GH secretion and tumor size in 19 acromegalic patients with large pituitary adenomas. In 22 additional patients with smaller adenomas, only plasma GH levels were monitored during treatment. All patients underwent an acute test with 2.5 mg Br or 0.3 mg L and, on the basis of GH changes, were classified as responders, i.e. reduction in circulating GH concentrations by at least 50% below baseline, or as nonresponders. The chronic treatment was 5-20 mg/day Br in 26 patients or 0.3-2.0 mg/day L in 15 patients. Treatment was given for 4-26 months (mean +/- SE, 13.3 +/- 2.8 months). Plasma GH levels (baseline, 46.3 +/- 8.3 ng/ml) were significantly lower in the group as a whole (22.7 +/- 3.6 ng/ml; P less than 0.01) after the first month of treatment with dopamine agonist agents. GH levels decreased significantly in those acromegalic patients who responded to the acute test (P less than 0.001), but were unchanged in the nonresponders. In addition, there was a significant correlation between the maximal percent GH decrease in the acute test and the response during chronic treatment (r = 0.73; P less than 0.01). Computed tomography failed to show any tumor size changes in any of the GH nonresponders who had a macroadenoma . However, in two patients in the acute responder group with macroadenomas, chronic dopamine agonist therapy resulted in reduction of the extrasellar portion of the tumor (-30% and -40% of tumor area, respectively). These data show that although dopaminergic drugs lower GH levels and reverse signs and symptoms of active disease in those acromegalic patients who are responsive to an acute challenge, tumor size reduction occurred in a minority of such patients.

Effects of nomifensine on growth hormone and prolactin secretion in normal subjects and in pathological hyperprolactinemia.

We have studied the effect of the oral administration of 200 mg nomifensine (nom), a drug which activates the dopaminergic system, on GH and PRL secretion in 15 normal subjects, 18 patients with idiopathic hyperprolactinemia, and 17 patients with tumoral hyperprolactinemia. GH levels increased significantly after nom in normal subjects (basal, 0.96 +/- 0.76 ng/ml; peak 4.6 +/- 0.61 ng/ml; P less than 0.01) and patients with hyperprolactinemia, both idiopathic (basal, 1.0 +/- 0.38 ng/ml; peak, 4.2 +/- 1.0 ng/ml; P less than 0.05) and tumoral (basal 0.88 +/- 0.3 ng/ml, peak 6.68 +/- 1.2 ng/ml; P less than 0.01). Peak GH levels higher than 5 ng/ml were observed in 8 of 15 normal subjects, 6 of 18 patients with idiopathic hyperprolactinemia, and 8 of 17 patients with tumoral hyperprolactinemia. PRL levels decreased in response to nom in normal subjects, but not in patients with idiopathic or tumoral hyperprolactinemia. A reduction in plasma PRL levels of at least 30% below the baseline was observed only in two patients with idiopathic hyperprolactinemia and in none of the patients with tumoral hyperprolactinemia. These results demonstrate that nom does not discriminate between idiopathic and tumoral hyperprolactinemia. Since nom probably requires a hypothalamic pool of dopamine to bring about its GH stimulatory effect, the suggestion that the lack of a PRL-lowering effect of the drug is attributable to a dopamine deficiency is not supported by our data.

Size reduction of macroprolactinomas by bromocriptine or lisuride treatment.

We have administered to 29 patients with macroprolactinoma the dopamine agonists bromocriptine and lisuride for 1-50 months (mean +/- SE, 12.7 +/- 1.8) in order to assess the effects of these drugs on tumor size. Fourteen patients were treated with bromocriptine (dose range, 7.5-20 mg/day), 12 patients were treated with lisuride (0.6-2 mg/day), and 3 patients were given both drugs. Computed tomography performed before and during treatment showed the occurrence of tumor shrinkage in 18 patients (62%), but in no case was a complete disappearance of the tumor observed. In 5 of these patients, it was even possible to document tumor shrinkage within the first month of treatment with low doses of the dopamine agonists, whereas in other patients, tumors shrank only after prolonged treatment with higher doses. Visual field and acuity improved or normalized in 8 of the 13 patients with visual defects; in some cases, the improvement was reported as early as 2 days after the treatment was started. Plasma PRL levels fell in all patients who showed a reduction in tumor size; in 2 other patients, PRL levels were only poorly suppressed, and tumor size remained unchanged. In the remaining patients, PRL levels were lowered without convincing evidence of tumor shrinkage. In considering the high percentage of patients showing tumor shrinkage under medical treatment, we propose a course with dopamine agonists as the first step in the management of patients with macroprolactinomas regardless of the presence of visual impairments.

Size reduction of a prolactin secreting adenoma during long-term treatment with the dopamine agonist lisuride.

A 38-year-old amenorrhoeic woman suffering from a prolactin (PRL) secreting adenoma, which had suprasellar extension as shown by caroe agonist (lisuride). PRL levels were lowered and after 1 year of treatment CAT showed a marked reduction of the tumour size. After 2 years of treatment menstruation returned and CAT demonstrated a further reduction of the adenomatous tissue. This study supports the suggestion that dopamine agonists possess an anti-proliferative effect on tumoural lactotrophic cells of humans.

Effect of ergot alkaloids on growth hormone and prolactin secretion in humans.

The effects of ergot alkaloids (mainly bromocriptine) on the secretion of GH and PRL in normal subjects and in pathological conditions (i.e. acromegaly and hyperprolactinemic states) are discussed. In the normal subjects, bromocriptine releases GH whereas in about 50% of acromegalics it causes a marked and long-lasting inhibition of the hormone secretion. PRL release is reduced by the drug both in normal subjects and in hyperprolactinemic states. Physiopathological studies in the humans indicate that, according to the experimental data, bromocriptine inhibits GH release in acromegaly and PRL secretion through a dopaminergic mechanism of action playing at the pituitary level. Data are reported on the effectiveness of bromocriptine in the medical treatment of acromegaly and of hyperprolactinemic states.

Long-term treatment with 2-Br-alpha-ergocryptine in acromegaly.

Thirty acromegalic subjects underwent chronic CB154 therapy (10-20 mg daily) for periods ranging from 3 months up to 2 years. In 18 out of 21 patients, who exhibited consistent HGH reduction following acute administration of the drug, there was also during chronic treatment, a suppression of the plasma HGH levels exceeding 50% of base line values, e.g. from mean daily values between 14-197 ng/ml (mean +/- SEM = 57.8 +/- 12.4 ng/ml pre-treatment) to 2-19 ng/ml (mean 8.3 +/- 1.2 ng/ml post-treatment). In 12 of the subjects who responsed to chronic CB154 treatment, the mean daily values of HGH were below 10 ng/ml. The suppression of plasma HGH was maintained unaltered throughout the whole course of therapy. In the 9 subjects, in whom no consistent HGH decrease was evidenced with acute CB154 administration, there was accordingly a minor or no suppression of HGH values during the chronic treatment. In 13 subjects, irrespective of the degree of their GH responses, the plasma prolactin levels were constantly inhibited by CB154; instead the drug failed to modify significantly the TRH or insulin-induced GH release. These changes in the hormonal parameters were paralleled by marked clinical amelioration and improvement of some of the metabolic alterations frequently encountered in acromegaly, e.g. reduced carbohydrate tolerance, increased insulin resistance, diminished fall of plasma phosphorus after insulin, decreased urinary excretion of phosphate, hyper-hydroxyprolinuria and hyper-calciuria. Collectively, these data demonstrate that CB154 thrapy is effective in reducing HGH hyper-secretion in many acromegalic patients during long-term treatment.