Erdheim–Chester disease: An unusual presentation of an uncommon disease

Erdheim–Chester disease (ECD) is a rare, non-Langerhans cell histiocytosis with classic radiographic findings of patchy or diffuse osteosclerosis predominantly involving the long bones in a bilaterally symmetrical pattern. A 49-year-old woman presented with diffuse lymphadenopathy, painful skin lesions, and constitutional symptoms. Recent history was significant for a nontraumatic fracture of the tibia 3 weeks prior to admission. Physical examination and laboratory studies were notable for lower extremity pain and swelling, nodular lesions on the skin, and normocytic, normochromic anemia. Plain radiographs showed a lytic pattern of destruction with a superimposed fracture in the left proximal tibia. MRI showed focal bone marrow replacement extending from the subchondral bone to the tibial diaphysis. Excisional lymph node and skin biopsies of the lesions demonstrated a CD-68 positive, S-100 variable, and CD1a-negative histiocytic cell proliferation filling the dermis and completely replacing the sampled lymph node with an accompanying chronic inflammatory infiltrate and fibrosis, pathognomonic for ECD. We report an unusual case of ECD presenting initially as diffuse, painful lymphadenopathy, and subsequently demonstrating a lytic lesion of the tibia underlying a nontraumatic fracture.     

Comparison of two functional independence scales with a participation measure in post-stroke rehabilitation

The objectives of the study were to compare the association and responsiveness of the functional autonomy measurement system (SMAF) and functional independence measure (FIM) as outcome measures addressing functional independence in stroke patients involved in an intensive rehabilitation program and to compare their relationships with a social participation measure after rehabilitation period. One hundred and thirty-two people who had a stroke were evaluated with the SMAF and FIM during the rehabilitation period (T1: admission; T2: discharge; n=132) and twice after discharge (T3=2 weeks; n=118; T4=6 months later; n=102). At T3 and T4, a participation measure, the assessment of life habits (LIFE-H), was added. The main findings are: (1) the total scores on the SMAF and FIM are strongly correlated together (r=0.93 to 0.95; p<0.001); 2) the responsiveness of both functional independence scales is similar even though the SMAF total score is more responsive to change than the FIM total score (standardized response mean: 1.20 vs. 0.97; p<0.01); (3) the SMAF and FIM are related similarly to the daily activities domain of the participation scale; and finally (4) the social roles domain of the participation scale is less related to the SMAF and MIF than the daily activities domain; however, the SMAF score is more related to the social roles domain than the MIF. Our results support the need to use supplementary measures, such as participation measure, that cover not only physical function but also the other domains of participation, such as interpersonal relationships and leisure, that can be disrupted following a stroke.     

Aberrant membrane hormone receptors in incidentally discovered bilateral macronodular adrenal hyperplasia with subclinical Cushing's syndrome.

Cortisol secretion in adrenal Cushing's syndrome can be regulated by the aberrant adrenal expression of receptors for gastric inhibitory polypeptide, vasopressin, catecholamines, LH/human CG (LH/hCG), or serotonin. Four patients with incidentally discovered bilateral macronodular adrenal hyperplasia without clinical Cushing's syndrome were evaluated for the possible presence of aberrant adrenocortical hormone receptors. Urinary free cortisol levels were within normal limits, but plasma cortisol levels were slightly elevated at nighttime and suppressed incompletely after dexamethasone administration. Plasma ACTH was partially suppressed basally but increased after administration of ovine CRH. A 51-yr-old woman had ACTH-independent increases of plasma cortisol after 10 IU AVP im (292%), 100 microg GnRH iv (184%), or 10 mg cisapride orally (310%); cortisol also increased after administration of NaCl (3%), hCG, human LH, and metoclopramide. In a 61-yr-old man, cortisol was increased by AVP (349%), GnRH (155%), hCG (252%), and metoclopramide (191%). Another 53-yr-old male increased plasma cortisol after AVP (171%) and cisapride (142%). Cortisol secretion was also stimulated by vasopressin in a 54-yr-old female. This study demonstrates that subclinical secretion of cortisol can be regulated via the aberrant function of at least V1-vasopressin, LH/hCG, or 5-HT4 receptors in incidentally identified bilateral macronodular adrenal hyperplasia.     

Implementation of chemoprophylaxis of leprosy in the Southern Marquesas with a single dose of 25 mg per kg rifampin

Between 1967 and 1987 in the Southern Marquesas, a remote archipelago in French Polynesia, the detection rate of leprosy was 48.9 per 100,000 when it was 8.6 per 100,000 for French Polynesia as a whole. In 1988, a program of chemoprophylaxis of leprosy with a single dose of 25 mg/kg rifampin was implemented, and 2751 persons (98.7% of the population) were treated in the Southern Marquesas. In addition, 678 South Marquesans and 2466 members of their families living in the Northern Marquesas and in the Society Archipelago, received the same chemoprophylaxis. Among 2676 persons studied in the Southern Marquesas (97.4% of the treated population), 130 had elevated IgM anti-phenolic glycolipid-I antibodies by ELISA without any evidence of leprosy. The onset of a skin lesion of borderline leprosy in a boy 3 months after chemoprophylaxis raises the question of the nature of such a skin lesion and, indirectly, of the effectiveness of the chemoprophylaxis.     

Low vs Standard Pressures in Gynecologic Laparoscopy: a Systematic Review

Background:

The optimal intraperitoneal pressure during laparoscopy is not known. Recent literature found benefits of using lower pressures, but the safety of doing abdominal surgery with low peritoneal pressures needs to be assessed. This systematic review compares low with standard pneumoperitoneum during gynecologic laparoscopy.

Database:

We searched Medline, Embase, and the Cochrane Library for randomized controlled trials comparing intraperitoneal pressures during gynecologic laparoscopy. Two authors reviewed references and extracted data from included trials. Risk ratios, mean differences, and standard mean differences were calculated and pooled using RevMan5. Of 2251 studies identified, three were included in the systematic review, for a total of 238 patients. We found a statistically significant but modest diminution in postoperative pain of 0.38 standardized unit based on an original 10-point scale (95% confidence interval [CI], –0.67 to –0.08) during the immediate postoperative period when using low intraperitoneal pressure of 8 mm Hg compared with ≥12 mm Hg and of 0.50 (95% CI, –0.80 to –0.21) 24 hours after the surgery. Lower pressures were associated with worse visualization of the surgical field (risk ratio, 10.31; 95% CI, 1.29–82.38). We found no difference between groups over blood loss, duration of surgery, hospital length of stay, or the need for increased pressure.

Conclusion:

Low intraperitoneal pressures during gynecologic laparoscopy cannot be recommended on the behalf of this review because improvement in pain scores is minimal and visualization of the surgical field is affected. The safety of this intervention as well as cost-effectiveness considerations need to be further studied.     

Genetic studies of neuropeptide Y and neuropeptide Y receptors Y1 and Y5 regions in morbid obesity

Summary Synthesis and release of neuropeptide Y (NPY) are both regulated by leptin binding to its hypothalamic receptor mediating some of the effects of leptin on food intake. Moreover, NPY administration is a powerful stimulant of feeding behaviour. Thus, we investigated the potential implication of NPY, NPY-Y1 and -Y5 subtype receptors [rNPY-Y1/-Y5] in the development of human obesity. Two complementary genetic approaches were used: 1) linkage analyses between obesity and polymorphic markers located nearby NPY and rNPY-Y1/-Y5 genes (respectively on chromosomes 7p15.1 and 4q[31.3–32]) in 93 French Caucasian morbidly obese families; 2) single strand conformation polymorphism (SSCP) scanning of the coding region of the NPY and rNPY-Y1 genes performed in 50 unrelated obese patients ascertained on the basis of a body mass index of 27 kg/m² or more and a family history of obesity. No evidence of linkage between morbid obesity or obesity-related quantitative traits and NPY and rNPY-Y1/Y5 regions was found in this population. Moreover, SSCP scanning revealed no mutation in the coding region of NPY and rNPY-Y1 genes among obese subjects. These results suggest that NPY and NPY-Y1/Y5 receptors are unlikely to be implicated in the development of human morbid obesity, at least in the French Caucasian population. [Diabetologia (1997) 40: 671–675] Received: 27 December 1996 and in revised form: 26 February 1997     

Effects of EGIS-7625, a Selective and Competitive 5-HT2B Receptor Antagonist

Our aim was to specify the 5-HT(2) subtype selectivity of EGIS-7625 (1-benzyl-4-[(2-nitro-4-methyl-5-amino)-phenyl]-piperazine), a new 5-HT(2B) ligand, in receptor binding studies and characterize its pharmacology at 5-HT(2A), 5-HT(2B) and 5-HT(2C) receptors in in vivo experiments and in isolated organs, in vitro. EGIS-7625 had high affinity for recombinant human 5-HT(2B) receptors (pK(i) = 9.0) but much weaker affinity for 5-HT(2A) and 5-HT(2C) receptors (pK(i) = 6.2 and 7.7, respectively). In the classic 5-HT(2B) test, EGIS-7625 produced a concentration-related parallel rightward shift in the concentration-response relationship for the 5-HT-induced smooth muscle constriction in rat stomach fundus strips with a pA(2) of 9.4. On the other hand, EGIS-7625 was a weak competitive antagonist at 5-HT(2A) receptors as it shifted 5-HT-induced concentration-response curves to the right at high concentrations (pA(2) = 6.7) in rabbit pulmonary artery strips. The m-chlorophenylpiperazine-induced hypomotility and hypophagia was only partially attenuated by EGIS-7625 even at a dose of 30 mg/kg i.p. while mianserin, a non-selective 5-HT antagonist was almost fully effective in these tests at 3 mg/kg i.p., suggesting weak antagonistic effect of EGIS-7625 at neuronal 5-HT(2C) receptors, in vivo. In conclusion, EGIS-7625 is a potent, selective and competitive 5-HT(2B) antagonist that seems to be a good research tool for the separation of the functional roles of vascular 5-HT(2A) and 5-HT(2B) receptors.     

Synthesis and structure-affinity-activity relationships of novel benzofuran derivatives as MT(2) melatonin receptor selective ligands

A series of N-(2-phenylbenzofuran-3-yl) ethyl amide and N-(2-arylalkylbenzofuran-3-yl) ethyl amide derivatives were synthesized and evaluated as melatonin receptor ligands. The affinity of each compound for the two MT(1) and MT(2) melatonin receptor subtypes was determined by binding studies using 2-[(125)I]iodomelatonin on human embryonic kidney cell line HEK293 membrane homogenates. The intrinsic activity of the most interesting compounds was evaluated on the [(35)S]GTPgammaS binding assay. Introduction of a 2-phenyl substituent in the C-2 benzofuran position leads to an agonist compound, 10q, which binds more strongly than melatonin itself to both MT(1) and MT(2) subtypes. On the other hand, a 2-benzyl group in the same position allows MT(2) antagonist selective ligands to be obtained. The MT(2) selectivity and antagonist potency can be modulated with suitable modifications on the N-acyl and benzyl substituents, and the most selective compounds 10c and 19 show affinity ratios of 123 and 192, respectively, and bind to the MT(2) subtype similarly to melatonin itself (0.1 nM). Nevertheless, 10c acts as an MT(1) and MT(2) antagonist, whereas 19 is a partial agonist.