Gastric Sarcoid

An unusual presentation of sarcoidosis was noted in a patient who developed severe upper gastrointestinal hemorrhage. The bleeding was attributed to a sarcoid ulcer of the stomach. Serial gastroscopic studies demonstrated complete resolution of the ulcer within five months on conventional antacid therapy. The only residual lesions were gastric mucosal nodularities and moderate hyperemia with granulomas on biopsy. Sarcoidosis was diagnosed by positive Kveim test and abnormal diffusing lung capacity despite a normal chest roentgenogram.     

Randomized double‐blind placebo‐controlled crossover study to determine the effects of esomeprazole on inhibition of platelet function by clopidogrel

Summary. Background: Pharmacokinetic studies suggest that clopidogrel and esomeprazole are metabolized by similar hepatic enzymes; however, previous studies have not identified a biochemical interaction. Objectives: To determine whether addition of esomeprazole to patients receiving aspirin and clopidogrel reduces the antiplatelet effects of clopidogrel. Patient/Methods: Patients with a history of an acute coronary syndrome who had previously received clopidogrel were recruited. Subjects were commenced on clopidogrel and randomized to one of two treatment arms (esomeprazole or placebo) for 6 weeks. Following a 2‐week washout period for study medications, patients were crossed over onto the alternative treatment arm for a further 6 weeks. Platelet function tests were undertaken at baseline, following the first treatment period, after washout and following the second treatment period. Results: Thirty‐one patients were enrolled. Significant attenuation of clopidogrel’s antiplatelet effects was seen with co‐administration of esomeprazole compared with placebo. Vasodilator stimulated phosphoprotein (VASP), platelet aggregometry (area under the curve (AUC)) and VerifyNow results were 54.7% ± 2.8 platelet reactivity index (PRI), 66.3 ± 2.6 AUC units and 213.1 ± 14.1 platelet reactivity units (PRU) with esomeprazole vs. 47% ± 2.7 PRI, 59.7 ± 3.7 AUC units and 181.4 ± 14.6 PRU with placebo (P < 0.01 esomeprazole vs. placebo for all measures). There was no significant difference in platelet aggregometry (maximal aggregation) between the esomeprazole group (68.9% ± 2.7 units) and placebo‐treated group (64.5% ± 4.1 units; P > 0.05). Conclusion: Esomeprazole when co‐administered with aspirin and clopidogrel results in a significant attenuation of clopidogrel’s antiplatelet effects.     

Study of the Evolution of Masked Bifascicular Block

Masked bifascicular block (MBB) (absent or minimal S in I and VL. high R in V; and ÂQRS approximately -60°) is a rare condition. We have found 16 such cases in the last 12 years, thirteen male and three female, mean age 70 ± 9 years. The conventional electrocardiogram was tabulated and the clinical features and evolution of the patients were followed over 39.1 ± 32 months. Ten patients required pacemakers, nine because of complete atrioventricular (AV) block or increase in the previous AV block. Seven patients died (follow-up 27.3 ± 32 months), five from heart failure. This study shows: (1) MBB is a subgroup of patients with a high risk of advanced atrioventricular block; (2) a pacemaker implant does not significantly reduce the high mortality in this group because of the severity of the underlying disease; (3) these results should be evaluated in a larger series of patients in order to confirm our provisional results.     

Cross-cultural differences in developmental rates: a comparison between British and Brazilian children

The Griffiths Mental Development Scales were administered to a population-based sample of 305 4-year-old children from a Brazilian city. Their performance was compared to that of 285 British children of the same age who participated in the standardization phase of this instrument. Although the mean general quotients were very similar for both groups, British children performed better than Brazilians in the fine motor and practical reasoning scales. Brazilians, on the other hand, proved to be more advanced in gross motor and speech scales. The possibility of these differences being explained in terms of cultural environment is discussed.     

BURNING MOUTH SYNDROME

Background and Objectives. Burning mouth syndrome (BMS) is a frequent process that produces marked oral dysesthetic symptoms. There is controversy over its etiopathogenesis and diagnosis. Therapeutic results are unsatisfactory. The objectives of this study were: (1) to analyze a possible agreement on the definition of BMS; (2) to analyze its cause; (3) to propose a therapeutic scheme that has been shown to be highly effective in our experience and has not been previously reported. Methods. Five hundred patients with symptomatology of BMS were retrospectively evaluated with a study protocol, specially designed for this disease. Patients with local or general disease processes that could cause secondary asymptomatic stomatodynia were excluded from the study. Results. Most of the patients evaluated were women over 60 years of age with oral symptoms, including a sensation of heat and burning, and pain, lasting for months or years, and a history of multiple unsuccessful treatments. The patients showed depression associated with anxiety, with evidence of psychiatric disorders in the family. Based on these findings and eliminating symptomatic painful conditions of the mouth that may simulate this syndrome, we diagnosed a genuine or basic BMS of psychosomatic origin. Therapies used in the treatment of these neurotic conditions were not always useful. Tranylcypromine associated with anxiolytics and hypnotics in low doses plus the support of psychotherapy by the stomatologist were the most effective treatments. Conclusions. The BMS should be defined as a psychosomatic process causing oral dysesthesias for months or years.     

Application of acetamidomethyl and 9-fluorenylmethyl groups for efficient side protection of penicillamine in solid-phase peptide synthesis

Synthesis of S-acetamidomethyl and S-fluorenylmethyl derivatives of penicillamine is described. Both groups are completely stable to all the usual reagents in solid-phase peptide synthesis, including the HF cleavage step, and show an excellent degree of orthogonality to each other. Treatment of the protected peptides Ac-L-Pen(X)-L-Pro-D-Val-L-Cys(X)-NH₂ with thallium (III) trifluoroacetate or iodine for X = Acm or piperidine/DMF (1:1) for X = Fm induced with good yield the formation of the intramolecular disulfide bridge. This cyclic peptide appears to assume a type II β-turn conformation in d₆-DMSO as evidenced by ¹H-NMR spectra.     

Practical approach to solid-phase synthesis of C-terminal peptide amides under mild conditions based on a photolysable anchoring linkage1

Several 3-nitro-4-(N-protected aminomethyl)benzoic acids, with protection provided by tert.-butyloxycar-bonyl (Boc), 9-fluorenylmethyloxycarbonyl (Fmoc), trifluoroacetyl (Tfa), dithiasuccinoyl (Dts), or phthaloyl (Phth), have been prepared by reproducible routes. Synthesis of Dts-handle 6 illustrates some particularly novel and efficient chemistry, and is preferred over more intricate routes to Boc-handle 3 and Fmoc-handle 4. The five handles were each evaluated for their application to the synthesis of peptide amides. Coupling onto amino-functionalized supports provided a general starting point for peptide chain assembly. The handle amino function was deblocked (Boc, Fmoc, Dts), the C-terminal residue was coupled as its N^x-protected free acid, and ultimately the ortho-nitrobenzylamide anchoring linkage was cleaved photolytic-ally to give the corresponding amide. Starting with handles 3, 4, and 6, several free and protected peptide amides were synthesized.     

Acidolytic cleavage of tris(alkoxy)benzylamide (PAL) “internal reference” amino acyl (IRAA) anchoring linkages: validation of accepted procedures in solid-phase peptide synthesis (SPPS)

Under the normal conditions of acidolytic cleavage/deprotection of tris(a1koxy)benzylamide (PAL) anchoring linkages in Fmoc solid-phase peptide synthesis (SPPS), product release occurs by a straightforward single-step pathway. A recently reported cleavage of the NH-VH bond of an amino acyl residue adjacent to PAL [see Int. J. Peptide Protein Res. 38 , 146–153 (1991)] could not be confirmed in novel experiments incorporating a double “internal reference” amino acid (IRAA) design. The results of the present work revalidate the widely accepted application of IRAAs to monitor yields in SPPS, and confirm the reliability of PAL methodology for the preparation of C-terminal peptide amides.