Lymphocyte subpopulations in multiple sclerosis: serial studies and clinical correlations.

Total lymphocyte counts and T and SIg+ cell numbers in peripheral blood were determined in 74 healthy controls and 44 MS patients. Twenty-five patients were studied in relapse and at two intervals after ACTH. Nineteen had not relapsed for 6 months but most had progressed clinically. MS patients showed significantly lower total lymphocyte counts which were not correlated with disease activity. Subpopulation analyses showed the MS patients to have significantly lower T cell numbers and significantly elevated SIg+ cell numbers and percentages. Although T cell numbers were low in all phases, both T and SIg+ cell abnormalities were maximal in progressive disease or in the recovery phase after relapse and a significant fall in T cell percentage and rise in SIg+ cell number was confirmed in serial studies of 16 patients followed from relapse to recovery. SIg+ cell numbers correlated negatively with relapse rate and correlated positively with the ratio of disability to number of relapses. The incidence in MS patients of HLA A3 was significantly increased and of HLA B12 and HLA BW40 significantly decreased but no correlation was seen between HLA phenotype and T, SIg+ or total lymphocyte counts. It is suggested that the peripheral blood SIg+ cell abnormalities and some of the T cell abnormalities are secondary to the pathological process, perhaps due to antigenic stimulation and particularly in non-relapsing progressive disease. Their possible role in influencing recovery or progression is discussed.     

Emergency treatment of variceal haemorrhage.

For the initial control of haemorrhage from oesophageal varices, two methods of vasopressin administration have been compared--the conventional bolus of 20 units and a low dose infusion of 0.4 units per minute. Twenty patients bleeding from oesophageal varices, confirmed by endoscopy, were allocated into either treatment group (10 in each). Vasopressin infusion stopped bleeding in 86 per cent of the episodes in contrast to 12.5 per cent (P less than 0.01) with bolus doses. Balloon tamponade with a Sengstaken-Blakemore tube was used to control bleeding in only 2 episodes in patients on infusion and in 10 episodes in patients on bolus doses of vasopressin (P less than 0.05). Our study confirms that low dose vasopressin infusion in more effective in controlling bleeding from oesophageal varices than conventional bolus doses.     

Opportunities to Fast-Track Chinese Herbal Therapies into Clinical Practice Through Research Networks

Chinese herbal therapies provide new opportunities to treat cancer and reduce adverse events at multiple chemical,molecular, and physiological levels. Chinese medicine incorporates the notion of ＇biosemiosis.＇ This emphasizes biology considered from the perspectives of signs conveyed and interpreted in a variety of ways,through systems at the macroscopic and microscopic levels, including the communication of singns and meaning between molecules. It respects the complexity of living processes and incorporates digital and analogue information, reductionism, holism, objectivity, and subjectivity into one system that can be approached scientifically. It attempts to bring together separate findings of the various disciplines of biology into a new and more unified perspective including the generation of systems and function in living organisms. The study of Chinese herbal therapies within the context of Western biomedicine requires a biosemiotic approach that extends research into a complex network that emerges as a virtyal laboratory.     

Late solitary skeletal metastasis to the patella from retinoblastoma

Isolate metastasis to the patella is rare. A young girl treated with bilateral enucleation for retinoblastoma, reported 9 years later with solitary patellar metastasis. Treatment options for distant metastasis from retinoblastoma are not well defined but include combinations of chemotherapy, radiotherapy and surgery. Late skeletal metastasis from retinoblastoma should be differentiated from second primary bone malignancies, with immunohistochemistry, cytogenetic and electron microscopic features, as the prognosis and management are different.     

Daratumumab With Cetrelimab,an Anti–PD-1 Monoclonal Antibody,in Relapsed/Refractory Multiple Myeloma

BackgroundDaratumumab is approved for relapsed or refractory multiple myeloma (RRMM) as monotherapy or in combination regimens. We evaluated daratumumab plus cetrelimab, a programmed death receptor-1 inhibitor, in RRMM.Patients and MethodsThis open-label, multiphase study enrolled adults with RRMM with ≥ 3 prior lines of therapy. Part 1 was a safety run-in phase examining dose-limiting toxicities of daratumumab (16 mg/kg intravenously weekly for cycles 1-2, biweekly for cycles 3-6, and monthly thereafter) plus cetrelimab (240 mg intravenously biweekly, all cycles). In Parts 2 and 3, patients were to be randomized to daratumumab with or without cetrelimab (same schedule as Part 1). Endpoints included safety, overall response rate, pharmacokinetics, and biomarker analyses.ResultsNine patients received daratumumab plus cetrelimab in the safety run-in, and 1 received daratumumab in Part 2 before administrative study termination following a data monitoring committee’s global recommendation to stop any trial including daratumumab combined with inhibitors of programmed death receptor-1 or its ligand (programmed death-ligand 1). The median follow-up times were 6.7 months (safety run-in) and 0.3 months (Part 2). No dose-limiting toxicities occurred. All 10 patients had ≥ 1 treatment-emergent adverse event; 7 patients had grade 3 to 4 treatment-emergent adverse events, and none led to treatment discontinuation or death. In the safety run-in, 7 (77.7%) patients had ≥ 1 infusion-related reaction (most grade 1-2), and 1 had a grade 2 immune-mediated reaction. Among safety run-in patients, the overall response rate was 44.4%.ConclusionsNo new safety concerns were identified for daratumumab plus cetrelimab in RRMM. The short study duration and small population limit complete analysis of this combination.     

Idiopathic thrombocytopenic purpura and its fundus features in a patient with diabetes mellitus

In this case report, we present a patient with thrombocytopenia secondary to idiopathic thrombocytopenic purpura (ITP), whose fundus appearance had features of diabetic retinopathy with macular edema. The macular edema did not respond to multiple intravitreal Anti-Vascular endothelial growth factor (Anti-VEGF), contrary to diabetic cystoid macular edema (CME). He was systemically investigated and was found to have ITP, and its management resulted in complete regression of the hemorrhages and CME.     

Clostridium difficile colitis that fails conventional metronidazole therapy: response to nitazoxanide

OBJECTIVES: Clostridium difficile-associated disease has increased in incidence and severity. Recommended treatments include metronidazole and vancomycin. Recent investigations, however, document the failure of metronidazole to cure a substantial proportion of patients with Clostridium difficile colitis, but oral administration of vancomycin raises concerns over selection of antibiotic-resistant organisms in the hospital environment. We have recently shown that nitazoxanide is as effective as metronidazole in initial therapy for C. difficile colitis. We hypothesized that this drug might be effective in treating patients who fail therapy with metronidazole. METHODS: In the present study, we identified 35 patients who failed treatment with metronidazole for C. difficile colitis; failure was defined as either no improvement in symptoms or signs of disease (28 patients) after >or= 14 days of treatment with metronidazole or prompt recurrence on at least two occasions after initially responding to such treatment (seven patients). These patients were ill with numerous co-morbidities. Nitazoxanide, 500 mg twice daily, was given for 10 days; results from all patients are included. RESULTS: Twenty-six (74%) of 35 patients responded to nitazoxanide, of whom seven later had recurrent disease, yielding a cure rate of 19 of 35 (54%) from initial therapy. Three who initially failed and one who had recurrent disease were re-treated with, and responded to, nitazoxanide. Thus, the aggregate cure with nitazoxanide in this difficult-to-treat population was 23 of 35 (66%). CONCLUSIONS: Nitazoxanide appears to provide effective therapy for patients with C. difficile colitis who fail treatment with metronidazole.     

Enhancement of air-stability, π-stacking ability,and charge transport properties of fluoroalkyl side chain engineered n-type naphthalene tetracarboxylic diimide compounds

In this study, the impact of fluoroalkyl side chain substitution on the air-stability, π-stacking ability, and charge transport properties of the versatile acceptor moiety naphthalene tetracarboxylic diimide (NDI) has been explored. A density functional theory (DFT) study has been carried out for a series of 24 compounds having different side chains (alkyl, fluoroalkyl) through the imide nitrogen position of NDI moiety. The fluoroalkyl side chain engineered NDI compounds have much deeper highest occupied molecular orbitals (HOMO) and lowest unoccupied molecular orbitals (LUMO) than those of their alkyl substituted compounds due to the electron withdrawing nature of fluoroalkyl groups. The higher electron affinity (EA > 2.8 eV) and low-lying LUMO levels (<−4.00 eV) for fluoroalkyl substituted NDIs reveal that they may exhibit better air-stability with superior n-type character. The computed optical absorption spectra (∼386 nm) for all the investigated NDIs using time-dependent DFT (TD-DFT) lie in the ultra-violet (UV) region of the solar spectrum. In addition, the low value of the LOLIPOP (Localized Orbital Locator Integrated Pi Over Plane) index for fluoroalkyl side chain comprising NDI compounds indicates better π–π stacking ability. This is also in good agreement for the predicted π–π stacking interaction obtained from a molecular electrostatic potential energy surface (ESP) study. The π–π stacking is thought to be of cofacial interaction for the fluoroalkyl substituted compounds and herringbone interaction for the alkyl substituted compounds. The calculated results shed light on why side chain engineering with fluoroalkyl groups can effectively lead to better air-stability, π-stacking ability and improved charge transport properties.

In this study, the impact of fluoroalkyl side chain substitution on the air-stability, π-stacking ability, and charge transport properties of the versatile acceptor moiety naphthalene tetracarboxylic diimide (NDI) has been explored.