Polatuzumab vedotin to treat relapsed or refractory diffuse large B-cell lymphoma, in combination with bendamustine plus rituximab.

Diffuse large B-cell lymphoma (DLBCL) is the most common non Hodgkin lymphoma (NHL) in adults, and it accounts for about 30% of adult NHL cases. Newly diagnosed patients are treated with rituximab in combination with anthracycline-containing chemotherapy, but a significant number of patients relapse after initial treatment. New strategies for relapsed lymphomas are in development among which antibody-drug conjugates (ADCs) are currently in clinical trials. Polatuzumab vedotin is a novel ADC which binds to the commonly expressed B-cell antigen CD79b, and it delivers monomethyl auristatin E, a small molecule with anti-tubulin activity. Polatuzumab vedotin in combination with bendamustine and rituximab (BR) has been approved in the U.S. and the E.U. for use in patients with relapsed or refractory DLBCL ineligible for transplant. These approvals were based on a randomized study of patients treated with either polatuzumab vedotin plus BR or BR alone, where complete response was 40% in the polatuzumab vedotin + BR group versus 18% in the BR group. The most common adverse events of this treatment were cytopenias and peripheral neuropathy.

Changes in lip 1 year after modified Millard repair.

The aim of this study was to observe changes in the lip 1 year after performing a modified Millard cleft lip repair, by comparing the preoperative and 1-year follow-up appearance of the lip. Twenty-three patients with a unilateral complete cleft were photographed by a standardized method before repair, 7 days after surgery and 12 months after surgery. Lips on the cleft side were measured and compared with the opposite side. Possible results were: equal, longer and shorter. There was no linear correlation between the preoperative and 1-year postoperative appearance of the lip, but there was a linear correlation in lip height between the 7-day and 12-month postoperative results. No matter how severe the initial deformity, primary repair of the cleft lip is crucial in maintaining labial symmetry 1 year after operation.

Electrical characterization of metal-molecule-silicon junctions.

Direct assembly of molecules onto silicon surfaces is of particular interest for potential employment in hybrid organic-semiconductor devices. In the study we report here, aryl diazonium salts were used to assemble covalently bound molecular groups on a hydride-passivated, oxide-free n-type Si(111) surface. The reaction of 4-(trimethylsilylethynyl)benzenediazonium tetrafluoroborate generates a molecular layer of 4-(trimethylsilylethynyl)phenylene (TMS-EP) on the n++-Si(111) surface. The monolayer modifies the electrical properties of the interface and exhibits nonlinear current-voltage characteristics, as compared with the ohmic behavior observed from metal-n++-Si(111) junctions. The result of current-voltage measurements at variable temperatures (from 300 to 10 K) on samples made with the TMS-EP molecule does not show significant thermally-activated transport, indicating that tunneling is the dominant transport mechanism. The measured data is compared to a tunneling model.

Comparison of clarithromycin suspension and amoxycillin syrup for the treatment of children with pharyngitis and/or tonsillitis.

Twenty-three general practices in the UK randomised 229 paediatric patients (aged 1-12 years, body weight > 8 kg) with clinical evidence suggestive of streptococcal tonsillitis and/or pharyngitis in this physician-blind study. Patients received either clarithromycin suspension (7.5 mg/kg twice daily) or amoxycillin syrup (125 mg/kg three times daily body weight < 25 kg, or 250 mg/kg three times daily body weight 25 kg) for 7 days and were followed up 3-8 days post treatment and 21-28 days later. Clinical and microbiological assessments were made at each visit. A total of 189 patients (98 on clarithromycin and 91 on amoxycillin) were clinically evaluable. At the post-treatment visit, clinical success rates were high and comparable: 98% on clarithromycin and 97% on amoxycillin. Streptococcus pyogenes was eradicated in 88% of clarithromycin patients and 86% of amoxycillin patients. Both treatments were well tolerated. In conclusion, clarithromycin suspension was as safe and at least as effective as amoxycillin syrup for the treatment of pharyngitis and/or tonsillitis in children, and would be a suitable alternative therapy.

Serum levels of free 1,25-dihydroxyvitamin D in vitamin D toxicity.

OBJECTIVE: To determine the serum level of free 1,25-dihydroxyvitamin D [1,25-(OH)2D] in patients with vitamin D toxicity and to assess the in vitro effect of differing concentrations of vitamin D metabolites on the free serum levels of 1,25-(OH)2D. DESIGN: 1) A case study of patients hospitalized with vitamin D toxicity after accidentally ingesting a veterinary vitamin D concentrate and 2) an in vitro experiment in which vitamin D metabolites in various concentrations were added to normal serum and their effect was noted on percentage of free 1,25-(OH)2D. PATIENTS: 11 patients (age range, 8 to 69 years) were studied 10 to 40 days after hospitalization for hypercalcemia. MEASUREMENTS: Serum total 25-hydroxyvitamin D (25-OHD) and 1,25-(OH)2D levels were measured by radioreceptor assays. The percentage of free 1,25-(OH)2D was measured by centrifugal ultrafiltration isodialysis and was used to calculate actual free 1,25-(OH)2D levels. In the in vitro studies, vitamin D metabolites [25-OHD; 24,25-(OH)2D; 25,26-(OH)2D; and 25-OHD-26,23 lactone] were added to normal serum in concentrations expected to occur with vitamin D toxicity. The percentage of free 1,25-(OH)2D was measured by isodialysis. RESULTS: All patients presented with marked hypercalcemia (mean calcium level, 3.99 +/- 0.33 mmol/L). Serum 25-OHD levels ranged from 847 to 1652 nmol/L, and total 1,25-(OH)2D levels (mean, 106 +/- 86 pmol/L) were elevated in only three patients. The percentage of free 1,25-(OH)2D (mean, 1.023% +/- 0.366%) was elevated in all nine patients in whom it was measured. Actual free 1,25-(OH)2D levels (mean, 856 +/- 600 fmol/L) were elevated in six of the nine patients. Total 1,25-(OH)2D levels were correlated with 25-OHD levels (r = 0.66; P = 0.03), whereas total and free 1,25-(OH)2D levels were highly correlated (r = 0.957; P < 0.001). In the in vitro studies, the percentage of free 1,25-(OH)2D increased after 25-OHD or 24,25-(OH)2D was added. CONCLUSIONS: Although the patients had normal or near-normal total 1,25-(OH)2D values, most patients had elevated free 1,25-(OH)2D levels. These findings suggest that elevated free 1,25-(OH)2D levels might play a role in the pathogenesis of hypercalcemia in vitamin D toxicity.

Galctopoietic effects of a (1-30)NH2 analog of growth hormone-releasing factor in dairy cows.

Two experiments were conducted to determine the galactopoietic effects of an analog of growth hormone-releasing factor. Specific replacements were made in the AA sequence of growth hormone-releasing factor to produce a growth hormone-releasing factor analog with enhanced stability in vivo. In Experiment 1, 24 Holstein cows were infused i.v. with 0, .33, 1, or 3 mg/d of growth hormone-releasing factor analog for 20 d. Infusion of the analog increased mean serum concentrations of somatotropin, IGF-I, and NEFA. The analog also increased milk yield as much as 44% relative to that of controls. In Experiment 2, 24 Holstein cows were infused i.v. with 0, .11, .33, or 1 mg/d of analog for 60 d. Infusion of analog increased serum concentrations of somatotropin, IGF-I, and NEFA in a dose-dependent manner. At 1 mg/d, the analog increased SCM yield 28% throughout the infusion period relative to the 0 mg/d controls. In summary, a growth hormone-releasing factor analog increased milk yield and serum concentrations of somatotropin and IGF-I. Furthermore, this galactopoietic activity was mediated through the somatotropic axis.

A comparative study of clarithromycin and amoxycillin suspensions in the treatment of pediatric patients with acute otitis media.

This phase III, single-blind, randomized, multicentre clinical trial compared the safety and efficacy of clarithromycin and amoxycillin in the treatment of otitis media in pediatric patients. Two hundred and fifty-nine patients aged 1-12 were prescribed suspensions of clarithromycin (132 patients) or amoxycillin (127 patients). Both suspensions were prescribed at a dose of 125 mg for children weighing less that 25 kg or at 250 mg for children weighing more than 25 kg, but three doses of amoxycillin per day were given, while only two doses clarithromycin per day were required. Each drug was administered for approximately 5 days. Clinical evaluations were performed pre-treatment (Study Day 1), at the end of treatment (Study Days 6-9), and post-treatment (Study Days 28-32). At the end of treatment, 91 out of 114 evaluable patients (80%) had clinical cures with clarithromycin, while 71 out of 105 evaluable patients (68%) had clinical cures with amoxycillin (p = 0.057). Clinical success rates were 96% for both treatments (110/114, clarithromycin; 101/105 amoxycillin). Adverse events related to the study medications occurred in four of 132 patients receiving clarithromycin (3%) and eight out of 127 subjects receiving amoxycillin (6%). Three patients discontinued treatment due to adverse events, all three receiving amoxycillin. At the doses administered, clarithromycin given twice-daily was as safe and effective as given three-times-daily in the treatment of acute otitis media in pediatric patients.

Coronary risk factors in newly diagnosed and previously diagnosed type 2 diabetic men with myocardial infarction.

Risk factors for coronary artery disease in 131 known non-insulin-dependent (type 2) diabetic patients is compared to that in 115 newly diagnosed type 2 diabetic subjects and in 316 non-diabetic patients. The subjects, all Indian men aged 21-60 years, represent consecutive survivors of myocardial infarction and were investigated 3-4 months after their acute episode. A group of 524 healthy Indian men aged 21-60 years were included as controls. Significant differences in parameters measured were noted when all diabetic and non-diabetic patients were compared to the control group. Diabetic patients were older than the non-diabetic patients and with significantly higher frequency of hypertension and hypertriglyceridaemia, whilst smoking and family history of coronary artery disease were elicited more frequently in the non-diabetic patients. Mean concentrations of serum total cholesterol and lipoproteins in the diabetic and non-diabetic men were similar, whereas serum triglyceride concentrations were significantly higher in the diabetic patients. Newly diagnosed and known diabetic patients did not differ with respect to the risk factors examined. Clusters of various combinations of hypertension, obesity, hypertriglyceridaemia and low HDL-cholesterol values were encountered more frequently in diabetic patients when compared to non-diabetic patients, whilst no significant differences were observed when the two groups of diabetic subjects were compared. In conclusion, this study has demonstrated that in men with myocardial infarction there are significant differences between diabetic and non-diabetic patients with respect to certain risk factors. However, newly diagnosed diabetic men have similar risk profiles to their known diabetic counterparts.

Hepatocellular carcinoma in South African Indians resident in Natal.

Hepatoma is a rare disease in Natal Indians. It occurs in male patients in the fifth decade. They have no history of alcohol intake. The main presenting feature is abdominal pain, weight loss and hepatomegaly. Blood tests reveal a raised alkaline phosphatase, hypoalbuminaemia, hypergammaglobulinaemia and markedly raised gamma glutamyl transferase. The tumour is a single large expanding mass in the right lobe. The patient usually presents in a late stage of the illness and shows a progressive downhill course. Hepatitis B virus infection is emerging as the likeliest carcinogen.

Effects of infusions of various doses of bovine growth hormone-releasing factor on blood hormones and metabolites in lactating Holstein cows.

In two experiments, the effects of i.v. infusions of various doses of bovine GH-releasing factor (GRF) on blood hormones and metabolites in lactating Holstein cows were determined. In experiment 1, cows were infused with GRF (0, 3.125, 6.25, 12.5, 25.0 or 50.0 mg/cow per 24 h) for 24 h. Blood was sampled at -1, 5, 11, 15 and 23 h relative to the start of the infusion. The serum concentration of somatomedin C (SM-C) before infusion was 303 +/- 8 (S.E.M.) micrograms/l. Doses of GRF of between 3.125 and 50.0 mg were equipotent in stimulating (P less than 0.05) SM-C by 1.5- to 2.5-fold. GRF-induced increases in SM-C occurred by 11 h from the start of the infusion. In experiment 2, primiparous cows were infused with GRF (0, 1 or 3 mg/24 h) for 20 days. Blood was sampled for 12 h on days 1, 10 and 19. The 1 mg dose of GRF increased (P less than 0.05) blood concentrations of SM-C (on days 10 and 19) and glucose (on day 19), but did not affect blood concentrations of prolactin, insulin, cortisol, tri-iodothyronine (T3), thyroxine (T4), non-esterified fatty acids (NEFA) or glucose. The 3 mg dose of GRF increased (P less than 0.05) blood concentrations of SM-C (on days 10 and 19), T3 (on days 10 and 19), insulin (on day 19), NEFA (on days 1, 10 and 19) and glucose (on day 19), but did not affect blood concentrations of prolactin, cortisol or T4. We conclude that these data are consistent with the hypothesis that the galactopoietic effect of exogenous GRF in dairy cattle is mediated by increased secretion of GH.

Thrombocytosis associated with tuberculous peritonitis.

A young African female is described who showed marked thrombocytosis (platelet count 1372 X 10(9)/l) in association with tuberculous peritonitis, a rare association.