Effect of omeprazole and cimetidine on duodenal ulcer. A double-blind comparative trial

We conducted a double-blind randomized study of 132 patients to determine whether the new, investigational proton-pump inhibitor, omeprazole (30 mg per day), would accelerate healing and pain relief, as compared with cimetidine (1 g per day), in patients with duodenal ulcer. After two weeks of treatment, which was completed by all patients, the healing rates were 73 per cent in the omeprazole group and 46 per cent in the cimetidine group (P less than 0.01). After four weeks of treatment, which was completed by 118 patients, the corresponding figures were 92 and 74 per cent (P less than 0.05). In the omeprazole group 55 per cent of the patients were free of pain after the first week, as compared with 40 per cent of those treated with cimetidine (P greater than 0.05). No major clinical or biochemical side effects of omeprazole or cimetidine were noted. A six-month follow-up study revealed no significant difference between the recurrence rates after omeprazole and after cimetidine treatment. In May 1984 clinical trials with omeprazole were temporarily suspended, since a study of long-term toxicity in rats had shown the development of gastric carcinoid tumors.     

Genetic alterations of the tumour suppressor gene regions 3p, 11p, 13q, 17p, and 17q in human breast carcinomas.

Fifty-nine primary breast carcinomas and 11 metastases were examined to identify genetic alterations in the tumour suppressor gene regions 3p, 11p, 13q, 17p, and 17q. Loss of heterozygosity (LOH) was frequently observed on chromosome arms 17p (p144D6 lost in 75%, pYNZ22.1 in 55%, and TP53 in 48% of the primary tumours), 13q (RBI lost in 40% of the primary tumours), and 17q (pRMU3 lost in 35%, pTHH59 in 29%, and NM23HI in 26% of the primary tumours). Loss of all the markers except p144D6 was observed even more frequently in the metastases. Pairwise comparisons for concordance of allele losses on 17p indicated that there might be two genes on 17p implicated in breast cancer development; the TP53 gene and a gene located close to the p144D6 and pYNZ22.1 markers. LOH of the RBI gene was associated with LOH of pYNZ22.1 and p144D6, but not with LOH of TP53. LOH of RBI and TP53 was associated with occurrence of ductal carcinomas, RBI and p144D6 losses with tumour size, and p144D6 losses with positive node status as well. LOH of TP53 and the three 17q markers NM23HI, pTHH59, and pRMU3 was most frequently observed in tumours from postmenopausal women. p144D6 losses occurred most frequently in progesterone receptor-negative tumours, whereas pTHH59 losses occurred most frequently in oestrogen receptor-negative tumours. LOH of the investigated loci was not associated with ERBB2 protooncogene amplification, with positive family history of breast cancer, or with survival.     

Recovery of mice from herpes simplex virus type 2 hepatitis: adoptive transfer of recovery with immune spleen cells.

Young BALB/c mice inoculated intraperitoneally with herpes simplex virus type 2 develop focal necrotizing hepatitis. After infection, the livers of these mice show increasing virus titers, which reach a maximum on day 3 after infection; this is followed by a dramatic decrease in the amount of virus recovered on days 4 and 5. This decrease in virus content is accompanied by a progressive infiltration of the lesions with mononuclear leukocytes and an apparent resolution of the lesions. Adoptive transfer of immune spleen cells from mice infected 6 days earlier accelerated this process. When 50 x 10(6) to 100 x 10(6) immune spleen cells were transferred 24 h after infection, the inflammatory response and the clearance of virus from the livers were advanced by almost 2 days. As few as 12 x 10(6) immune spleen cells accelerated the healing process, whereas fewer immune cells, disrupted immune cells, or normal spleen cells did not have an effect. The protection conferred by herpes simplex virus type 2-sensitized immune spleen cells was specific since mouse cytomegalovirus- or vaccinia virus-sensitized immune spleen cells had no effect on the course of infection with herpes simplex virus type 2, whereas some cross-reactivity was observed between herpes simplex virus types 1 and 2. This model seems to be suitable for examining the immunological mechanisms that are active during recovery from visceral herpes simplex virus infections.     

Time interval from human chorionic gonadotrophin (HCG) injection to follicular rupture

The aim of this study was to estimate the time interval fromhuman chorionic gonadotrophin (HCG) injection to follicularrupture. Furthermore, it was observed whether there was anyeffect on the pregnancy rate if the insemination was performedat the time of follicular rupture. In a programme of intrauterineinsemination 37 consecutive cycles in 32 patients were monitoredafter stimulation with clomiphene citrate. HCG was administeredby i.m. injection when a leading follicle of at least 18 mmin diameter was observed sonographically. All patients weremonitored by sonography with 1 h intervals from 32 h after HCGinjection until the first rupture of a follicle. Inseminationwas performed immediately after the first follicular rupture.The pregnancy rate was 16% (5/32). In 66%, the largest folliclewas the first to rupture. The mean time interval from HCG administrationto first follicular rupture was 38.3 h (SEM = 0.54; range =34–16). Our findings support the concept that ovulationoccurs about 38 h after HCG administration. The pregnancy ratewas within the normal range, although insemination was performedat the time of follicular rupture. The largest follicle wasnot always the first to rupture     

Analyses of maximum cardiopulmonary performance during exposure to acute hypoxia at simulated altitude--sea level to 5000 meters (760-404 mm Hg)

The maximum cardiopulmonary performance of seven healthy male subjects was studied repeatedly in graded hypoxia at ambient pressures ranging from 760 to 404 mm Hg (sea level to 5000 m of simulated altitude). Using this approach it has been possible to not only establish a reproducible value for VO2max, but to determine an equation which may be used to predict the VO2 at altitude for healthy, unacclimatized males exercising to exhaustion. Moreover, we have attempted to explain the limits to pulmonary ventilation at decreasing levels of PO2 by comparing a given VO2max (STPD) to the corresponding VEmax (BTPS), showing that any further increase in the latter is impossible when a certain level of altitude has been reached. Finally, our series of experiments indicates that the HRmax falls at altitude. Although statistically significant, this decrement is not conspicuous. Thus, when used with the VO2max to calculate the number of ml of O2 consumed per beat of the heart, the "oxygen pulse" turns out to be more sensitive to the fall in VO2max at altitude than to the corresponding decrease in the HRmax.     

Boric acid single dose pharmacokinetics after intravenous administration to man

Eighth young adult male volunteers with a basic (alimentary) plasma boric acid concentration of <0.10–0.46 mg/l were given a single dose of boric acid (562–611 mg) by 20 min IV infusion. The plasma concentration curves, followed for 3 days, best fitted a three-compartment open model, although two subjects had to be left out due to inconstant basal plasma concentration values or failure to fit to the three-compartment model. The 120 h urinary excretion was 98.7±9.1% of dose, Cl_tot 54.6±8.0 ml/min/1.73 m², t_1/2 21.0±4.9 h and distribution volumes V₁, V₂, and V₃: 0.251±0.099, 0.456±0.067 and 0.340±0.128 l/kg.     

Disaggregating proportional multistate lifetables by population heterogeneity to estimate intervention impacts on inequalities

The mortality pattern from birth to age five is known to vary by underlying cause of mortality, which has been documented in multiple instances. Many countries without high functioning vital registration systems could benefit from estimates of age- and cause-specific mortality to inform health programming, however, to date the causes of under-five death have only been described for broad age categories such as for neonates (0–27 days), infants (0–11 months), and children age 12–59 months. We adapt the log quadratic model to mortality patterns for children under five to all-cause child mortality and then to age- and cause-specific mortality (U5ACSM). We apply these methods to empirical sample registration system mortality data in China from 1996 to 2015. Based on these empirical data, we simulate probabilities of mortality in the case when the true relationships between age and mortality by cause are known. We estimate U5ACSM within 0.1–0.7 deaths per 1000 livebirths in hold out strata for life tables constructed from the China sample registration system, representing considerable improvement compared to an error of 1.2 per 1000 livebirths using a standard approach. This improved prediction error for U5ACSM is consistently demonstrated for all-cause as well as pneumonia- and injury-specific mortality. We also consistently identified cause-specific mortality patterns in simulated mortality scenarios. The log quadratic model is a significant improvement over the standard approach for deriving U5ACSM based on both simulation and empirical results.     

Early Identification of Patient Satisfaction Two Years After Total Knee Arthroplasty

BackgroundThere are numerous reports of poor satisfaction after total knee arthroplasty (TKA), yet there is little known about when to use evidence-based models of care to improve patient outcomes.ObjectiveThis study aimed to characterize longitudinal changes in patient-reported satisfaction after TKA and to identify factors for early identification of poor satisfaction.MethodsFor a cohort of primary TKA surgeries (n = 86), patient-reported outcomes were captured one week before TKA and 6 weeks, 12 weeks, 6 months, and 1 and 2 years after TKA. “Satisfied” versus “not fully satisfied” patients were defined using a binary response (≥90 vs <90) from a 100-point scale. Wilcoxon signed-rank tests identified changes in satisfaction between follow-up times, and longitudinal analyses examined demographic and questionnaire factors associated with satisfaction.ResultsImprovements in satisfaction occurred within the first 6 months after TKA (P ≤ 0.01). Preoperative patient-reported outcome measures alone were not predictive of satisfaction. Key factors that improved longitudinal satisfaction included higher Oxford Knee Scores (odds ratio (OR) = 2.1, P < .001), general health (EQ-VAS, OR = 1.3, P = .03), and less visual analog scale pain (VAS; OR = 1.7, P < .001). Differences in these factors between satisfied and not fully satisfied patients were identified as early as 6 weeks after surgery.ConclusionVisibly different satisfaction profiles were captured among satisfied and not fully satisfied patient responses, with differences in patient-perceived joint function, general health, and pain severity occurring as early as 6 weeks after surgery. This study provides metrics to support early identification of patients at risk of poor TKA satisfaction, enabling clinicians to apply timely targeted treatment and support interventions, with the aim of improving patient outcomes.