Response to 2'-deoxycoformycin after failure of interferon-alpha in nonsplenectomized patients with hairy cell leukemia

Two patients with hairy cell leukemia with massive splenomegaly and severe pancytopenia were treated with recombinant alpha-A interferon (IFN-alpha-2a). There was no significant response to a trial of IFN- alpha-2a (11 and 20 weeks) with respect to blood counts or spleen size. Subsequent treatment with 2'-deoxycoformycin (dCF) for 8 consecutive weeks (4 mg/m2/wk) resulted in normalization of spleen size and a normalization of peripheral blood counts and bone marrow in one patient. The second patient demonstrated a reduction in spleen size and improved blood counts following 9 weeks of dCF therapy but eventually became refractory. This demonstrates that dCF is non-cross-resistant with interferon and confirms the efficacy of dCF in nonsplenectomized patients.     

Effects of monoclonal antibody therapy in patients with chronic lymphocytic leukemia

A phase I clinical trial was initiated to treat patients with stage IV B-derived chronic lymphocytic leukemia (CLL) with the IgG2a murine monoclonal antibody T101. This antibody binds to a 65,000-mol wt (T65) antigen found on normal T lymphocytes, malignant T lymphocytes, and B- derived CLL cells. All of the patients had a histologically confirmed diagnosis of advanced B-derived CLL and were refractory to standard therapy, and more than 50% of their leukemia cells reacted with the T101 antibody in vitro. The patients received T101 antibody two times per week, over two to 50 hours by intravenous administration in 100 mL of normal saline containing 5% human albumin. Twelve patients were treated with a fixed dosage of 1, 10, 50, or 100 mg, and one patient was treated with 140 mg of antibody. It was demonstrated that patients given two-hour infusions of 50 mg developed pulmonary toxicity, with shortness of breath and chest tightness. This toxicity was eliminated when infusions of 50 or 100 mg of T101 were prolonged to 50 hours. All dose levels caused a rapid but transient decrease in circulating leukemia cell counts. In vivo binding to circulating and bone marrow leukemia cells was demonstrated at all dose levels with increased binding at higher dosages. Antimurine antibody responses were not demonstrated in any patients at any time during treatment. Circulating free murine antibody was demonstrated in the serum of only the two patients treated with 100 mg of antibody as a 50-hour infusion and the patient treated with 140 mg of antibody over 30 hours. Antigenic modulation was demonstrated in patients treated at all dose levels but was particularly apparent in patients treated with prolonged infusions of 50 and 100 mg of antibody. We were also able to demonstrate antigenic modulation in lymph node cells, which strongly suggests in vivo labeling of these cells. Overall, T101 antibody alone appears to have a very limited therapeutic value for patients with CLL. The observations of in vivo labeling of tumor cells, antigenic modulation, antibody pharmacokinetics, toxicity, and antimurine antibody formation may be used in the future for more effective therapy when drugs or toxins are conjugated to the antibody.     

The effect of gender on mental health service use: an examination of mediation through material,social and health-related pathways

Purpose

We aimed to understand how much of the gender difference in mental health service use could be due to the joint mediation of employment, behavioural and material factors, social support and mental health need.

Methods

We used data from employed individuals aged 18–65 years who participated in the 2015–2017 waves of the Household, Income and Labour Dynamics in Australia survey. The exposure (male, female) and confounders were measured in 2015, mediators in 2016 and the outcome—whether a person had seen a mental health professional in the previous year—was measured in 2017. We estimated natural mediation effects using weighted counterfactual predictions from a logistic regression model.

Results

Men were less likely to see a mental health care provider than women. The total causal effect on the risk difference scale was  − 0.045 (95% CI  − 0.056,  − 0,034). The counterfactual of men taking the mediator values of women explained 28% (95% CI 1.7%, 54%) of the total effect, with the natural direct effect estimated to represent an absolute risk difference of  − 0.033 (95% CI  − 0.048,  − 0.018) and the natural indirect effect  − 0.012 (95% CI  − 0.022,  − 0.0027).

Conclusion

Gendered differences in the use of mental health services could be reduced by addressing inequalities in health, employment, material and behavioural factors, and social support.

     

Construct validity of the child abuse potential inventory

In an attempt to provide construct validity for the Child Abuse Potential (CAP) inventory, 176 Ss were given the inventory with its abuse and lie scales, an abbreviated MMPI with ego-strength and lie scales, and the Marlowe-Crowne Social-Desirability (M-C SD) scale. Analysis indicated a significant inverse relationship between the CAP abuse scale and the measure of ego-strength, which indicates that individuals who obtain elevated abuse scores have less adaptability and personal resourcefulness. Significant positive relationships were found between the CAP lie scale and the MMPI lie scale and between the CAP lie scale and the measure of social desirability. However, partial correlations indicated that the MMPI lie scale is relatively more important than social desirability in the understanding of the CAP lie scale. No significant relationships were observed between the CAP lie scale and the measure of ego-strength. Further, no significant relationships were found between the CAP abuse scale and the MMPI lie scale and the CAP abuse scale and the measure of social desirability. The present study provids results that are theoretically consistent with previous research on the CAP inventory.     

Long-term peripheral nerve and muscle recordings from normal and dystrophic mice

A method for long-term recording of electrical activity from small mammalian nerves and muscles is described. Electrodes for stimulating and recording activity were implanted on nerves and muscles subserving ankle flexion and extension in normal and dystrophic mice. Activity was monitored on a regular basis for up to 200 days following implantation. Neural compound action potentials, compound EMG potentials and twitch tension were recorded. Shortly after implantation, evoked EMG and twitch tension declined, but recovered progressively to values measured at the time of implantation and subsequently remained steady in normal mice. However, while dystrophic mice did recover, with EMG levels reaching 50-60% of the values recorded at implantation, tension eventually dropped to 10% in flexor muscles and 25% in extensors.     

Plasticity of autonomic nerves: Differential effects of long-term guanethidine sympathectomy on the sensory innervation of the rat uterus during maturation

The sensory nerves, containing substance P and calcitonin gene-related peptide, and noradrenaline-containing sympathetic nerves of the rat uterus were analyzed following long-term sympathectomy with guanethidine in prepubertal (four weeks), young adult (eight weeks) and fully adult animals (18 weeks). Immunohistochemical and histochemical methods were used in association with nerve density measurements and biochemical assays. The main findings were as follows:

1. (1) long-term guanethidine treatment completely abolished the noradrenergic innervation of the uterine horn and parametrial tissue and markedly reduced the tissue levels of noradrenaline in both regions at the three ages analysed;

2. (2) in the uterine hom guanethidine treatment had no effect on the tissue levels of either calcitonin gene-related peptide or substance P or on the density of calcitonin gene-related peptide-containing nerves, at any of the three ages studied;

3. (3) in the parametrial tissue increased levels of calcitonin gene-related peptide were observed at 8 and 18 weeks of age, together with a significant increase in the density of calcitonin gene-related peptide-containing nerves.

Substance P levels showed a transient increase in this tissue at eight weeks. In conclusion, long-term sympathectomy with guanethidine resulted in an increase in calcitonin gene-related peptide and substance P in sensory nerves in the parametrial tissue, but not in the uterine horn. The changes in the parametrial tissue only occurred after puberty. It is suggested that sensory nerves in the uterine horn may be less responsive to sympathetic denervation since loss of sympathetic nerves occurs as part of a normal physiological process during pregnancy in this region.

前后路联合手术治疗髋臼双柱骨折疗效分析

目的:探讨前后路联合手术治疗髋臼双柱骨折的效果并分析影响疗效的相关因素。方法:2007年8月至2009年7月收治髋臼双柱骨折患者19例,男13例,女6例;年龄27～52岁,平均39.6岁。高位双柱骨折11例,低位双柱骨折8例,双柱骨折累及骶髂关节1例。受伤至手术时间4～11 d,平均5.8 d。患者均采用前后联合入路手术,重建钢板和螺钉内固定。结果:除1例死亡外本组全部获随访,随访时间12～18个月,平均13.6个月。关节功能根据Harris评分标准,术后功能优9例,良7例,可2例。结论:经前后路联合切开复位内固定治疗髋臼双柱骨折疗效满意。     

Prediction and explanation of child abuse

Administered the Child Abuse Potential Inventory to 65 abusing and 65 matched nonabusing parents. An item analysis indicated that 77 of the 160 Inventory items Significantly discriminated between abusers and nonabusers. A discriminant analysis which employed the 77 significant items, correctly classified 125, or 96%, af the 130 Ss as abusers or nonabuser. Identical results were obtained from a stepwise multiple regression analysis. Principal axis factoring with oblique promax rotations yielded a seven-factor solution with relatively specific dimensions. The seven factors, or dimensions, were: Distress, rigidity, child with problem, problem from family and others, unhappiness, loneliness, and negative concept of child and of self. Further analysis revealed that the rigidity, unhappiness, and distress factors were the most meaningful dimensions in the understanding of why some people abuse children.