Acupuncture point injection treatment of primary dysmenorrhoea: a randomised, double blind, controlled study.

OBJECTIVE: To determine if injection of vitamin K3 in an acupuncture point is optimal for the treatment of primary dysmenorrhoea, when compared with 2 other injection treatments. SETTING: A Menstrual Disorder Centre at a public hospital in Shanghai, China. PARTICIPANTS: Chinese women aged 14-25 years with severe primary dysmenorrhoea for at least 6 months not relieved by any other treatment were recruited. Exclusion criteria were the use of oral contraceptives, intrauterine devices or anticoagulant drugs, pregnancy, history of abdominal surgery, participation in other therapies for pain and diagnosis of secondary dysmenorrhoea. Eighty patients with primary dysmenorrhoea, as defined on a 4-grade scale, completed the study. Two patients withdrew after randomisation. INTERVENTIONS: A double-blind, double-dummy, randomised controlled trial compared vitamin K3 acupuncture point injection to saline acupuncture point injection and vitamin K3 deep muscle injection. Patients in each group received 3 injections at a single treatment visit. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome was the difference in subjective perception of pain as measured by an 11 unit Numeric Rating Scale (NRS). Secondary measurements were Cox Pain Intensity and Duration scales and the consumption of analgesic tablets before and after treatment and during 6 following cycles. RESULTS: Patients in all 3 groups experienced pain relief from the injection treatments. Differences in NRS measured mean pain scores between the 2 active control groups were less than 1 unit (-0.71, CI -1.37 to -0.05) and not significant, but the differences in average scores between the treatment hypothesised to be optimal and both active control groups (1.11, CI 0.45 to 1.78) and (1.82, CI 1.45 to 2.49) were statistically significant in adjusted mixed-effects models. Menstrual distress and use of analgesics were diminished for 6 months post-treatment. CONCLUSIONS: Acupuncture point injection of vitamin K3 relieves menstrual pain rapidly and is a useful treatment in an urban outpatient clinic. TRIAL REGISTRATION NUMBER: NCT00104546; Results.

Disclosure of complementary health approaches among low income and racially diverse safety net patients with diabetes.

OBJECTIVE: Patient-provider communication about complementary health approaches can support diabetes self-management by minimizing risk and optimizing care. We sought to identify sociodemographic and communication factors associated with disclosure of complementary health approaches to providers by low-income patients with diabetes. METHODS: We used data from San Francisco Health Plan's SMARTSteps Program, a trial of diabetes self-management support for low-income patients (n=278) through multilingual automated telephone support. Interviews collected use and disclosure of complementary health approaches in the prior month, patient-physician language concordance, and quality of communication. RESULTS: Among racially, linguistically diverse participants, half (47.8%) reported using complementary health practices (n=133), of whom 55.3% disclosed use to providers. Age, sex, race/ethnicity, nativity, education, income, and health literacy were not associated with disclosure. In adjusted analyses, disclosure was associated with language concordance (AOR=2.21, 95% CI: 1.05, 4.67), physicians' interpersonal communication scores (AOR=1.50, 95% CI: 1.03, 2.19), shared decision making (AOR=1.74, 95% CI: 1.33, 2.29), and explanatory-type communication (AOR=1.46, 95% CI: 1.03, 2.09). CONCLUSION: Safety net patients with diabetes commonly use complementary health approaches and disclose to providers with higher patient-rated quality of communication. PRACTICE IMPLICATIONS: Patient-provider language concordance and patient-centered communication can facilitate disclosure of complementary health approaches.

Long-term outcomes of patients with localized rectal cancer treated with chemoradiation or radiotherapy alone because of medical inoperability or patient refusal.

PURPOSE: The standard management of rectal cancer continues to be defined by the results of randomized, clinical trials exploring the optimal timing and use of adjuvant chemotherapy and radiation therapy in relation to surgery. The patient with rectal cancer who is elderly and/or has significant comorbidities and the patient who refuses surgery are clinical contexts for which there is limited current data to guide decision making. METHODS: A retrospective analysis was performed at six Australian centers of patients with rectal cancer treated with radiation therapy or chemoradiation alone because of excessive operative risk or patient refusal of surgery. RESULTS: We identified 48 patients treated between August 1998 and June 2005 with a median age of 76 (range, 49-94) years. Twenty-four patients (50 percent) were considered medically inoperable and 24 patients refused surgery. Treatment was with chemoradiation (with 5-fluorouracil) in 36 patients and radiotherapy alone in 12 patients; 93 percent completed the planned therapy. A clinical complete response was seen in 56 percent and a partial response in 30 percent of patients. At a median follow-up of 49 months, 18 patients have disease progression, including 10 of 24 in the medically inoperable group and 8 of 24 in the refused surgery group. Of the 25 deceased patients, 16 died from progressive disease and 9 from noncancer causes. CONCLUSIONS: Chemoradiation or radiotherapy alone is a safe alternative that results in significant progression-free and overall survival times in patients who are considered medically inoperable or refuse to undergo surgery. Ultimately, however, many patients will progress.

Identification of a zinc finger protein whose subcellular distribution is regulated by serum and nerve growth factor.

A subclass of zinc finger proteins containing a unique protein motif called the positive regulatory (PR) domain has been described. The members include the PRDI-BF1/Blimp-1 protein, the Caenorhabditis elegans egl-43 and EVI1 gene products, and the retinoblastoma interacting protein RIZ. Here we describe a member of this family, SC-1, that exhibits several distinctive features. First, SC-1 interacts with the p75 neurotrophin receptor and is redistributed from the cytoplasm to the nucleus after nerve growth factor (NGF) treatment of transfected COS cells. The translocation of SC-1 to the nucleus was specific for p75, as NGF binding to the TrkA receptor did not lead to nuclear localization of SC-1. Thus, SC-1 provides a downstream transducer for the effects of NGF through the p75 neurotrophin receptor. Under normal growth conditions, SC-1 was found predominantly in the cytoplasm. On serum-starvation, SC-1 also translocated into the nucleus. A direct correlation between nuclear expression of SC-1 with the loss of BrdUrd incorporation was observed. These results imply that SC-1 may be involved in events associated with growth arrest.

Neuroprotection in relation to retinal ischemia and relevance to glaucoma.

Management of glaucoma is directed at the control of intraocular pressure (IOP), yet it is recognized now that increased IOP isjust an important risk factor in glaucoma. Therapy that prevents the death of ganglion cells is the main goal of treatment, but an understanding of the causes of ganglion cell death and precisely how it occurs remains speculative. Present information supports the working hypothesis that ganglion cell death may result from a particular form of ischemia. Support for this view comes from the fact that not all types of retinal ischemia lead to the pathologic findings seen in glaucomatous retinas or to cupping in the optic disk area. Moreover, in animal experiments in which ischemia is caused by elevated IOP, a retinal abnormality similar to that seen in true glaucoma is produced, whereas after occlusion of the carotid arteries a different pattern of damage is found. In ischemia, glutamate is released, and this initiates the death of neurons that contain ionotropic glutamate (NMDA) receptors. Elevated glutamate levels exist in the vitreous humor of patients with glaucoma, and NMDA receptors exist on ganglion cells and a subset of amacrine cells. Experimental studies have shown that a variety of agents can be used to prevent the death of retinal neurons (particularly ganglion cells) induced by ischemia. These agents are generally those that block NMDA receptors to prevent the action of the released glutamate or substances that interfere with the subsequent cycle of events that lead to cell death. The major causes of cell death after activation of NMDA receptors are the influx of calcium into cells and the generation of free radicals. Substances that prevent this cascade of events are, therefore, often found to act as neuroprotective agents. For a substance to have a role as a neuroprotective agent in glaucoma, it would ideally be delivered topically to the eye and used repeatedly. It is, therefore, of interest that betaxolol, a beta-blocker presently used to reduce IOP in humans, also has calcium channel-blocking functions. Moreover, experimental studies show that betaxolol is an efficient neuro protective agent against retinal ischemia in animals, when injected directly into the eye or intraperitoneally.

Inhibition of protein kinase C translocation from cytosol to membrane by chelerythrine.

Protein kinase C (PKC) is regarded as an important signal in cellular responses. Chelerythrine, the alkaloid in Zanthoxylum simulans, was recently introduced as a specific blocker of PKC phosphorylation. The present study demonstrated an inhibitory effect of chelerythrine on the translocation of PKC from cytosol to membrane using Western blotting analysis. An increase of PKC translocation from cytosol to the membrane was observed in isolated ileal synaptosomes incubated with phorbol 12-myristate 13-acetate (PMA) to reach the plateau at 30 min later. Pretreatment with chelerythrine for 20 min attenuated this action of PMA in a concentration-dependent manner and the inhibition of PKC alpha translocation was similar to that of PKC beta. An inhibitory effect of chelerythrine on the translocation of PKC is considered in addition to the inhibition of PKC phosphorylation.

Cleidocranial dysplasia: a rare case associated with congenital hypothyroidism and severe neonatal hyperbilirubinemia.

Cleidocranial dysplasia is an autosomal dominant disorder affecting skeletal ossification and tooth development. This disorder can be rarely associated with blood, intestinal and vascular anomalies. There has been no case reported in previous literature that discusses this disorder in association with congenital hypothyroidism and severe neonatal hyperbilirubinemia. Herein, we report on a 4-year-old boy who in an outpatient clinic was diagnosed as having cleidocranial dysplasia, with defective ossification over bilateral hypoplastic clavicles, narrowed thoracic cage on chest x-ray and prominent wormian bones over the lambdoid sutures on skull x-ray. Physical examination revealed a 4-fb wide open anterial fontanel, frontal bossing and malalignment of teeth. He was a primpara with birth weight of 2350 gm and gestation age of 33 weeks. He had received blood exchange transfusion on the 4th postnatal day at Ping-Tong Christian Hospital because of severe neonatal hyperbilirubinemia. Congenital hypothyroidism was diagnosed on the 10th day. He was then treated with thyroxine and transferred to our hospital. Thyroid scan revealed diffusely decreased radioactivity in bilateral lobes of the thyroid gland. According to out clinic findings at his regular follow ups, with continued use of thyroxine supplement, he now has a normal thyroid function and has a body length of about 50 percentile.

Postoperative adjuvant radiotherapy and 5-fluorouracil chemotherapy for rectal carcinoma.

Postoperative combined modality therapy with radiotherapy and 5-fluorouracil (5FU) chemotherapy is an effective adjuvant approach that reduces locoregional and distant metastatic disease in patients with high-risk rectal carcinoma. However, this approach results in a treatment regimen of at least 6 months' duration. The present prospective study investigates the integration of radiotherapy and 5FU chemotherapy in a protocol designed to minimize toxicity and reduce the overall treatment time. A total of 40 patients with TNM stage II or III disease received postoperative radiotherapy at four fractions per week with weekly 5FU bolus injections delivered on the fifth non-radiotherapy day. Patients also received systemic chemotherapy with leucovorin both before and after pelvic irradiation, with the total treatment duration extending for only 18 weeks. Patients were able to complete radiotherapy in 90% of cases, while the delivery of full-dose chemotherapy was achievable in the vast majority. The incidence of haematologic and gastrointestinal toxicities requiring the cessation of treatment was acceptable. With a median follow-up of 20.9 months among surviving patients, the estimated progression-free and overall survival at 2 years were 71% and 79%, respectively.

A cytoplasmic tyrosine is essential for the basolateral localization of mutants of the human nerve growth factor receptor in Madin-Darby canine kidney cells.

Deletion of 58 internal amino acids from the C-terminal cytoplasmic domain of p75 human nerve growth factor receptor (hNGFR) changes its localization from apical to basolateral in transfected Madin-Darby Canine Kidney (MDCK) cells (Le Bivic, A., Sambuy, Y., Patzak, A., Patil, N., Chao, M., and Rodriguez-Boulan, E. (1991) J. Cell Biol. 115, 607-618). The mutant protein, PS-NGFR, also shows a dramatic increase in its ability to endocytose NGF and to recycle through basolateral endosomes. We report here the site-directed mutagenesis analysis of PS-NGFR to localize and characterize its basolateral and endocytic sorting signals. Both signals reside in the proximal part of the PS cytoplasmic tail, between positions 306 and 314. Transferring the cytoplasmic tail (19 residues) and transmembrane domain of a truncated PS mutant to the ectodomain of the placental alkaline phosphatase, an apical glypiated ectoenzyme, redirected it to the basolateral membrane and the endocytic compartments. A tyrosine at position 308, present in this short cytoplasmic segment, was mutated into phenylalanine or alanine. The resulting mutants were expressed predominantly on the apical membrane of MDCK cells. Their ability to endocytose NGF was reduced with the alanine mutant showing the stronger diminution. The PS mutant contains a short cytoplasmic sequence necessary both for basolateral targeting and endocytosis, and the requirement for tyrosine at position 308 is crucial for basolateral targeting.

Analysis of the trk NGF receptor tyrosine kinase using recombinant fusion proteins.

Nerve growth factor (NGF) represents a family of structurally related trophic factors, including brain-derived neurotrophin factor (BDNF), neurotrophin-3 (NT-3), NT-4, and NT-5. These neurotrophin factors interact with two classes of receptors, the trk receptor tyrosine kinase family, and the low affinity p75 neurotrophin receptor. To study potential ligand-receptor interactions, recombinant trk fusion proteins have been constructed, and pan-trk polyclonal antisera directed against the cytoplasmic tyrosine kinase domain have been generated. The recombinant proteins were assessed for in vitro kinase activity and for the ability of K-252a to inhibit phosphorylation. Antibodies made against the fusion protein recognize all trk family members, and are effective in immunoprecipitation of affinity-crosslinked receptors. Comparative crosslinking indicates that NGF can recognize all trk receptor members, illustrating the large number of potential ligand-receptor interactions between neurotrophins and their receptors.