Bone mineral density changes after parathyroidectomy are dependent on biochemical profile

Background

Bone mineral density (BMD) has been found to improve after parathyroidectomy (PTX) in patients with primary hyperparathyroidism. There are few data on the effect of PTX on BMD in normocalcemic and normohormonal primary hyperparathyroidism.

Antenatal card for illiterate traditional birth attendants

The training and use of trained birth attendants (TBAs) in Guinea Bissau was started in 1977 as part of the primary health care program. The majority of TBAs are illiterate, making accurate record-keeping of antenatal visits ineffective. This paper presents an antenatal card developed by the Ministry of Health and Social Affairs in use since 1982. The card was designed for several purposes: to help nurse-supervisors find and correct mistakes, to help TBAs remember what to look for during antenatal visits, and to enable them to identify at-risk pregnancies and refer them if necessary. The card requires no writing other than the initial visit, when it is suggested that a literate person assist the TBA in recording name, age, and village. Pictorial symbols are used on the rest of the card, which is retained by the patient between visits. The card is divided into 3 areas: a history (number of live children, number of dead children, number of abortions) recorded by placing the correct number of ticks in the proper column; examination (weight if possible, signs of anemia and edema indicated by a +or-, height of uterus, presence of fetal heart sounds); care (reminding TBAs to give nutritional advice, malaria prophylaxis, dispense iron tablets, determine if referral is necessary). The card needs to be field tested by nurses and midwives who will be training the TBAs, and then evaluated for its use in detecting at-risk pregnancies, making any additions or changes as necessary.     

Long-term results and complications of preoperative radiation in the treatment of rectal cancer

A retrospective study of 149 patients with rectal cancer diagnosed between 1972 and 1979 was undertaken to compare survival, disease-free survival, recurrence sites, and long-term complications of 40 patients who received 4000 to 4500 rads of preoperative adjuvant radiotherapy (radiation group) with those of 109 patients treated by resection alone (control group). After a mean follow-up of 84 months and 99 months, respectively, survival of the irradiated patients was significantly better than that of controls (68% versus 52%, p less than 0.05). Disease-free survival of those patients rendered free of disease by treatment was also superior for the irradiated group (84% versus 57%, p less than 0.005). Local recurrence without signs of distant metastases developed only one-third as often in irradiated patients (6% versus 18%). Distant metastases, alone or in combination with local recurrence, were also less common after radiation (12% versus 27%). Second primary tumors developed in 15% and 10% of the respective groups, a difference that was not statistically significant. When we consider the survival benefit of preoperative radiation therapy, long-term complications were relatively mild. Delayed healing of the perineum was noted in two irradiated patients. Persistent diarrhea was severe enough to warrant treatment in only one case, and one patient required a colostomy for intestinal obstruction from pelvic fibrosis.     

Thymidylate synthase activity,folates, and glutathione system in head and neck carcinoma and adjacent tissues

Background. Head and neck squamous cell carcinomas (HNSCC) present variable aggressiveness and chemosensitivity. Because the glutathione (GSH) system and thymidylate synthase (TS) are involved in the resistance to the main drugs used in HNSCC (cisplatin and 5-FU), we studied these systems in tumors and normal mucosae. Methods. Tumor samples and normal adjacent mucosae were collected from 37 untreated HNSCC patients. GSH and glutathione S-transferase (GST) activity were assayed by spectrophotometry, whereas TS activity and folates were determined by radioassays. Results. Mean GSH levels were higher in tumors (15.2 ± 8.2 nmol/mg protein) than in mucosae (8.3 ± 4.1 nmol/mg protein) (p = 0.005, paired t test). GST activity was also higher in tumors (394 ± 194 nmol/min/mg protein) than in mucosae (261 ± 132 nmol/min/mg protein) (p = 0.0003). TS activity was markedly higher in tumors (9.2 ± 21.5 pmol/min/mg protein) compared to that of mucosae (0.9 ± 1.2 pmol/min/mg protein) (p = 0.0001). Folate levels in tumors and mucosae were similar (1.2 ± 1.1 and 0.8 ± 0.9 pmol/mg protein, respectively; p = 0.1, NS). In relation to clinical stage and tumor size, a statistical difference was found in GSH and GST values between tumors and mucosae for stage IV and T3/T4. The increase in tumor TS compared to that of mucosae was significant for all clinical stages, tumor sizes, and nodal involvement. Conclusions. These data enhance our understanding of the enzymatic systems involved in cisplatin and 5-fluorouracil (5-FU) resistance in HNSCC and normal mucosae and may help to elucidate tumor behavior and interpatient differences in drug sensitivity. © 1994 John Wiley & Sons, Inc.     

Flavone acetic acid (LM-975; NSC-347512) activation to cytotoxic species in vivo and in vitro

Summary Flavone acetic acid (FAA; LM 975; NSC 347512) is a new anticancer agent with unprecedented, broad antitumor activity in murine models. Although FAA is very effective in vivo against solid tumors, including colon 38 adenocarcinoma, it was not cytotoxic in vitro against colon 38 cells and human colon adenocarcinoma cells HCT116 at pharmacologically achievable concentrations and exposure times. For example, a concentration of 300 g/ml for a 10-day exposure time was required to obtain <1log cell kill. After the administration of an effective FAA dose (180 mg/kg, i.v.) to mice, plasma cytotoxicity against HCT116 cells attained a 2 log cell kill between 0.5 and 2 h, which decreased to 1 log cell kill at 4 h. No cytotoxicity was observed 6, 12 or 21 h after drug administration. The controls used comprised mouse plasma containing FAA concentrations similar to those assayed in the above plasma samples from in-vivo-dosed mice. These apiked plasma were not cytotoxic, indicating that other cytotoxic species, formed in vivo, were responsible for the increased cytotoxicity. Mouse hepatocytes co-cultured with HCT116 cells increased FAA cytotoxicity to 1 log cell kill at 30–100 g/ml. The addition of phenobarbital-induced mouse liver supernatant S-9000xg also markedly increased FAA cytotoxicity to a 2 log cell kill at 300 g/ml. We conclude that FAA can be activated both in vivo and in vitro to cytotoxic species that are more active than the parent compound.Part of this work has been published in abstract form in: Proc Am Assoc Cancer Res 29: 484, 1988     

Gene conversion is a likely cause of mutation in PKD1

Approximately 70% of the gene responsible for the most common form of autosomal dominant polycystic kidney disease ( PKD1 ) is replicated in several highly homologous copies located more proximally on chromosome 16. We recently have described a novel technique for mutation detection in the duplicated region of PKD1 that circumvents the difficulties posed by these homologs. We have used this method to identify two patients with a nearly identical cluster of base pair substitutions in exon 23. Since pseudogenes are known to be reservoirs for mutation via gene conversion events for a number of other diseases, we decided to test whether these sequence differences in PKD1 could have arisen as a result of this mechanism. Using changes in restriction digest patterns, we were able to show that these sequence substitutions are also present in N23HA, a rodent-human somatic cell hybrid that contains only the PKD1 homologs. Moreover, these changes were also detected in total DNA from several affected and unaffected individuals that did not harbor this mutation in their PKD1 gene copy. This is the first example of gene conversion in PKD1 , and our findings highlight the importance of using gene-specific reagents in defining PKD1 mutations.      

Subcortical auditory input to the primary visual cortex in anophthalmic mice

Anatomical and imaging studies show ample evidence for auditory activation of the visual cortex following early onset of blindness in both humans and animal models. Anatomical studies in animal models of early blindness clearly show intermodal pathways through which auditory information can reach the primary visual cortex. There is clear evidence for intermodal corticocortical pathways linking auditory and visual cortex and also novel connections between the inferior colliculus and the visual thalamus. A recent publication [L.K. Laemle, N.L. Strominger, D.O. Carpenter, Cross-modal innervation of primary visual cortex by auditory fibers in congenitally anophthalmic mice, Neurosci. Lett. 396 (2006) 108–112] suggested the presence of a direct reciprocal connection between the inferior colliculus and the primary visual cortex (V1) in congenitally anophthalmic ZRDCT/An mice. This implies that this mutant mouse would be the only known vertebrate having a direct tectal connection with a primary sensory cortex. The presence of this peculiar pathway was reinvestigated in the ZRDCT/An mouse with highly sensitive neuronal tracers. We found the connections normally described in the ZRDCT/An mouse between: (i) the inferior colliculus and the dorsal lateral geniculate nucleus, (ii) V1 and the superior colliculus, (iii) the lateral posterior nucleus and V1 and between (iv) the inferior colliculus and the medial geniculate nucleus. We also show unambiguously that the auditory subcortical structures do not connect the primary visual cortex in the anophthalmic mouse. In particular, we find no evidence of a direct projection from the auditory mesencephalon to the cortex in this animal model of blindness.     

Primary health care is not cheap: a case study from Guinea Bissau

In 1977 the Ministry of Health in Guinea Bissau started two regional community health projects. In this article we describe the progress of the Tombali project. Three aspects are discussed: the "Learning Process Approach" used in the project; measurement of the effectiveness of the project and the problems of collecting and interpreting these data; and the ratio of investment to recurrent costs and the proportions borne by government and by villagers. Primary health care projects evolve slowly, and the importance of the willingness of project workers, donor agencies, and the national government to work without a blueprint plan is emphasized. We discuss ways of evaluating the success of primary health care schemes; the measurement of any change in health status is difficult and discounts other benefits that may result, such as encouraging community participation and involving villagers in government activities. Both government and villagers contribute significantly to the scheme, the government and donors bearing most of the investment costs, while most of the recurrent costs fall on the villagers. The data show that for neither government nor villagers is the scheme a cheap option to secure health care for rural populations. Finally, we discuss the lessons to be learned by national governments, donor agencies, and health workers from this attempt to implement a primary health care program.