Zinc as a non-hormonal contraceptive: an alternative to the copper intrauterine device (IUD).

In brief: The many side effects of current contraceptives leave a large proportion of women without adequate protection. This study shows that zinc, a highly physiologically compatible metal, provides effective long-acting reversible contraception in rats, without requiring the use of hormones. Abstract: Long-acting and reversible contraceptives (LARC) are the most widely used form of female contraception worldwide; however, they have significant side effects that often result in early removal. Most LARCs are hormonal, but the use of exogenous hormones is not suitable for all women and causes side effects in many others. The copper IUD (CuIUD) is the only non-hormonal LARC, but a large proportion of users suffer severe side effects. This study proposes the use of zinc as a suitable alternative to the CuIUD. A rat intrauterine device (IUD) model was established to test the efficacy of a zinc IUD (ZnIUD) against a CuIUD. The IUD was surgically implanted into one uterine horn while the other remained untreated. Both the ZnIUD and CuIUD resulted in zero implantation sites which were significantly fewer compared to non-treated horns. Histological assessment revealed damage and inflammation in the endometrium of CuIUD-treated horns but only minor epithelial changes in ZnIUD-treated horns. This suggests ZnIUDs may not share the side effect profile of the CuIUD. To test the long-term efficacy of the ZnIUD, rats had a ZnIUD surgically implanted into both horns and cohoused with males for 3 months. These rats mated regularly but did not get pregnant, confirming long-term effectiveness. Reversibility of the ZnIUD was also established, as removal of the ZnIUD after 3 months resulted in no significant difference in the number of implantation sites between treated and untreated horns. This study demonstrated the contraceptive efficacy of zinc and its potential as a LARC.

Peripheral blood mononuclear cell-derived erythroid progenitors and erythroblasts are decreased in burn patients.

Patients with large burns suffer from anemia of critical illness. Administration of exogenous erythropoietin is ineffective, and transfusion remains the only effective treatment. We have previously shown that erythroid precursors are decreased 1 week after burn in an animal model. Therefore, we have used a two-phase liquid culture system to quantify peripheral blood mononuclear cell (PBMC) compartment-derived erythroid progenitors (EPs) in burn patients. Institutional review board approval and informed consent were obtained. Blood samples were collected at 1 to 30 days after burn, with a mean TBSA of 37.7 ± 15.8% (n = 10; 90% men; age, 46.0 ± 18 years). Four healthy volunteers served as controls. PBMCs were isolated by Ficoll-Hypaque density-gradient centrifugation and were placed in serum-free expansion medium containing cyclosporine A (1 ng/ml), granulocyte macrophage colony-stimulating factor (20 ng/ml), stem cell factor (30 ng/ml), and interleukin-3 (5 ng/ml; phase I). On day 7, cells were reseeded in serum-free expansion medium containing erythropoietin (1 U/ml), holotransferrin (0.3 mg/ml), and stem cell factor (10 ng/ml; phase II). Aliquots from the phase II culture system on day 6 were incubated with anti-CD71, CD235a, and CD36. EPs (CD71 CD36) and erythroblast subpopulations (colony-forming unit erythroids, Proerythroblasts, and intermediate erythroblasts) were identified based on the expressions of CD71 and CD235a by flow cytometry, calculated per million expanded cells, and expressed as a percentage of controls. Total EPs were significantly decreased by days 28 to 31 after the burn (19%; P < .05). Among the erythroblast subpopulations, colony-forming unit erythroids (11%; P < .004) and proerythroblasts (24%; P < .05), were decreased significantly by days 28 to 31 after the burn. PBMCs of burn patients can be used to study impaired erythropoiesis and anemia of critical illness.

Promising antituberculosis activity of the oxazolidinone PNU-100480 relative to that of linezolid in a murine model.

Oxazolidinone antibiotics have activity against Mycobacterium tuberculosis. Linezolid, the only marketed oxazolidinone, has been used off-label in combination regimens to treat multidrug-resistant tuberculosis, but its precise contribution to the efficacy of such combinations is unclear. Another oxazolidinone, PNU-100480, has been demonstrated to have more potent activity in vitro and in a murine model of tuberculosis. In this study, we compared the pharmacokinetics and the antituberculosis activities of these two oxazolidinones over a range of doses and found that linezolid has limited activity at clinically relevant doses in the murine model compared to that of PNU-100480, which has potent bactericidal activity, even at lower drug exposures. These findings were unexpected, given the similar in vitro activities of PNU-100480, its major metabolites, and linezolid. Moreover, the incorporation of PNU-100480 dramatically improved the bactericidal activities of regimens containing current first-line antituberculosis drugs and moxifloxacin. For example, the addition of PNU-100480 (100 mg/kg of body weight/day) to the standard daily regimen of rifampin (rifampicin), isoniazid, and pyrazinamide resulted in an additional 2.0-log(10)-unit reduction in lung CFU counts during the first 2 months of treatment. The combination of PNU-100480, moxifloxacin, and pyrazinamide, which does not contain either rifampin or isoniazid, was also more active than rifampin, isoniazid, and pyrazinamide. These results suggest that PNU-100480 may have the potential to significantly shorten the duration of therapy for drug-susceptible as well as multidrug-resistant tuberculosis.

Implications of differential impacts of care-giving for future research on Alzheimer care.

As the primary caregivers for the millions afflicted with Alzheimer's disease, family members have been the focus of research for the past two decades. Differences in care patterns and deleterious effects of care provision have been clearly established. However, similar demands and hardships associated with care-giving result in different consequences for different families. A greater understanding of the care-giving context and its determinants will enhance knowledge of the differential impacts of care-giving. The most critical determinant of care-giving context is the role relationship between the caregiver and the care recipient. Future research must address role relationship as the primary determinant of what care is provided by whom, and in what manner. This will enhance the understanding of specific caregiver outcomes and lead to optimal targeting of interventions. Future research must also focus on the interface between the family and other social institutions. Evidence calls into question the equity, quality, and capacity of the current system of care, which assumes that family care is best. It will be important for future studies to explore alternate options for long-term care policy. Families and patients will also benefit from studies that assess strategies to ensure an adequate labor pool of qualified formal caregivers.

The influence of gender on incidence and outcome of patients with bladder cancer in Harlem.

Although African Americans have a lower incidence of bladder cancer, overall survival is worse compared with American whites. This phenomenon has been attributed to the higher incidence of advanced disease at diagnosis and poor follow-up. Fifty-nine cases of bladder cancer were identified through the Tumor Registry at Harlem Hospital and reviewed retrospectively. Complete data were obtained for 42 patients. The primary independent variables of interest were primary care utilization, comorbid conditions, social variables, and gender. The outcome variables of interest were stage of disease at presentation and death. The median age at diagnosis in this group was 73 years compared with 68 for bladder cancer patients in the United States. There was no statistically significant correlation between primary care utilization or severity of comorbidities, and clinical stage at presentation. Similarly, these variables did not influence the occurrence of death as an outcome. For women, the mean age at diagnosis was 74.2 years compared with 67.3 in men (P = .112). The ratio of male-to-female cases in this group was 1.3 to 1 compared with 2.7 to 1 for the general US population. Women had lower odds of being diagnosed with superficial disease (OR = 0.24, 95% CI, 0.06-0.94) and a higher incidence of a cancer-specific death (OR = 2.7, 95% CI). The poor outcome and high incidence of bladder cancer cases among women in Harlem is intriguing. Overall, primary care utilization, comorbidities, and other social factors did not seem to influence stage or death as an outcome. The significantly elevated prevalence of smoking among women in this community, increased age at diagnosis, and possible environmental influences may play a role.

Screening for postpartum depression. An antepartum questionnaire.

OBJECTIVE: To develop and evaluate a questionnaire used antepartum to screen for postpartum depression. STUDY DESIGN: Demographic and clinical data, based on previously identified variables, were obtained from 106 second-trimester gravidas (sample I) by interview, self-administered questionnaire and medical record review. The Beck Depression Inventory (BDI) was administered at 1, 6 and 12 weeks postpartum (PP). Statistical analysis, including stepwise linear regression with maximum r-squared improvement, identified a subset of the 24 most predictive variables. This antepartum questionnaire (APQ) was validated retrospectively in the original sample and prospectively in a second group of 99 women (sample II). RESULTS: In both sample populations the APQ had acceptable sensitivity (80-82%) and specificity (78-82%). The incidence of postpartum depressive symptoms (PPDS) rose from 10% to 17% by six weeks without an appreciable decline at 12 weeks (15%). The percentage of women showing more than mild depressive symptoms increased with PP time from 30% at 1 week to 47% at 12. CONCLUSION: The APQ is now available for screening and evaluating early therapeutic intervention in PPDS.

High density sickle cell erythrocyte core membrane skeletons demonstrate slow temperature dependent dissociation.

We have previously demonstrated that slow dissociation of HDSS membrane skeletons in high ionic strength Triton X-100 buffer was related to a posttranslational modification in beta-actin, in which a disulfide bridge was formed between cysteine 284 and cysteine 373[Shartava et al: J Cell Bio 128:805, 1995]. These previous dissociation assays were limited to two homozygous (SS) sickle cell patients and a single temperature (37 degrees C). In the current work, we have expanded the SS subjects to 9 and have carried out dissociation assays at 0, 24, 30, 34, and 37 degrees C. At 0 degrees C there was limited dissociation of spectrin and actin from normal(AA), low density sickle cell(LDSS), and high density sickle cell (HDSS) core skeleton up to 24 hr. The first order rate constants for dissociation of spectrin, at 0 degrees C, was 0.030-0.035 x 10-4 sec-1 for AA,LDSS, and HDSS core skeletons. However at 24, 30, 34, and 37 degrees C the rate of dissociation of spectrin from HDSS core skeletons was significantly slower than the rate of dissociation from AA core skeletons. Having determined the first order rate constants for spectrin dissociation at these specified temperatures, we then asked whether dithiothreitol (DTT) would hasten the dissociation of core skeletons. The presence of DTT caused the rate of dissociation of the HDSS membrane skeleton to become statistically indistinguishable from the rate of dissociation of AA membrane skeletons. This is consistent with the suggestion that reversible thiol oxidation is responsible for the slow dissociation of the HDSS membrane skeleton.

Crafting effective tobacco counteradvertisements: lessons from a failed campaign directed at teenagers.

Focus group research conducted by the Centers for Disease Control and Prevention's Office on Smoking and Health suggested that the desire of teenagers to gain control over their lives would make them responsive to a counteradvertising strategy aimed at exposing the predatory marketing techniques of the tobacco industry. On the basis of this strategy, the office developed draft print advertisements and a rough TV commercial featuring such theme lines as "You get an image. They get an addict." In those ads, "they" referred to cigarette companies. Subsequent testing of the campaign materials, however, indicated that the subtle, sophisticated execution of this concept of manipulation by the industry did not communicate clearly and effectively to an audience of young teens. In fact, 38 percent of those who viewed the rough TV spot believed that the main message promoted smoking. These negative test findings underscore the critical need for ongoing audience research throughout the creative process to ensure that campaign planners stay "in tune" with their consumers.

Unexpected, difficult laryngoscopy: a prospective survey in routine general surgery.

A prospective study of unexpected, difficult laryngoscopy was carried out. During a 7-month period, all general surgery patients in whom the trachea was intubated were assessed; only those with obvious neck pathology were excluded. Ease or difficulty of laryngoscopy was graded by a standard method. There were no grade 4 cases and no failed intubations in a total of 1387 cases. There were significant differences in the results recorded by different individuals; this did not correlate with seniority or with the type of surgery. Four factors have been identified which help to explain these discrepancies. These findings are analysed in relation to the training of junior staff, with particular reference to obstetric anaesthesia.

Postpartum depressive disorders: changing trends.

For centuries, there has been speculation regarding the etiology of postpartum depression. An improved diagnostic classification has emerged, however, as the universality of the syndrome has been recognized and the role of hormonal, genetic, and obstetric variables considered. In addition, different cultures have different perceptions of the needs of the new mother. The emphasis in investigative work now appears to be in the psychosocial and psychodynamic areas. Our recent research focused on identification of risk factors early in pregnancy, including a history of depression, separation from one or both parents in childhood or adolescence, poor parental emotional support in childhood and adulthood, poor relationship with husband or partner, economic problems, and dissatisfaction with amount of education. We suggest that physicians, nurses, and mental health professionals be aware of the emotional status of their patients, familiarize themselves with the risk factors, and initiate a program of careful postpartum follow-up. These measures will help to improve recognition and management of the woman at risk for postpartum depression.

Epidural haematoma requiring surgical decompression following repeated cervical epidural steroid injections for chronic pain.

We report a case of epidural haematoma following a steroid injection into the cervical epidural space. The complication occurred on the seventh such injection over a 2 year period for chronic spinal pain. Surgical decompression over the seventh cervical and the upper 3 thoracic vertebrae was required to alleviate the symptoms of paralysis and anaesthesia. The patient subsequently required skin grafting to the surgical site and two trans-urethral resections of the prostate gland during his 6 week hospital admission. He made a full recovery.

The oesophageal detector device. A prospective trial on 100 patients.

Misplacement of a tracheal tube in the oesophagus remains a significant cause of mortality and morbidity in anaesthesia, despite decades of effort aimed at prevention, or perhaps more importantly, detection, of such an event. We have evaluated a cheap, simple and quick device which relies mainly on the reflation or otherwise of an Ellick's evacuator applied to the supposed 'tracheal' tube. Identical tracheal tubes were passed into the trachea and oesophagus of 100 patients; the left and right position in the mouth was chosen at random. The test was conducted by a second anaesthetist, not present at intubation, and unaware of which tube was in the trachea. There were no false positive results and the correct deduction of which was the tracheal tube was reached in 100 tests using this device. Its use is recommended for widespread evaluation as a valuable adjunct to existing methods of detecting misplacement.

Computerised cardiological case notes.

Optical Mark Reader forms have been used by the Cardiac Department at St Thomas's Hospital for six years to store clinical and haemodynamic data by computer. Forms are completed by clinical staff in outpatients and also for those patients undergoing cardiac catheterisation. Three documents are used to record the symptoms and signs at the clinical consultation, the results of relevant investigations, and the important findings at cardiac catheterisation. These documents are fed into a computer and data from them, together with a limited quantity of types information, are used to produce full clinical reports for our colleagues and the case notes. There reports have saved much secretarial and medical time. A variety of analyses is available for research and management purposes.

Self-administration of D-Ala2-Met-enkephalinamide at hypothalamic self-stimulation sites.

The relationship between the action of enkephalin and the reinforcing action of electrical stimulation in the posterior lateral hypothalamus of the rat was studied with the self-administration approach. Adult male albino rats implanted with a combination cannula and stimulation electrode in hypothalamus were pretested for the reinforcing effects of electrical stimulation. Only subjects that self-stimulated at moderate to high rates were given self-administration tests. The chamber for the self-administration tests was fitted with one lever at each end of a rectangular plexiglass box. In a session, one lever was 'active', the other not. The active lever, if depressed, yielded 20 nl of CSF (artificial cerebrospinal fluid), or CSF in which one of the test substances was dissolved. Each subject was tested repeatedly for the reinforcing effects first of a control solution (CSF), then of D-Ala2-Met-enkephalin (DALA), a long-acting synthetic analogue of enkephalin, then of morphine, and then of opioids mixed with naltrexone or naloxone. Following these tests, the subjects were once again given self-stimulation tests to ascertain the functional integrity of the 'reward' system after the repeated self-administration tests. The results demonstrate that when the test solution was DALA instead of CSF the subjects pressed the active lever at a higher rate than for CSF, and they exhausted the supply more rapidly than for CSF. The rate on the active lever was also significantly higher than on the inactive lever. DALA at 1 and 5 microgram/microliter concentrations proved more reinforcing than at 0.1 microgram/microliter. Naltrexone did not block the reinforcing effect of DALA, whereas naloxone blocked DALA-induced reinforcement. These data extend the report of ventricular methionine-enkephalin positive reinforcement to DALA injected directly into the lateral hypothalamus.

A computer system for clinical microbiology.

The Department of Clinical Microbiology at St Thomas' Hospital has been producing bacteriological reports on a computer for more than three years and is now producing some 2300 reports per week. The system is operated entirely by laboratory staff without special training, and involves the use of optical mark reader (OMR) forms as worksheets, automatic validation and release of most reports, the use of local terminals, and scrutiny of reports by pathologists using a visual display unit. The OMR worksheet records not only the final result but also most of the tests and observations made on the samples; it is the only working document used by technicians. One specialist clinic submits its laboratory requests on an OMR form, which is subsequently used to record the results. The reports are printed and also filed in the computer to produce analyses for hospital, laboratory, and clinical management.

Auditory temporal resolution: effects of sensation level.

Experienced Ss identified (2IFC) the signal complex that contained a gap. When the complexes were of the same frequency, gap detection remained constant over the durations employed (up to 300 msec). When duration of the signal was 10 msec no changes in gap threshold occurred over the range of frequency disparities between signals (up to 120 Hz at F0 = 1 kHz). However, as signal duration increased (beyond 10 msec) there was an increase in gap threshold with increased frequency disparity. The degradation in gap threshold was greater for longer-duration events. Gap threshold was shown to decrease as a function of increase in intensity of the signals.