High-resolution liquid- and solid-state nuclear magnetic resonance of nanoliter sample volumes using microcoil detectors.

The predominant means to detect nuclear magnetic resonance (NMR) is to monitor the voltage induced in a radiofrequency coil by the precessing magnetization. To address the sensitivity of NMR for mass-limited samples it is worthwhile to miniaturize this detector coil. Although making smaller coils seems a trivial step, the challenges in the design of microcoil probeheads are to get the highest possible sensitivity while maintaining high resolution and keeping the versatility to apply all known NMR experiments. This means that the coils have to be optimized for a given sample geometry, circuit losses should be avoided, susceptibility broadening due to probe materials has to be minimized, and finally the B(1)-fields generated by the rf coils should be homogeneous over the sample volume. This contribution compares three designs that have been miniaturized for NMR detection: solenoid coils, flat helical coils, and the novel stripline and microslot designs. So far most emphasis in microcoil research was in liquid-state NMR. This contribution gives an overview of the state of the art of microcoil solid-state NMR by reviewing literature data and showing the latest results in the development of static and micro magic angle spinning (microMAS) solenoid-based probeheads. Besides their mass sensitivity, microcoils can also generate tremendously high rf fields which are very useful in various solid-state NMR experiments. The benefits of the stripline geometry for studying thin films are shown. This geometry also proves to be a superior solution for microfluidic NMR implementations in terms of sensitivity and resolution.

Cell transplantation causes loss of gap junctions and activates GGT expression permanently in host liver.

Cell transplantation into hepatic sinusoids, which is necessary for liver repopulation, could cause hepatic ischemia. To examine the effects of cell transplantation on host hepatocytes, we transplanted Fisher 344 rat hepatocytes into syngeneic dipeptidyl peptidase IV-deficient rats. Within 24 h of cell transplantation, areas of ischemic necrosis, along with transient disruption of gap junctions, appeared in the liver. Moreover, host hepatocytes expressed gamma-glutamyl transpeptidase (GGT) extensively, which was observed even 2 years after cell transplantation. GGT expression was not associated with alpha-fetoprotein activation, which is present in progenitor cells. Increased GGT expression was apparent after transplantation of nonparenchymal cells and latex beads but not after injection of saline, fragmented hepatocytes, hepatocyte growth factor, or turpentine. Some host hepatocytes exhibited apoptosis, as well as DNA synthesis, between 24 and 48 h after cell transplantation. Changes in gap junctions, GGT expression, DNA synthesis, and apoptosis after cell transplantation were prevented by vasodilators. The findings indicated the onset of ischemic liver injury after cell transplantation. These hepatic perturbations must be considered when transplanted cells are utilized as reporters for biological studies.

Human serum albumin microspheres approximate initial organ-specific biodistributions of transplanted hepatocytes and are effective cell surrogates for safety studies.

Liver repopulation with transplanted hepatocytes will generate novel cell-based therapies, although translocation of transplanted cells into lungs through portasystemic shunts has the potential for embolic complications. To facilitate safety analysis of hepatocyte transplantation, we wished to obtain effective cell surrogates and analyzed biodistributions of similarly sized 99mTc-labeled human serum albumin microspheres and rat hepatocytes. Image analysis with dual 99mTc and 111In labels indicated that cells and microspheres were similarly distributed in the liver when injected into normal rats via the spleen. Also, their distributions were similar when injected via a femoral vein or the superior mesenteric vein with cells and microspheres localizing in lungs or liver, respectively. Upon intraportal injection in rats with portal hypertension, microspheres localized in both liver and lungs, consistent with portasystemic shunting. These data demonstrate that human serum albumin microspheres are effective cell surrogates for approximating the safety of hepatocyte transplantation and should be clinically useful.

Quality of life and preferences for treatment following systemic adjuvant therapy for early-stage breast cancer.

PURPOSE: To evaluate the quality of life (QOL) of breast cancer patients who survived 2 to 5 years following initiation of adjuvant cytotoxic and/or hormonal therapy and to characterize relationships between QOL and patient physical symptoms, sexual function, and preferences regarding adjuvant treatment. PATIENTS AND METHODS: Eighty-six patients who had completed systemic adjuvant therapy for early-stage breast cancer between 1988 and 1991 were surveyed by written questionnaire and telephone interview. Sociodemographic information was obtained for each patient, and patients were asked to complete the Functional Living Index-Cancer (FLIC), the Symptom Distress Scale (SDS), the Medical Outcomes Study (MOS) Short Form 36 (SF-36), a series of questions regarding sexual function, and a survey about preferences for adjuvant therapy in relation to possible benefit. RESULTS: The mean FLIC score among all patients was 138.3 (+/- 12.2), which suggests a high level of QOL. The reported frequency of moderate to severe symptoms was generally low (ie, < 15%), with fatigue (31.4%), insomnia (23.3%), and local numbness at the site of surgery (22.1%) occurring with greatest frequency. Patients reported a wide range of sexual difficulties. Preference assessment showed that more than 65% of patients were willing to undergo 6 months of chemotherapy for a 5% increase in likelihood of cancer cure. CONCLUSION: Self-rated QOL in breast cancer patients 2 to 5 years following adjuvant therapy was generally favorable. Less than one third of patients reported moderate to severe symptoms. Selected aspects of sexual function appeared to be compromised. The majority of patients indicated a willingness to accept 6 months of chemotherapy for small to modest potential benefit.

Analysis of hepatocyte distribution and survival in vascular beds with cells marked by 99mTC or endogenous dipeptidyl peptidase IV activity.

Knowledge of the kinetics of cell distribution in vascular beds will help optimize engraftment of transplanted hepatocytes. To noninvasively localize transplanted cells in vivo, we developed conditions for labeling rat hepatocytes with 99mTc-pertechnetate. The incorporated o9mTc was bound to intracellular proteins and did not impair cell viability. When 99mTc hepatocytes were intrasplenically injected into normal rats, cells entered liver sinusoids with time-activity curves demonstrating instantaneous cell translocations. 99mTc activity in removed organs was in liver or spleen, and lungs showed little activity. However, when cells were intrasplenically transplanted into rats with portasystemic collaterals, 99mTc appeared in both liver sinusoids and pulmonary alveolar capillaries. To further localize cells, we transplanted DPPIV+ F344 rat hepatocytes into syngeneic DPPIV-recipients. Histochemical staining for DPPIV activity demonstrated engraftment of intrasplenically transplanted cells in liver parenchyma. In contrast, when 99mTc hepatocytes were injected into a peripheral vein, cells were entrapped in pulmonary capillaries but were subsequently broken down with redistribution of 99mTc activity elsewhere. Intact DPPIV+ hepatocytes were identified in lungs, whereas only cell fragments were present in liver, spleen, or kidneys. These findings indicate that although the pulmonary vascular bed offers advantages of easy accessibility and a relatively large capacity, significant early cell destruction is an important limitation.

Differentiation of pancreatic epithelial progenitor cells into hepatocytes following transplantation into rat liver.

The ability to identify, isolate, and transplant progenitor cells from solid tissues would greatly facilitate the treatment of diseases currently requiring whole organ transplantation. In this study, cell fractions enriched in candidate epithelial progenitor cells from the rat pancreas were isolated and transplanted into the liver of an inbred strain of Fischer rats. Using a dipeptidyl dipeptidase IV genetic marker system to follow the fate of transplanted cells in conjunction with albumin gene expression, we provide conclusive evidence that, after transplantation to the liver, epithelial progenitor cells from the pancreas differentiate into hepatocytes, express liver-specific proteins, and become fully integrated into the liver parenchymal structure. These studies demonstrate the presence of multipotent progenitor cells in the adult pancreas and establish a role for the liver microenvironment in the terminal differentiation of epithelial cells of foregut origin. They further suggest that such progenitor cells might be useful in studies of organ repopulation following acute or chronic liver injury.

Prevalence and predictors of substance use: a comparison between adolescents with and without learning disabilities.

A considerable body of literature has accumulated that examines patterns of substance use and abuse among adolescents attending general education classes. However, much less information exists on the prevalence and predictors of substance use among adolescents with learning disabilities. One purpose of this study was to determine the comparative prevalence of tobacco, alcohol, and marijuana use among a sample of 123 students with learning disabilities (91 male and 32 female, mean age = 14.37 years) and 138 nondisabled students (77 male and 61 female, mean age = 13.71 years). A second purpose was to determine whether two psychosocial variables (self-esteem and type of behavior problem) or severity of drinking problem best predicted use of tobacco and marijuana. Students were administered the Self-Esteem Inventory (SEI)-School form (Coopersmith, 1987) and the Adolescent Drinking Index (ADI) (Harrell & Wirtz, 1989); their teachers completed the Revised Behavior Problem Checklist (RBPC) (Quay & Peterson, 1987). Tobacco and marijuana use were proportionally higher for adolescents with learning disabilities; no differences emerged for alcohol use between groups. A discriminant function analysis revealed that scores on the SEI and subscale scores of the RBPC did not reliably predict tobacco or marijuana use for either group. ADI scores were reliable predictors of marijuana use for students with learning disabilities and tobacco use for both groups.

Teachers' perceptions of factors contributing to children's social status.

Factors related to children's friendships have been empirically related to social development and social status. Identifying specific factors related to peer status is important for teachers and counselors in recognizing children at risk for behavior and emotional problems. 370 teachers' global opinions about the importance of factors associated with peer status were assessed through a statewide survey. Analysis indicated that social skills, physical attractiveness, and outgoingness were the most frequently cited factors contributing to students' social status. Implications for research and practice are discussed.

Family planning services in hospital.

PIP: In India, family planning is accorded top priority in the 5-year plans for health and economic development. The 1st step in getting family planning services integrated with other health services was to integrate them with maternity and child health services at the primary health centers. Services rendered by the hospital were only back-up services. The proposed legislation for abortions, when implemented, will create a greater need for gynecological beds which are already too few. As a result, after abortion the partially motivated person may not be immediately sterilized. When family planning services are functioning in a hospital, staff personnel are likely to better motivated. The family planning services in a hospital should form a unit functioning in a single place. The staffing pattern should include a full-time doctor, a public health nurse, and an extension educator. All hospital personnel should be oriented toward family planning. Cooperation by the obstetrical, gynecological, and pediatric departments is needed in motivating patients. Good motivation of patients is essential for long-run success. Follow-up services are important. To do this, suitable budgetary and transport provision are needed. An adequate system of records should be evolved. To attract patients, the clinic might open earlier than the general outpatient timing. A small exhibit in the central hall with a family planning worker in attendance to give advice and distribute contraceptives would help attract people.^ieng