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In mammals, leptin reduces energy intake and may increase energy expenditure as a means to maintain body weight and/or adiposity at an appropriate level. Hibernating mammals seasonally alter body mass, food intake, and body composition and, therefore, represent an attractive model for investigating the physiological regulation of changing body mass and adiposity. Previous experiments in our laboratory demonstrated that administration of mouse recombinant leptin reduces food intake and body weight in arctic ground squirrels during prehibernation fattening. In addition, leptin appeared to reduce metabolic efficiency (weight gain per unit of energy intake). This result suggests that reduced food intake alone may not account for the observed weight loss. Here, we describe the effect of a 3-week constant infusion of leptin given to posthibernation arctic ground squirrels on food consumption and energy expenditure. Mouse recombinant leptin (1 mg/ml) was administered through subcutaneously implanted mini-osmotic pumps (10 microliters/hr flow rate). Resting metabolic rate was monitored before and during the 3-week leptin administration period by indirect calorimetry. Body temperature and locomotory activity were monitored continuously by abdominal radiotransmitters. At the end of the leptin administration period, thermogenic capacity was evaluated by measuring brown fat uncoupling protein-1 mRNA and protein levels. Leptin administration resulted in reduced food intake and prevented posthibernation weight gain, but it did not alter any of the measured parameters of energy expenditure.

Clinicians are increasingly aware that mechanical aspects of foot deformities, such as Charcot changes, clawtoes, bunion deformities, or cavus or planus foot deformities, might have an impact on the occurrence, potential healing, and recurrence of foot ulcers. We report the prevalence of plain radiographic changes and attempt to rate the severity of those deformities in the feet of 456 diabetic veteran medicine clinic enrollees. All 456 radiographs were reviewed by orthopaedic surgeons to specifically identify Charcot changes, presence of arterial calcification, dislocation of the lesser toe metatarsophalangeal joints, hallux interphalangeal joint dislocation, and radiographic evidence of previous surgery. Radiographs of 428 patients were taken while weight-bearing, and these were reviewed to quantify hallux valgus angles, intermetatarsal 1-2 angles, fifth metatarsal-proximal phalangeal angles, second metatarsal lengths, lateral talocalcaneal and talar-first metatarsal angles, and claw toe deformities. The prevalence of Charcot changes was 1.4% (six subjects), and all had radiographic evidence of midfoot Charcot changes. Other deformities, such as clawtoes, hallux valgus, lesser toe joint dislocations, and alterations in arch height, are more common in veterans with diabetes.

A simple method is described for the direct enumeration of viable bacteria dried on test surfaces. Inoculated surfaces were overlayed with agar and after incubation nitroblue tetrazolium solution (pale yellow) was used to stain colonies (purple) at the agar-test surface interface. Stained colonies could be readily detected and counted even against the opaque background of ceramic tile or stainless steel or when present within opaque films of milk or serum. Recovery of bacterial by this method was approximately fivefold greater than using a conventional swabbing procedure. The method was used to demonstrate the marked effect of the composition of the suspension fluid, in which bacteria were dried, and the length of surface exposure upon bacterial survival.

A resuscitative compound in freeze-dried form has been synthesized between a modified starch and a tetremerically stabilized hemoglobin. In order to complex the hemoglobin, the starch has been prepared in mono-, di-, tri-, and tetra-aldehyde moieties. The hemoglobin was stabilized with low molecular weight diacids. Electrophoretic densitometric patterns indicate compound formation. The resulting polymers were characterized with respect to oxygen transport (biotonometry), Hill constant and P50. The in vivo evaluation indicates that these compounds are effective in exchange-transfusion experiments with rats to a level of about 85% replacement of whole blood. The final product is a cost-effective acellular resuscitative compound which can be stored in freeze-dried form at room temperature for extended periods of time. This artificial blood substitute can be reconstituted upon the addition of water.

A survey of 307 Sierra Leonean adolescents between the ages of thirteen and nineteen was assessed to determine their sexual and AIDS-related knowledge, attitudes, and behaviors. Results indicate high sexual activity rates among the sampled group; 89 percent of the males and 68 percent of the females had engaged in sexual intercourse. The mean age at first sexual intercourse was found to be 14.4 years for males and 15.1 years for females. Sixty-five percent of the males and 35 percent of the females reported having three or more sexual partners over their lifetime. Other findings included high rates of STDs and HIV/AIDS, low reported condom use, low reported use of other birth control methods, and low knowledge scores concerning pregnancy prevention, HIV/AIDS and STDs. Implications of these findings are discussed.

Exposure to inescapable shock has been shown to result in reduced consumption of quinine in water (the finickiness effect) in rats. In the present experiment, (a) a clear difference in finickiness occurred between male adult rats exposed to inescapable shock and those exposed to escapable shock (the first such demonstration), (b) finickiness was reinstated 20 days later, and (c) finickiness was eliminated by quinine exposure prior to treatment. The first 2 results support the role of uncontrollability and/or unpredictability in finickiness and extend its potential impact to long-term consequences. This allows greater potential for the modeling of long-term effects, such as eating disorders and depression in humans. The finding that preexposure to quinine eliminated finickiness is contrary to current accounts of the effect. Accounts of finickiness are proposed in terms of classically conditioned aversions, bitterness, and neuropeptide control of ingestion.

We performed a prospective study of the results of treatment of primary cutaneous melanoma of the foot in 282 patients to determine if there were any factors that could predict survival. These patients were part of a group of 1018 patients who had primary cutaneous melanoma affecting the lower extremity. We found that 184 (65 per cent) of the 282 patients had a tumor that extended into the reticular dermis or subcutaneous tissue (a Level-IV or V lesion according to the system of Clark et al.). Sixty-three patients (22 per cent) had evidence of local, regional, or distant metastatic disease at the time of presentation. Location of the melanoma on the plantar aspect of the foot was found to be an independent variable that was associated with a poorer rate of survival (56 per cent at five years and 46 per cent at ten years) compared with a dorsally located melanoma (80 per cent at five years and 67 per cent at ten years). Subungual lesions were associated with an extremely low rate of survival (17 per cent at ten years); however, because of the small number of subungual lesions that were followed, the difference in survival between the patients who had a plantar lesion and those who had a subungual lesion was not significant (p = 0.52). Variables, in order of decreasing importance, that had independent prognostic significance for survival of patients who had a melanoma of the foot were the clinical stage of the lesion at the time of presentation (p < 0.001) and the age of the patient (p < 0.03), as determined by multivariate analysis.(ABSTRACT TRUNCATED AT 250 WORDS)

To evaluate the biophysical properties of two acellular resuscitative fluids, experiments were performed using mixtures of these with suspensions of red blood cells. Two acellular resuscitative fluids were synthesized using a diacid to tetramerically stabilized hemoglobin and then complexing it with either a hydroxyethyl starch or a Tetronic Polyol. The new polymers were characterized with respect to the molecular weight, second virial coefficient and intrinsic viscosity. These fluids were then combined with red cells and the following measurements were made: non-Newtonian flow properties, malonamide induced hemolytic kinetics, sedimentation rates and oxygen transport. The in vitro evaluation indicates that these compounds are effective hemodiluents, offer protection to the red cell membrane and do not cause erythrocyte aggregation. The oxygen transport was satisfactory.

Thirty-seven uncemented primary porous coated anatomic (PCA) total hip arthroplasties (THA) that were performed in 33 patients for the diagnosis of avascular necrosis (AVN) between June 1984 and December 1986 were reexamined at four- to six-year follow-up periods. Final clinical evaluation showed an 86-point average Harris hip rating (range, 47-100 points), which had improved from an average preoperative rating of 42 points (range, 20-61 points). Thigh pain, which was usually not functionally limiting, occurred in 11 patients (25%), and seven patients (16%) had a moderate or severe limp. Nine patients (20%) required the use of a cane. Long-term radiographic evaluation in 37 hips demonstrated acetabular cup migration in one hip, acetabular lucencies in four hips (11%), and acetabular bead loosening in ten hips (27%). Femoral subsidence occurred in five hips (14%) and femoral bead loosening in 11 hips (30%). Thirty hips (81%) demonstrated radiographic evidence of stable bony ingrowth. No revisions were performed for aseptic loosening, but two prostheses were removed for infection. These results of uncemented THA in patients with AVN appear to be as good or better than the results reported for cemented arthroplasty in AVN at this interval of a follow-up period. This study supports the use of uncemented devices, especially with the newer designs and increasing surgical experience in this difficult patient population.

98 patients receiving chemotherapy for cancer were interviewed to determine the prevalence of anticipatory nausea and vomiting, anxiety and dietary changes. Among those who had received at least four treatments 41% reported at least mild anticipatory nausea (AN). For 24% this was a moderate to severe problem, which was significantly associated with a high level of anxiety about treatment. Prevalence at this level was independent of whether the subject was receiving treatment as an in- or an outpatient. Anticipatory vomiting (AV) was reported by only 12 patients, of whom 11 were women; this was the only effect of gender found in the sample. Independence between moderate AN and AV was also suggested by a difference in type of event triggering the effect: predominantly odours for AN and thoughts of the treatment for AV. Changes in diet after commencing chemotherapy were reported by 50% of patients who had received at least four treatments. These most commonly took the form of aversions to meat and then to coffee, and were attributed most frequently to changes in taste and then to loss of appetite.

As healthcare organizations move from isolated departments to integrated information sharing, who will pilot this change? Both the director and manager of pathology data systems at the University of Michigan Hospitals in Ann Arbor suggest vendors, system integrators and hospital administrators put aside competition and try a new concept--"coopetition"--to solve the problem.

Hypothermia during mammalian hibernation is periodically interrupted by arousals to euthermy, the function of which is unknown. We report that arctic ground squirrels (Spermophilus parryii) consistently sleep during these arousals, and that their EEG shows the decrease in slow wave activity (delta power) that is characteristic of a declining requirement for sleep. These results are consistent with the novel hypothesis that the need for sleep slowly accumulates during torpor, and that returning to euthermy is periodically required to allow sleep. Sleep thus seems to be energetically expensive for a hibernating mammal, and cannot be considered solely a strategy for saving energy.

Human immunodeficiency virus type 1 (HIV-1) exhibits extensive genomic and antigenic diversity, which is thought to contribute to the failure of the host's immune response to control infection and prevent clinical progression. Part of this failure may be due to utilization by the virus of antigenic variation as a means to escape protective immune responses. Antibody-escape variants of HIV-1 were studied here using fresh clinical isolates and autologous plasmas. HIV-1 was isolated from the plasma of seven people who were all seropositive for at least 2 years, and symptomatic sometime during that period. Isolated viruses were confirmed as HIV-1 by the presence of reverse transcriptase activity in infected culture supernatants, and by positive immunofluorescence using human monoclonal antibody to HIV-1 core protein. Plasma from these people were positive by Western immunoblot (DuPont) for most major HIV-1 (strain IIIB) antigens. These plasmas neutralized three laboratory strains of HIV-1 (i.e., IIIB, RF, and MN) but did not neutralize the homotypic strain in five cases, and had greatly reduced neutralizing titers against the homotypic strain in two cases. Homotypic neutralizing antibodies were absent in autologous plasma obtained 3 months later. When antibody titers were measured by fixed-cell indirect immunofluorescence assays (IFAs), high titers of IgG (1:6400 to 1:25,600) were detected against HIV-1 IIIB, while low titers of only 1:20 to 1:160 were detected against homotypic viral antigens at the time of virus isolation, and remained low 12 and 16 weeks later. No class IgA, IgD, IgE, or IgM antibodies to homotypic viral antigens, as possible IgG-blocking antibodies, were detected by fixed-cell IFAs. Cross-reactions with heterologous donor's plasmas were observed in some cases, and in these cases the cross-reactions were unidirectional. Live-cell IFAs detected IgG in patient's plasma to HIV-1 IIIB-infected cells but not to cells infected with homotypic isolates. These results suggest that it is common for neutralization-resistant HIV-1 variants to appear during the course of infection, and that all or most antigens of these variants are capable of escaping antibody recognition.

1. The effects of zaprinast (M&B 22948), a selective guanosine 3':5'-cyclic monophosphate (cyclic GMP) phosphodiesterase inhibitor, and sodium nitroprusside on cyclic GMP content, phosphoinositide hydrolysis and airway smooth muscle tone were examined in flurbiprofen pretreated bovine tracheal smooth muscle (BTSM). 2. Anion-exchange chromatography of the soluble fraction of BTSM homogenates resolved three peaks of Ca2+/calmodulin-independent phosphodiesterase (PDE) activity that corresponded to type Ia (cyclic GMP-specific, zaprinast-inhibitable), type II (cyclic GMP-stimulated) and type IV (Ro 20 1724-inhibitable) PDE isoenzymes. Zaprinast caused a selective inhibition of the type Ia PDE isoenzyme (IC50 0.94 microM) with respect to the type II and IV (IC50 s 93 microM and 197 microM respectively) isoenzymes. 3. Pretreatment of BTSM strips with zaprinast (10 microM) for 20 min affected neither the initial rate of force development, nor the resultant magnitude of contraction induced by methacholine (10 microM). In addition, zaprinast (10 microM; 20 min) did not affect the cumulative concentration-response relationship induced by methacholine. In contrast, sodium nitroprusside (300 microM) either alone, or in combination with zaprinast (10 microM), significantly attenuated tone induced by low, but not high concentrations of methacholine. This resulted in a non-parallel, rightwards shift of the methacholine concentration-response curves (nitroprusside: 4.0 fold; nitroprusside/zaprinast: 4.8 fold at the EC50 values), without a reduction in the maximum tone generated. 4. In BTSM slices, zaprinast (10 or 100 microM) did not influence basal or methacholine (10 microM)-stimulated cyclic GMP accumulation or inositol 1,4,5-trisphosphate (Ins(1,4,5)P3) mass accumulation over a 60s incubation period, although it did significantly increase cyclic GMP content over longer (30 min) stimulation periods. 5. In [3H]-inositol prelabelled BTSM slices, stimulated in the presence of 5mM LiCl, methacholine (10 microM) caused a marked increase in total [3H]-inositol phosphate accumulation. This effect was not inhibited by zaprinast (10 microM), sodium nitroprusside (300 microM), or a combination of these drugs despite these agents markedly increasing tissue cyclic GMP content. 6. These findings demonstrate that despite zaprinast being a potent and selective inhibitor of the type Ia PDE isoenzyme in a cell-free system, this drug only increases cyclic GMP content in BTSM following prolonged agonist-stimulation. This may explain its lack of inhibitory effect on methacholine-induced tone. The inability of drugs which increase tissue cyclic GMP content and exhibit anti-spasmogenic activity to inhibit methacholine-stimulated Ins(1,4,5)P3 formation suggests that, unlike vascular smooth muscle, cyclic GMP-dependent mechanisms do not regulate receptor-mediated phosphoinositide hydrolysis in BTSM.

Background: In a sample of 30,195 randomly selected hospital records, we identified 1133 patients (3.7 percent) with disabling injuries caused by medical treatment. We report here an analysis of these adverse events and their relation to error, negligence, and disability., Methods: Two physician-reviewers independently identified the adverse events and evaluated them with respect to negligence, errors in management, and extent of disability. One of the authors classified each event according to type of injury. We tested the significance of differences in rates of negligence and disability among categories with at least 30 adverse events., Results: Drug complications were the most common type of adverse event (19 percent), followed by wound infections (14 percent) and technical complications (13 percent). Nearly half the adverse events (48 percent) were associated with an operation. Adverse events during surgery were less likely to be caused by negligence (17 percent) than nonsurgical ones (37 percent). The proportion of adverse events due to negligence was highest for diagnostic mishaps (75 percent), noninvasive therapeutic mishaps ("errors of omission") (77 percent), and events occurring in the emergency room (70 percent). Errors in management were identified for 58 percent of the adverse events, among which nearly half were attributed to negligence., Conclusions: Although the prevention of many adverse events must await improvements in medical knowledge, the high proportion that are due to management errors suggests that many others are potentially preventable now. Reducing the incidence of these events will require identifying their causes and developing methods to prevent error or reduce its effects.

We tested whether prevention of hibernation in ground squirrels by midwinter exposure to high ambient temperatures influenced timing of the spring phase of reproductive maturation and the phase and period of subsequent circannual rhythms of reproduction and body mass. Exposing hibernating adult male Spermophilus lateralis to 30 degrees C for 6 weeks beginning December 4 advanced the timing of testicular recrudescence by 4-5 weeks, compared to controls left at 4 degrees C. Males exposed to 30 degrees C for 6 weeks beginning at the average time of spontaneous end of hibernation (January 15) reached reproductive maturation at a time intermediate to those of controls and of the December 4 experimental group. However, neither the date of the subsequent fall's body mass peak, the date of the next year's reproductive maturation, nor the periods of circannual rhythms of body mass and reproduction differed among groups. Premature interruption of hibernation appears to allow early expression of reproduction, but does not affect the underlying timing mechanism.

Nine unexpected antibodies of unquestioned clinical significance were detected when the major crossmatch was performed on 31,320 pretransfusion blood samples from 8969 patients whose screening test for unexpected antibodies was nonreactive. Three of the antibodies retrospectively were found to manifest a positive screening test. Another antibody was not detected by the antibody screening test due to an error in preparation of the screening red blood cells. The overriding importance of the major crossmatch is the assurance of ABO compatibility between donor blood and recipient. Therefore, while this study does not resolve whether the antiglobulin phase of the procedure might be considered optional, the major crossmatch should not be eliminated.

Forty-four patients with metastatic breast cancer who had previously received extensive conventional systemic therapy, including combination chemotherapy with doxorubicin, were treated with Bisantrene, a new anthracene derivative. The dose schedule was 250 to 300 mg/sq m body surface administered as a 1- to 2-hr i.v. infusion. Of 40 evaluable patients, there were nine partial responses, and 18 patients had stable disease. Responses were seen in all major sites of organ involvement with a median time to progression of 28 weeks. Moreover, responses were seen among patients who had either failed to respond or had demonstrated refractoriness to prior therapy with doxorubicin, suggesting an apparent lack of cross-resistance between doxorubicin and Bisantrene. Except for myelosuppression and one incidence of acute anaphylactoid reaction, Bisantrene was generally well tolerated by most patients. We believe that Bisantrene may ultimately have a major role in the effective treatment of metastatic breast cancer, and further clinical trials are warranted.

The results of the 1975 CAP Comprehensive Chemistry Survey of serum magnesium are presented. More than 1,260 laboratories participated in this survey. The most commonly used method for the measurement of serum magnesium concentrations is atomic absorption spectrophotometry. Colorimetric dye methods (Rapid-Stat (TM) kits, the Dupont ACA and titan yellow) follow in popularity. Variation in precision was lowest with atomic absorption and highest with titan yellow methods. All three of the dye-binding methods demonstrated either consistently negative or consistently positive biases when compared with the weighted mean concentration. The differences between the mean concentrations obtained by the dye-binding methods and atomic absorption spectrophotometry are statistically analyzed, and several conclusions are presented. As demonstrated by this survey and at the concentrations measured, the estimation of serum magnesium by any of the commonly used methods, except titan yellow, is clinically appropriate.

The incidence of ectopic pregnancies has been expressed in various ways that are not comparable and provide widely differing estimates due to individual definitions of the denominator. Population-based data are presented based on a count of all ectopic pregnancies reported in short stay hospitals in Maine, Rhode Island, and Vermont in 1974-1976. The incidence is 40 per 10(5) female population age 14-44 and is more consistent across 80 hospital service areas than other gynecological diagnoses. The data do not reveal an increasing incidence over these 3 years in contrast to national surveys based on a longer period of observation. A review of determinant factors for ectopic pregnancy is presented, and current theories concerning the etiology, changes in contraceptive practices, innovations in sterilization procedures, or advances in diagnosis do not appear individually or collectively to explain the increasing incidences reported by others. Further basic biologic and epidemiologic research is needed to determine causes and trends in this principal cause of first trimester mortality among pregnant women.

The general principles of cost-benefit analysis are applicable to health care issues, which are in particular need of carefully detailed study at a time when health care expenditures are increasing and when there is competition for scarce resources. There are limitations to such analyses, particularly in the evaluation of the many intangible values so important in the costs and benefits of health care. As examples of the methodology, a simplified cost-benefit analysis is presented for cholecystectomy for silent gallstones in terms of an individual patient, and a more complex analysis is presented for a national program for renal transplantation or chronic hemodialysis for end-stage renal disease. Finally, costs of intensive care support are presented. These examples illustrate advantages and disavantages of a revealing type of analysis that will be applied with increasing frequency to future health care issues.

Between May 1977 and April 1980, 238 patients with operable breast cancer were treated with adjuvant fluorouracil, doxorubicin, and cyclophosphamide (FAC) chemotherapy. All patients were randomized to receive FAC alone or FAC with nonspecific immunotherapy with Bacillus Calmette-Guerin (BCG) vaccine. A randomization for routine postoperative irradiation was included in the study in May 1978. At the median follow-up of 33 months, 53 patients had developed recurrent disease. Up to the present time, there have been no significant differences in the disease-free survival of patients treated with FAC alone from those treated with FAC + BCG (P = 0.21). The disease-free survival for patients treated with and without routine postoperative irradiation was similar (P = 0.99). Disease-free survival of premenopausal and postmenopausal women was similar. The overall estimate of disease-free survival was 72% at 3 years.

This paper discusses the puzzling problem of large differences in per capita use of certain common surgical procedures among neighboring populations, which by all available measures are quite similar in need for and access to services. The evidence reviewed here supports the hypothesis that variations occur to a large extent because of differences among physicians in their evaluation of patients (diagnosis) or in their belief in the value of the procedures for meeting patient needs (therapy). This hypothesis, which we call the professional uncertainty hypothesis, is germane to current controversies concerning the nature and extent of supplier influence on the demand for medical services. It is also important because of its implications for health regulatory policy. Our plan is to (1) review the relevance of the hypotheses for the supplier-induced demand controversy; (2) review the epidemiologic evidence on the nature and causes of variation; (3) examine patterns of use of common surgical procedures to illustrate the importance of supplier influence on utilization; and (4) consider some of the implications of the professional uncertainty hypotheses for public policy.

Seventy-five evaluable patients with metastatic breast cancer refractory to frontline chemotherapy were treated with vinblastine 1.5 mg/m2 by continuous intravenous infusion for five days, intravenous infusion of methotrexate 200 mg/m2, and appropriate calcium leukovorin rescue. Thirty-eight patients were treated with vinblastine followed by methotrexate and calcium leukovorin, while 37 patients were treated with these same drugs in reverse sequence. In 17 patients (23%) an objective remission was achieved, while 39 remained stable for a period in excess of eight weeks. The median duration of remission was two months, and the median duration of survival was six months. The two regimens were well balanced for commonly used pretreatment prognostic factors. There was no difference in response rate and duration of response between the two treatment regimens. In patients with no prior exposure to methotrexate, the remission rate was 37% (11 of 30) compared with 13% (6 of 45). The treatment was well tolerated, and the dose-limiting toxicity was myelosuppression. This combination of drugs is effective in patients who have not been exposed to either drug, while it is only marginally effective in patients previously treated with methotrexate or vinblastine.

Twenty-six patients with clinically documented acute cerebral infarction were evaluated by computed tomography within the first 24 hr. In 21 patients, subtle mass effects and/or focal areas of decreased attenuation corresponding to areas of clinical deficit were demonstrated. Enhancement occurred in only five of 15 infarctions rescanned after contrast administration. In three of these, the region of infarction became isodense after contrast administration. In a patient with multifocal infarcts, enhancement was the only clue to infarction in one focus. The improved spatial and contrast resolution of current generation scanners appears to have significantly increased the sensitivity of computed tomography in demonstrating acute cerebral infarction and has important clinical application.

The annual Papanicolaou smear as a screening test for cervical cancer is evaluated on the basis of cost-effectiveness, predictive value, and other factors of patient selection and comparative trends in mortality rate before and after the introduction of screening programs. For the asymptomatic woman at normal risk for cancer, Papanicolaou smears are recommended only once every five years, although symptomatic or high-risk women should still maintain an annual screening schedule.

The serious question of involuntary hospitalization at this point in history is properly referred to due process in court. While numerous studies have addressed the decisions, statistics and outcomes in this area, insufficient attention has been paid to how the clinician may productively incorporate the clinical experience mobilized by the procedure into the therapeutic work. The authors suggest that the issues raised include maintenance of the alliance, responsibility, dependence, limit-setting, the subjective experience of the process, and the problem of counter-transference. They indicate how the various aspects of commitment may be explored aso as to yield maximal therapeutic benefit, and maintain the alliance during the conflicts of an adversary procedure.

Cost-benefit analysis and cost-effective analysis are formal analytical methods to provide a rational, objective means of comparing total costs with total benefits or of comparing effects in the selection of competing programs for financial support. The use of these techniques in the medical field is a relatively recent development and can aid in future cost containment.

Vascularized first set human skin allografts were rejected largely by a process of extensive and progressive microvascular damage leading to ischemia and infarction. Microvascular injury was associated with a cellular immune response. However, vessel damage was at least in part immunologically nonspecific because vessels of the graft bed (host tissue) were damaged as well as those of the graft itself. We conclude that the microvascular endothelium is the critical target of the immune response in vacularized skin allografts in man, and that this sequence of events--primary vascular damage followed by ischemic infarction--may have significance in a variety of experimental and clinical settings.

Table 1 presents an overview of current gynecologic practice in hospitals as illustrated by three New England states. We believe the balance of diagnoses and operations displayed are reasonably typical of practice elsewhere in the United States. However, since operative rates are lower in New England than in other parts of the country, the proportions of women undergoing hysterectomy or a sterilization procedure will be somewhat higher elsewhere. The general issue of variation in rates of diagnoses and operations is presented; professional uncertainty is a fact which may account for the variation. Further controlled studies are urgently needed to decrease this element of uncertainty and to distinguish too much diagnosis and treatment from too little. Ultimately, nothing less will meet the standards of the best care for patients or satisfy health insurance or government programs that premiums or taxes are supporting an appropriate level of health care.

The authors review 47 patients with closed-head injuries requiring treatment for acute subdural hematoma and report that 21 (45%) survived for 5 days or more. Follow-up study of these 21 survivors led to the following observations: that clinical evaluation of these patients is the most reliable index of their postoperative progress; that the diagnostic usefulness of postoperative cerebral arteriograms is limited because immediate postoperative changes tend to persist; that craniotomy is preferable to burr holes for removal of an acute hematoma; and that the value of cisternography, unless done serially, is limited since posttraumatic hydrocephalus develops rapidly and may persist indefinitely.

Lithium data from the 1975 College of American Pathologists Comprehensive Chemistry Survey program have been analyzed. The results have been organized into five method-dependent groups: four variations on emission flame spectrophotometry, and one group containing all manual atomic absorption methods. The bias observed between flame emission and atomic absorption methods was correlated with the sample mean. In addition, three paired specimens were analyzed by mean comparison. This study indicates that atomic absorption methods have a negative bias, but an apparent correlation with the sample mean indicates the probability of standardization error between the methods. This may be related to a protein depression effect and may be due to differences in viscosity between aqueous standards and serum-based samples. Both atomic absorption and flame emission methods demonstrate variability that is clinically satisfactory.

Medical personnel in a pediatric center were tested for their ability to correctly compute drug doses for sick newborns. One of every 12 doses computed by 95 registered nurses contained an error that would result in the administration of an amount that was ten times higher or lower than the dose ordered. The error rate was no different for experienced or inexperienced nurses. The test also included an evaluation of the nurse's ability to judge the appropriateness of the drug dose ordered for a specified infant. Experienced nurses tended to be more certain, although wrong, in their judgment when compared to inexperienced nurses. Eleven pediatricians, when given the same test, scored higher than the nurses but still made errors at the rate of one of every 26 computations attempted. Five registered pharmacists who were tested demonstrated far better computational skills than either the nursing or physician group.

This study reports the clinical and pathological findings in a patient with recurrent membranous glomerulonephritis following transplantation of an HLA-identical kidney. Such a recurrence has been previously reported only once, although membranous glomerulonephritis is a common cause of nephrotic syndrome in adults. This case confirms that membranous glomerulonephritis may occasionally recur following renal transplantation and demonstrates that immunofluorescence and electron microscopic studies may be necessary to distinguish recurrent, membranous glomerulonephritis from the membranous changes frequently seen with chronic rejection. In light of the apparent low incidence of recurrent membranous glomerulonephritis, renal transplantation remains an excellent therapeutic option in this disease.

Although there appears to be an increased incidence of malignancy among patients with dermatomyositis, demonstration of definitive statistical significance is precluded by the lack of large, controlled series. Patients with the two diseases tend to be older than the general dermatomyositis population and younger than those with cancer alone; and there is a preponderance of female patients. Tumors of the ovary and stomach are more frequently observed than in the general population, while colorectal malignancies are underrepresented. Most reported cases show development of the diseases within a year of one another, and, in some patients, the course of the myopathy follows that of the tumor. No definitive cause for the myopathy in these patients has been established.

Ground squirrels, captured in the field, were housed at ambient temperatures of 23 degrees (photoperiod = 10L:14D) for 13 months. Plasma was sampled at 3 to 4-week intervals and measured for gonadotropin and androgen levels. Testis size was examined monthly by laparotomy. Male ground squirrels showed clear circannual cycles in body mass, testis size, and levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), testosterone (T), and dihydrotestosterone (DHT). During summer and fall, FSH, LH and androgen levels were low, testes were undeveloped, and body mass was increasing. Testes began to rapidly enlarge in January and reached maximum size in February. A rise in FSH preceded gonadal growth but LH remained low until near the time of testis mass peak. LH remained elevated during spring while FSH levels fell and testes regressed. Plasma T and DHT levels generally paralleled LH concentrations; DHT levels were approximately one-fifth those of T levels. During winter animals lost weight but were only occasionally found in a slightly hypothermic condition. Females had elevated plasma LH levels (greater than 1 ng/ml) predominantly in the spring but displayed no cycle in plasma FSH levels. A second group of males held at 4 degrees for 8 months (photoperiod = stimulated natural for 47 degrees N) were regularly torpid during a hibernation season that lasted between November and May. Most (15/21) of these males did not show gonadal development by spring; these non-reproductive males had had restricted body mass gains the previous fall. Plasma FSH was low in both reproductive and non-reproductive males during fall and winter but increased in March while animals were still hibernating. FSH levels continued to increase in April only in reproductive males and reached maximal levels after hibernation was spontaneously terminated. LH titers were elevated in individual males in winter during torpor and were greater in reproductive than in non-reproductive males in May. Androgen levels were undetectable in torpid squirrels, elevated in animals sampled during periodic arousals, and elevated in most males within 3 weeks after terminating hibernation.

An on-line archive of laboratory results designed specifically for ambulatory care areas is described. It is a direct result of paper-flow problems in clinics, which were manifested by numerous phone calls to the laboratory for test results performed up to 10 months ago, and requiring as much as 30 minutes each for retrieval. The archive is incorporated into the result inquiry program of our laboratory computer and is transparent to the user. Utilization of this system by our personnel saves up to 12 hours of work each day. By capturing in a separate file the patient location of each call for outpatient results we are able to identify the clinics that use the telephone for retrieval of test results.

We have investigated the efficacy of intravenous antibiotic therapy as a prophylactic measure to prevent infection following low-velocity gunshot fractures. Ninety-six consecutive patients were randomized prospectively to either an antibiotic group (Group I) or a nonantibiotic group (Group II) and were followed in a special gunshot wound clinic. Only patients with fractures that could be treated by closed techniques and did not require internal fixation were included. Sixty-seven patients (73 fractures) were followed radiographically. At follow-up, 36 fractures in Group 1 and 37 fractures in Group II comprised the study group. A total of two infections, one in each group, was documented. No significant infection prophylaxis was demonstrated by the use of intravenous antibiotics in these injuries.