Search

BACKGROUND\ud The West African outbreak of Ebola virus disease that peaked in 2014 has caused more than 11,000 deaths. The development of an effective Ebola vaccine is a priority for control of a future outbreak.\ud \ud METHODS\ud In this phase 1 study, we administered a single dose of the chimpanzee adenovirus 3 (ChAd3) vaccine encoding the surface glycoprotein of Zaire ebolavirus (ZEBOV) to 60 healthy adult volunteers in Oxford, United Kingdom. The vaccine was administered in three dose levels — 1×1010 viral particles, 2.5×1010 viral particles, and 5×1010 viral particles — with 20 participants in each group. We then assessed the effect of adding a booster dose of a modified vaccinia Ankara (MVA) strain, encoding the same Ebola virus glycoprotein, in 30 of the 60 participants and evaluated a reduced prime–boost interval in another 16 participants. We also compared antibody responses to inactivated whole Ebola virus virions and neutralizing antibody activity with those observed in phase 1 studies of a recombinant vesicular stomatitis virus–based vaccine expressing a ZEBOV glycoprotein (rVSV-ZEBOV) to determine relative potency and assess durability.\ud \ud RESULTS\ud No safety concerns were identified at any of the dose levels studied. Four weeks after immunization with the ChAd3 vaccine, ZEBOV-specific antibody responses were similar to those induced by rVSV-ZEBOV vaccination, with a geometric mean titer of 752 and 921, respectively. ZEBOV neutralization activity was also similar with the two vaccines (geometric mean titer, 14.9 and 22.2, respectively). Boosting with the MVA vector increased virus-specific antibodies by a factor of 12 (geometric mean titer, 9007) and increased glycoprotein-specific CD8+ T cells by a factor of 5. Significant increases in neutralizing antibodies were seen after boosting in all 30 participants (geometric mean titer, 139; P

Urodynamic studies are conducted on a regular basis to evaluate changes in bladder function after spinal cord injury. Often, differences in urodynamic parameters exist from one study or one year to the next. The objective of this study was to provide reference ranges for "normal" variability in urodynamic parameters that can be considered as "no real change" from one study to the next.Retrospective chart review.Fifty consecutive individuals with spinal cord injury had 2 trials (trial 1 and trial 2) of urodynamic studies done 5 minutes apart, and the following data were collected: maximum cystometric capacity, opening pressure, maximum detrusor pressure, volume voided, and postvoid residual. The corresponding data were compared, and the frequency distribution for the change between consecutive studies was plotted. Because there is no standard, variability ranges for 5th to 95th, 10th to 90th, and 25th to 75th percentiles were calculated to give health care providers more choices.Ranges of variability are as follows in the following format (urodynamic parameter; mean value; +, maximum increase; -, maximum decrease)--5th to 95th percentile: cystometric capacity (234.63 mL, +213.50 mL, -158.05 mL); opening pressure (54.56 cmH2O, +30 cmH2O, -18.00 cmH2O); maximum detrusor pressure (60.82 cmH2O, +17.35 cmH2O, -27.80 cmH2O); volume voided (122.20 mL, +177.25 mL, -176.00 mL); postvoid residual (176.06 mL, +197.25 mL, -118.00 mL); 10th to 90th percentile: cystometric capacity (234.63 mL, +126.40 mL, -74.60 mL); opening pressure (54.56 cmH2O, +13.70 cmH2O, -12.00 cmH2O); maximum detrusor pressure (60.82 cmH2O, +10.00 cmH2O, -20.00 cmH2O); volume voided (122.20 mL, +105.60 mL, -82.00 mL); postvoid residual (176.06 mL, +131.00 mL, -86.00 mL); 25th to 75th percentile: cystometric capacity (234.63 mL, +72.00 mL, -27.00 mL); opening pressure (54.56 cmH2O, +4.00 cmH2O, -9.50 cmH2O; maximum detrusor pressure (60.82 cmH2O, +4.00 cmH2O, -10.00 cmH2O); volume voided (122.20 mL, +50.00 mL, -30.00 mL); postvoid residual (176.06 mL, +50.00 mL, -30.00 mL).Urodynamic studies have variability. Knowing these ranges of variability can be helpful in determining whether differences between filling trial 1 and filling trial 2 in a single study or year-to-year changes in urodynamic studies are significant or simply the normal variability of the urodynamic study.

UNLABELLED A new patellofemoral arthroplasty is described, based on a previous design of total knee arthroplasty. The indications are for patients with specific isolated patellofemoral disease with advanced chondral or arthritic damage. The design and technique of insertion is detailed. Three hundred six patellofemoral arthroplasties have been done in 240 patients. The initial results show a high level of pain relief and improvement in function. Two-year followup is available for treatment of 124 knees and 5-year followup is available for treatment of 33 knees. There has been no deterioration in pain or function with followup to 5 years, and there were no late complications attributable to the arthroplasty. Disease progression in the tibiofemoral joint has occurred in 14 patients (16 knees, 5%) requiring revision in 10 of these patients (11 knees, 3.6%). Persistent anterior knee pain was recorded in 14 knees (4%). The short-term results using this new design were better than those of the prosthesis that we used previously, especially concerning malalignment and wear. It offers a reasonable alternative to total knee replacement in the small group of patients with isolated patellofemoral disease. LEVEL OF EVIDENCE Therapeutic study, Level II (prospective cohort study). See the Guidelines for Authors for a complete description of levels of evidence.

This retrospective review of infectious complications was undertaken at two craniofacial centers (Dallas and Philadelphia). Fourteen infections were identified over a 6.5-year period in 567 intracranial procedures primarily for craniosynostosis. There were no infections in infants under 13 months of age and no cases of meningitis. The overall infection rate was 2.5 percent, and 85 percent of infections occurred in secondary reoperative cases. Tracheostomies were not identified as a risk factor for infection. No difference was found in infection rates between patients with shaved and unshaved scalps. Candida and Pseudomonas were the two most common organisms identified, and 28 percent of our infections involved yeast. The average time to diagnose infection was 11.5 days (excluding three patients who averaged 5 months). Thirteen of the fourteen infections were treated surgically with placement of a subgaleal irrigation/drainage system. Initial bony debridement was kept to a minimun. Based on our findings, recommendations are made to further lower infection rates, particularly, those caused by opportunistic organisms.

Two attitudinal scales measuring commitment to abstinence-oriented treatment policies and disapproval of illicit drug use were derived from a survey of 90 staff working in 10 public methadone maintenance clinics in Sydney, Australia. The two scales were shown to be valid constructs by confirmatory factor analysis and to be internally reliable and to have high test-retest reliability. The factors underlying the two scales were highly correlated (r = .77), indicating support for policies that enforce abstinence and limit the duration of maintenance is highly associated with personal disapproval of drug use. There was no significant correlation between staff's knowledge of the benefits of methadone maintenance and their support for abstinence-oriented policies.

Simultaneous recording of adult subjects sipping small amounts of fluid from a cup have been obtained by videofluoroscopy together with feeding respiratory patterns and swallow sounds from the Exeter Dysphagia Assessment Technique (EDAT). These allowed visual representations of respiration and swallow sounds to be superimposed on a videofluoroscopy recording using a split-screen technique. Sequentially numbered, 1/50 sec, half-frame photographic prints were examined and schematic drawings of the relevant radiographs were made. These were superimposed on to the actual EDAT printed chart of the same swallow event, their exact time relationship with respiration and cervical swallow sounds being preserved. The results allow events in the barium videofluoroscopy to be related to events in the feeding respiratory pattern and swallow sounds recorded by EDAT.

Background: The CryoMaze procedure is usually limited to endocardial ablation under cardio-pulmonary bypass. Epicardial ablation is considered inferior as endocardial islets of atrial tissue could theoretically remain viable, protected from cryoinjury by epicardial fat and endocardial circulating warm blood. Novel argon-powered cryoprobes with lower ablation temperatures have recently become available. It is unclear if these instruments can reliably induce transmural atrial fibrosis by epicardial cryoablation on the beating heart. Methods: Ten sheep were divided into two equal groups. CryoMaze ablations were applied using an argon-powered cryoprobe with an ablation temperature of −185°C. In the control group, standardized ablations (n = 50) were applied endocardially under cardiopulmonary bypass. In the experimental group, corresponding ablations (n = 50) were applied epicardially on the beating heart. Postoperatively the animals were monitored for 30 days. At necropsy, the lesions were explanted and analyzed histologically for evidence of transmural fibrosis. Results: Two animals in the control group and one animal in the experimental group died prematurely. Autopsy of the remaining animals showed that all lesions (n = 70) had retained their structural integrity. In the control group, histology demonstrated transmural fibrosis in 94% (28/30) of the endocardially applied lesions. In the experimental group, histology demonstrated transmural fibrosis in 95% (38/40) of the epicardially applied lesions. Statistical analysis revealed no significant difference between the two groups (p = 0.96). Conclusion: Argon-powered epicardial cryoablation on the beating heart is as efficient in inducing transmural fibrosis as the traditional technique of endocardial ablation under cardio-pulmonary bypass. (J Card Surg 2011;26:240-243)

During 7057 conventional cholecystectomies (1972-1991), 16 bile duct injuries occurred, amounting to a risk of 0.22%. A total of 1022 laparoscopic cholecystectomies were performed without such a complication since April 1990. In a retrospective study, 64 patients (16 of our patients and 48 referrals) with an injury or stricture due to conventional cholecystectomy were investigated. In 14 of our 16 patients the injury was recognized and immediately repaired with a good long-term result of 93%, including one successful repair of a subsequent stricture. Two cases of unrecognized injury were managed by nonoperative means. The group of 48 referred patients comprised 10 early postoperative complications (21%) and 38 strictures after an "uneventful" cholecystectomy. Of the 64 total patients, 10 (16%) underwent nonoperative treatment, and 54 required surgery. The mean follow-up period after surgery was 7.4 +/- 4.9 years. Most cases (93%) were repaired by bilioenteric anastomosis (i.e., foremost hepaticojejunostomy) with an 18% restricture rate. Including second and third repairs for restricture, a total of 60 operations (14 primary and 46 secondary reconstructions) were performed without hospital mortality. A good long-term result after stricture repair was achieved in 75% of the patients, whereas 17% had a poor outcome owing to restricture or death (10% had related mortality within 10 years). The other 8% had a moderate result due to recurrent cholangitis. Thus immediate repair of a bile duct injury offers the better chance of a favorable prognosis compared to secondary stricture repair.

A double-blind, parallel-group clinical trial was carried out in 25 patients with post-herpetic neuralgia to determine the efficacy and tolerability of a mixture of gangliosides ('Cronassial') compared with placebo. Patients were allocated at random to receive treatment with either 'Cronassial' (100 mg in 2 ml buffered solution) or placebo given by 11 subcutaneous injections over a period of 27 days, and their symptoms assessed on entry and after 2, 4 and 8 weeks. The four aspects of pain considered (overall pain, hyperaesthesia, stabbing pain and constant ache) all showed maintained reductions in severity with 'Cronassial' treatment, but not with placebo. In the case of hyperaesthesia, this difference between treatments was statistically significant (both during and after the course of injections), even with the relatively small number of patients in this study. Sleep patterns showed significant sustained improvements with 'Cronassial', but not with placebo treatment. Other psychological assessments (general psychological state, appetite and mood) showed little difference between 'Cronassial' and placebo treatment. Although 'Cronassial' was well tolerated systemically, 1 of the 12 patients was withdrawn because of general malaise, and 5 patients had local pain at the injection sites. Two of these 5 patients were withdrawn from the study. There were no withdrawals in the placebo group. It is suggested that further studies employing greater numbers of patients should be carried out to confirm the efficacy of gangliosides in improving symptoms of patients with post-herpetic neuralgia.

The electrocardiogram is often used to gauge the severity of hyperkalemia. We present a case of severe hyperkalemia associated only with pseudonormalized T waves and sinoatrial exit block.

Twenty-one years ago, Howard published a paper entitled "Forty-one Consecutive Whipple Resections Without an Operative Mortality." That paper stimulated the present analysis of the last 118 consecutive pancreatoduodenectomies (107 Whipple and 11 total resections) performed at the Surgical University Clinic Mannheim from November 1985 to the present day with no deaths. Ninety-one resections were performed for neoplasms and 27 were for complicated chronic pancreatitis. The preoperative evaluation, operative technique, and postoperative care of these cases is discussed in detail and compared to the experience of Howard. While there was general agreement on operative technique, there were differences concerning preoperative evaluation (modern imaging methods) and postoperative care (simplification). In this series 21 postoperative complications required seven relaparotomies. Long-term survival after resection for carcinoma was analyzed for 133 consecutive patients who were shown to have true ductal adenocarcinoma. In 76 patients, who had radical (R0-) resections, the actuarial 5-year-survival rate was 36%. In 44 patients, whose R0-resections for pancreatic cancer occurred more than 5 years ago, the actual survival rate was 25%.

1. Furberg CD, Adams HPJ, Applegate WB, Byington RP, Espeland MA, Hartwell T, Hunninghake DB, Lefkowitz DS, Probstfield J, Riley WA: Effect of lovastatin on early carotid atherosclerosis and cardiovascular events. Asymptomatic Carotid Artery Progression Study (ACAPS) Research Group. Circulation 1994;90:1679–1687 2. Hedblad B, Wikstrand J, Janzon L, Wedel H, Berglund G: Low-dose metoprolol CR/XL and fluvastatin slow progression of carotid intima-media thickness: Main results from the Beta-Blocker Cholesterol-Lowering Asymptomatic Plaque Study (BCAPS). Circulation 2001;103:1721–1726 3. Crouse JR III, Byington RP, Bond MG, Espeland MA, Craven TE, Sprinkle JW, McGovern ME, Furberg CD: Pravastatin, Lipids, and Atherosclerosis in the Carotid Arteries (PLAC-II). Am J Cardiol 1995;75:455–459 4. Executive Summary of The Third Report of The National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol In Adults (Adult Treatment Panel III). J Am Med Assoc 2001;285:2486–2497 5. Sacks FM, Moye LA, Davis BR, Cole TG, Rouleau JL, Nash DT, Pfeffer MA, Braunwald E: Relationship between plasma LDL concentrations during treatment with pravastatin and recurrent coronary events in the Cholesterol and Recurrent Events trial. Circulation 1998;97:1446–1452 6. Markwood TT, Kent SM, Coyle LC, Flaherty PJ, O’Malley PG, Taylor AJ: Design and rationale of the ARBITER trial (Arterial Biology for the Investigation of the Treatment Effects of Reducing Cholesterol)—a randomized trial comparing the effects of atorvastatin and pravastatin on carotid artery intima-media thickness. Am Heart J 2001;141:342–347

Fronto-orbital fibrous dysplasia is a progressive disease whose growth does not cease at puberty. It causes frontal protuberance, orbital dystopia, and proptosis. Occasionally, there is a neural entrapment. Malignant change may occur spontaneously or as a result of irradiation. Radical resection offers the greatest chance of cure and correction of the entire deformity. Five patients treated by the Toronto Craniofacial Team are reported. This team has developed techniques for one-stage removal and immediate reconstruction with rib grafts. Rigid fixation of the grafts utilizing the chain-link fence principle has proved that if bone grafts are considered as skin grafts and rapid revascularization is permitted, no resorption or loss of contour occurs.

Tissues from 22 cases of nodular sclerosing Hodgkin's disease were studied by light and electron microscopy in conjunction with immunohistologic and cytochemical staining. The presence of lipid in the cytoplasm of lacunar cells suggested that this was responsible for the distinctive "lacunar" appearance of the cells. Marked morphologic similarities between "blast cells" resulting from mitogen stimulation of lymphocytes in vi-ro, immunoblasts seen in reactive lymphoid tissues, and mononuclear "Hodgkin's" cells in Hodgkin's disease suggested that all three cell types may result from lymphocyte transformation. It also seemed apparent that there was a developmental sequence from lymphocyte to transformed lymphocyte to the abnormal mononuclear Hodgkin's cell, with further progression, through increasing size and nuclear lobulation, to the lacunar cell or, alternatively, to the diagnostic Reed-Sternberg cell. This proposed sequence was supported by immunoperoxidase studies in which cytoplasmic immunoglobulin was demonstrated in mononuclear Hodgkin's cells, lacunar cells and Reed-Sternberg cells. The proposed relationship between these cells was also supported by the findings of both kappa and lambda chains in the same cells, a pattern not seen in reactive transformed lymphocytes.

Uptake studies of the potential endoradiotherapeutic agent, 6- 125 I-iodo-2-methyl-1,4-naphthoquinoI bis(diammonium phosphate) have been carried out in vitro on a wide range of normal and malignant human cells. In general, for a standardized dose of 0.1 μCi/ml, the uptake of the compound into normal cells was 0.0015–0.135 pCi/cell. Uptake into malignant cells was significantly higher than normal cells; uptakes of 0.89–11.3 pCi/cell were noted for melanoma, teratoma of testis, osteosarcoma and adenocarcinoma of colon and pancreas. Comparative uptake ratios formelanoma: Chang liver cells and testicular terastomamormal testis were 29 and 23, respectively. Larger uptake ratios are usually observed with higher doses.

Using an intramyocardial pH needle probe (21 gauge) to monitor myocardial metabolism during ischemia, we determined the effect of potassium cardioplegia at both moderate and deep hypothermia. Five groups of 5 dogs each were placed on cardiopulmonary bypass and the pH probe was inserted approximately 10 mm into the left ventricular free wall. Cardiac ischemia was achieved by cross-clamping the ascending aorta at 37 degrees C (Group 1), 27 degrees C (Group 2), or 17 degrees C (Group 3). In the remaining two groups, aortic cross-clamping was followed by the infusion of 600 to 800 ml of potassium cardioplegic solution adjusted to cardiac temperatures of 27 degrees C (Group 4) or 17 degrees C (Group 5). In each group, myocardial temperature was maintained constant, electrical and mechanical activity observed, and pH recorded until a plateau was reached or for 3 hours. Our results show a progressive and significant decrease in the metabolic rate with reduction in temperature over the 37 degrees to 17 degrees C range. By abolishing contractile activity, potassium cardioplegia markedly reduces the rate of hydrogen ion accumulation at 27 degrees C, but at 17 degrees C the additive effect of cardioplegia is much less pronounced. These observations support the principle of reducing contractile activity to a minimum during elective arrest of the heart but indicate that potassium cardioplegia does little to further reduce the rate of anaerobic metabolism, as shown by the measurement of intramyocardial pH, under conditions of deep hypothermia.

The use of pectoralis major flaps for reconstruction after oral and oropharyngeal resection in a series of seventeen patients is reported. The applications and complications are described. A post-operative assessment of speech, chewing and swallowing in ten of the patients is reported. The functional aspects of such surgery are discussed.

Screening for breast cancer using the combination of physical examination of the breasts and mammography was effective in women age 50 or more in the HIP study. However, major questions remain, especially the benefit of screening women age 40-49, and the independent effect of mammography. Such questions can only be answered by large-scale randomized controlled trials, and trials to answer these questions are now underway in Canada (the NBSS) and Sweden. Only the NBSS, however, is attempting to replicate the HIP study in women age 40-49, and to evaluate the additional contribution of mammography to annual physical examination in women age 50-59. The Swedish studies are evaluating the effectiveness of mammography alone, while studies in Britain will help to evaluate breast self-examination (BSE) and biannual mammography with annual physical examination. Because much of the benefit in HIP could have derived from the physical examination, it is necessary to complete the present trials before population-based screening for breast cancer using mammography can be advocated. Trials are justifiable because the risk of mammographic screening seems likely to be negligible, and the use of the combination of annual mammography and physical examination to be cost-effective. In the meantime, there seems no immediate substitute on a population basis for efficient physical examination of the breasts by primary care physicians coupled with breast self-examination by the woman. Techniques such as ultrasound and diaphanography seem unlikely to supplant mammography in screening, and in any case, have to be evaluated in comparison with mammography.

Two Chinese brothers who underwent sex-change surgery to female status are described. Early life experiences of the two siblings differed from those of their non-transsexual brothers and sisters. The pre-transsexual males were raised primarily by the maternal grandmother, whereas the others were reared by their parents. Feminine role orientation began during childhood and continued through adolescence. Sex-change surgery was performed during adulthood in two stages, and both patients are currently living as women. With the exception of another article in this journal issue, there are no other reports of transsexualism in male siblings.

A study of treatment practices of pediatric centers managing hereditary fructose intolerance and a review of recent literature on this subject were undertaken in an attempt to establish the degree of dietary liberalization allowable with age and the acceptability of foods containing trace amounts of fructose. The information was needed to plan optimal therapy and thus avoid the consequences of the disorder, namely intestinal dysfunction, metabolic imbalance, and hepatic and renal damage. Fifty responses to 113 letters to centers in Canada and the United States, as well as data from The Hospital for Sick Children, Toronto, Ontario, identified only 29 affected children and provided information on their care, including food lists and literature references. Major principles of treatment were similar, but the approach to allowing and quantifying dietary fructose differed. In response to the apparent need for standardization of treatment, the authors formulated improved recommendations for the control of dietary fructose (less than 1.5 gm/day). Only a few foods of vegetable origin are allowed, including a limited selection of vegetables and cereal products from grain endosperm. Repeated dietary counseling is advocated with regard to allowed foods, sweeteners, and medications to ensure long-term dietary compliance.

The results of the treatment of 89 consecutive cases of Pott's paraplegia admitted to care in Korea are reported. Eighty-five patients were treated conservatively. Four patients underwent costo-transversectomy, three of them in the later stages of treatment without apparent benefit. All patients were followed-up for more than one year, 22 (25%) of them for five years or more. 75 patients (84%) recovered sufficiently to walk unaided. 74 patients (83%) returned to normal life and full activity. 64 of these (72%) were neurologically and functionally completely normal and, at the end of follow-up, the other ten (11%) had minimal persistent neurological signs not affecting life and activity. 54 patients (61%) spent less than six months in hospital and 56 (63%) returned to normal activity within one year of the start of treatment. There were two deaths. 41 patients (46%) deteriorated neurologically during the first two months of treatment, but 37 of these recovered completely. The place of chemotherapy as the basis of the treatment of Pott's disease is emphasised. A comparison is made with the published results of other series. The place of operative intervention is discussed and it is argued that the case for urgent early surgical intervention in the treatment of Pott's paraplegia may have been overstated.

This paper analyses the early postoperative complications after 285 pancreaticoduodenectomies performed during the past 15 years in the Surgical University Clinic, Mannheim. There were 235 partial (Whipple) and 52 total pancreatectomies performed for pancreatic and periampullary tumors (181 patients) and complicated chronic pancreatitis (104 patients). A total of 92 complications requiring relaparotomy in 42 patients ended fatally in nine patients. The overall operative and hospital mortality rate was 3.1%. The most frequent and most dangerous were complications at or around the pancreaticojejunal anastomosis, which occurred 25 times with five deaths. Postoperative hemorrhage was seen in 16 patients; endoscopic treatment in four patients and operation in 12 patients was successful in stopping the bleeding in all but one patient. Eight biliary fistulae either ceased spontaneously (3 patients) or after operative reintervention (5 patients) without any mortality. Control of these complications depends on four lines of approach: (1) before operation: optimal preparation of the jaundiced patient including endoscopic transpapillary decompression of the common duct; (2) during operation: a meticulous and standardized technique is mandatory; (3) after operation: continuous observation in the surgical intensive care unit is essential for the timely detection of possible complications; and (4) early reintervention can salvage the great majority of these patients with deleterious complications.

During 1974-1977, 158 infants of birth weights less than 801 gm were referred from outlying hospitals. The survival rate was 25% for the whole group and 35% for those weighing 700 to 800 gm. Many were in a poor condition on arrival. One hundred and nineteen died. The most common causes of death were intracranial hemorrhage (39), RDS (26), and infection (13). Thirty-seven of the 39 survivors were followed until 18 months postterm. Growth failure was common--57% were below the third percentile in weight, 37% in length, and 17% in head circumference. Three had retrolental fibroplasia. Five children (14%) had major neurologic sequelae. Eight were severely handicapped with a Bayley score of less than 70 and ten were moderately handicapped with a Bayley score between 70 and 84, resulting in a neurodevelopmental handicap rate of 49%. Significant factors correlating with survival and intact outcome were birth weight greater than or equal to 700 gm, gestation greater than or equal to 26 weeks, the absence of asphyxia, and good condition on arrival at the NICU. There was no intact survival below 700 gm birth weight. The handicap rate of survivors between 700 and 800 gm was only 39%. Although intensive care in a referral unit may not be justified for those less than 700 gm, every effort should be made in the care of those 700 to 800 gm.

Circular, full-thickness dermal burn- and freeze-produced wounds were produced in rats to compare the difference in healing between the two types of thermal injuries. Contraction did not occur in wounds (n = 30) caused by freezing, while burn wounds (n = 30) contracted to less than one-third of original size by 21 days after injury. If the centers of the freeze-produced wounds (n = 12) were excised, contraction would then occur and proceed at the same rate as an open wound. Histologically, the degree of initial tissue destruction by the two types of injuries was similar. The burn wound contained only half the amount of collagen found in the freeze-produced wound. There was a greater and more rapid replacement of collagen in the burn wounds. With both injuries, the highest concentration of collagen was found on the fifteenth day and returned to normal by the twenty-eighth day. The burn wound contained three times the amount of collagen in normal skin, while the freeze-produced wound contained only 1 3/4 times the amount in normal skin. Contraction does not seem to occur in the healing of the freeze-injured skin because the slow removal and replacement of the residual matrix prevents contraction.

A syndrome of supravalvular pulmonary stenosis and an abnormal facial appearance is described in 15 children. The auscultatory findings suggest stenosis of the pulmonary valve. The presence of an abnormal facial appearance consisting of hypertelorism, a flat nasal bridge, a prominent upper lip, and low-set ears should suggest the correct diagnosis. Angiocardiography shows a constant, thin, “diaphragm-like” radiolucency in the main pulmonary artery. Physical retardation and left-axis deviation on the electrocardiogram are frequently present. Additional cardiac defects were also noted in one third of this group of children. No etiologic factor could be determined.

SUMMARY The developing hard tissues of the teeth of Echinus esculentus are described and figured, and it is noted that calcification occurs in two forms. Attention is drawn to a structural analogy which appears to exist between these two calcified tissues and the primary tissues of vertebrate teeth, despite certain differences in the chemical analysis. This is considered noteworthy in view of the fact that true teeth are generally associated only with the vertebrates.

A modified double lumen perfusion method has been used to study dibasic amino acid absorption in human jejunum. Results using this method have been compared with those from oral load studies. Using the perfusion method, kinetic constants (Kt and Vmax) for lysine were: Kt 4.9 mM; V max 51.3 μmoles min-1 30 cm and for arginine were: Kt 3.8 mM, V max 46.3 μmoles min-1 30 cm Lysine absorption was compared in normal and cystinuric subjects. A significant difference was seen between these groups when studied by perfusion but not using the oral load method. Furthermore, oral load studies using mixtures of lysine, ornithine, and arginine showed a difference between the groups for arginine but no difference for lysine and ornithine. All three dibasic amino acids appeared to be well absorbed in the cystinuric patients. Possible explanations for these differences and the failure of oral tolerance tests to demonstrate the known transport defect in cystinuria are discussed.

In discussing comparative abortion incidence care must be taken in defining abortion and expression and interpreting statistical data. prevalent in urban than rural areas. gal and illegal abortions and between use of abortion and contraception are very complex and not easily analyzed. Japan Hungary and Britain show that a decline in birthrate is due to pre- and post-conceptive control of fertility. computer analysis of a model population using reversible contraception has shown that at least 25% of couples will have one unplanned pregnancy. ion. sterilized after attaining desired family size. es of legal abortion increases with the duration of pregnancy. Morality rates of illegal or clandestine abortion are difficult to establish. le that the death rate for illegal abortion is approaching 1% whereas in developed countries the rate may be 1 in 1000 or less.

Effective pulmonary blood flow was measured in 32 normal infants by an indicator gas technique. To check the accuracy of this technique in the absence of shunts, we obtained 39 pairs of measurements of pulmonary blood flow in anesthetized rabbits by the gas technique and dye dilution. The results showed a high degree of correlation between the two methods of measurement (r = 0.986). Effective pulmonary blood flow was 1.1% less than total pulmonary flow (p < 0.005); this difference was attributed to venoarterial shunting through non- ventilated parts of the lung. Measurements of effective pulmonary blood flow in normal newborn infants increased with age. Before 24 hours of age, mean effective pulmonary flow averaged 138 ml/min/kg or less and gradually rose to a mean value of 166 ml/min/kg (±25.6 SE) at a mean age of 81 hours. It is possible that our measurements of effective pulmonary blood flow before 24 hours of age were falsely low because of the presence of clinically undetectable left-to-right shunts.

Epidermoid inclusion cysts are a relatively common finding following superficial trauma. Inclusion cysts have previously been reported following rhinoplasty, but these have been mucosal cysts and one case of a paraffinoma. A case of multiple recurrent epidermoid inclusion cysts, developing in relation to rhinoplasty, is presented.

cytes forming rosettes with sheep erythrocytes and HTL antigen negative lymphocytes interacting with antigenantibody-complement complexes, Clin EXp lmmunol 14:319, 1973. 2. Yata J, and Tsukimoto I: Maturation of cell surface structure of human B. lymphocytes, Lancet 2:1435, 1972. 3. Darzynkiewicz Z, and Jacobson B: HEPES-buffered media in lymphocyte cultures, Proc Soc Exp Biol Med 136:387, 1971. 4. Lar~dolt RF: Das Knochenmark bei Pertussis, Helv Med Acta 2:153, 1945. 5. Morse SI: Studies on the lymphocytosis induced in mice by bordetella pertussis, J Exp Med 121:49, 1965. 6. Morse SI, and Riester SK: Studies on the leukocytosis and lympbocytosis induced by bordetella pertussis. II. The effect of pertussis vaccine on the thoracic duc~ lymph and lymphocytes on mice, J Exp Med 125:619, 1967. 7. Morse S!, and Riester SK: Studies on the leukocytosis and lymphocytosis induced by bordetella pertussis. I. Radioautographic analysis of the circulating cells in mice undergoing pertussis-induced hyperleukocytosis, J Exp Med 125:401, 1967. 8. Miale J B: Laboratory medicine: Hematology, ed 4, St. Louis, 1972, The C. V. Mosby Company, p 906.

The effect of positive end-expiratory pressure (PEEP) on PaO2 during collapse of a single pulmonary lobe was investigated in seven dogs. Increasing PEEP to the ventilated region of lung increased the proportion of cardiac output flowing to the collapsed lobe and decreased PaO2 and pH. PaCO2 increased at the onset of lobar collapse but was not significantly altered by changes in PEEP. In impaired lungs, the benefits of PEEP may be offset by an increase in blood flow to the unventilated region and hence lead to a decrease in PaO2.

Acupuncture is of no use, or for the optimist of perhaps marginal use, in sensorineural hearing loss, contrary to what is popularly described in China. 5% or less of patients with tinnitus are helped. It is of moderate help in certain types of vertigo, acute labyrinthitis and some aspects of Meniere's disease, whilst it is of great benefit in motion sickness.The treatment is of moderate benefit in ‘nasal catarrh’, sinusitis and recurrent tonsillitis. It is the treatment of first choice in most forms of headache.May I take this opportunity to endorse the critical commentary of Dr. Beagley and his colleagues of the Rawson Report as expressed in your Journal and Hearing and also in the B.M.J, I will add a few of my own comments concerning what are, in my opinion, yet further deficiencies of this otherwise informative and well written report.

This paper reviews the epidemiology of lung cancer in uranium miners in northern Ontario whose cumulative exposure was relatively low and who were exposed only for a short period of time. The development of the "epidemic" is demonstrated chronologically and in terms of latency. An apparent difference between the effects of short-term and of more prolonged radiation is shown. A dose-response effect is demonstrated at all levels. Analysis of tumor type suggests that there may be a difference in dose-response between the two principal types encountered. The relationship of the geographic location of exposure to the final residence at death is reviewed.

Up till now, leukocytes obtained from blood donations have been the main source of human interferon for clinical use. Production from these has been undertaken almost solely by Cantell and his colleagues in Finland, who have devised a highly efficient process (1). However, to make a large amount of this type of interferon entails that buffy coats are handled from many individual donors, which is laborious and expensive, and makes control relatively difficult. If interferon proves to be of value in even some of the clinical trials that are at present underway, then other sources will have to be found if the demand for interferon is to be met.

The term "late metabolic acidosis" is generally used to define a population of apparently healthy LBW infants who fail to grow and have a base deficit in excess of 5 mEq/l (CO2TOT less than 21 mM). A relationship between hypobasemia and the lack of appropriate growth was postulated. This conclusion was reached, however, in the absence of adequate information regarding the distribution of acid-base variables in healthy LBW infants. The results of this study demonstrate that the CO2TOT of LBW infants (n = 114) rises between birth and three weeks of life from a mean of 18.6 to 20.3 mM. The frequency distribution of CO2TOT values did not show any significant deviations from normality, and 2 SD included values as low as 14.5 mM. No difference in the rate of growth was detected between "hypobasemic" infants given a solution of bicarbonate calculated to bring their blood CO2TOT to greater than 21 mM and those given similar amounts of isotonic saline solution. The ability of the LBW infants to excrete an ammonium chloride load was not related to their acid-base status and was comparable to that of term infants. It is apparent that the definition of late metabolic acidosis needs to be reconsidered.

The sera of 20 random human heart transplant recipients, drawn before the administration of immunosuppressive medications, were screened for the presence of factors that might inhibit the mixed lymphocyte reaction. The donors for the lymphocyte cultures were unrelated both to one another and to the heart donor and recipient. Inhibition was defined as a reduction of the number of transformed cells produced in vitro to less than one-third of that produced in autologous serum. It appears that patients who have had previous heart surgery on bypass fare better with heart transplants than those who have not had surgery. This may indicate some change in the overall physiology of the former class of patients resulting in better acceptance of the transplant. In turn, this could be due to the development of a serum factor or an impairment in the patients' cellular immune systems. In the series of recipients studied, the majority possessed serum inhibitory factors possibly non-specific by-products of their heart failure. The precise nature of these factors has yet to be determined. Future research is planned to determine whether bypass surgery is responsible for the stimulation of new immuno-depressive factors or if in some way it boosts the titer of pre-existing factors.

Since 1953, attempts have been made to develop radioactive drugs. Preparations of tritiated menadiol sodium diphosphate (T-MNDP) of high specific activity showed a definite, though limited, but sometimes useful effect in the treatment of certain patients with advanced tumors, especially adenocarcinoms of the colon and of the pancreas and malignant melanoma of the skin. The next step was to use a much more effective isotope. 6- 125 I-iodo-2-methyl-1,naphthoquinol bis (diammonium phosphate) - abbreviated 6- 125 I-iodo-MNDP- has been synthesized, and in laboratory studies appears more promising. 125 I provides radiations which behave predominantly like high LET radiation, despite the accompanying X and gamma radiations. The astatine analogue, 6- 211 At-astato-2rmethyl-1,4-naphthoquinol bis (disodium phosphate) has also been synthesized. Confirming and greatly extending the earlier findings with T-MNDP, n vitro experiments showed that 6- 125 I-iodo-MNDP is concentrated selectively in the cells of some human malignant tumors by a factor of about 15 to 20 or more in relation to the cells of normal origin that were studied. Macrodosimetric considerations and comparison with clinical treatments with T-MNDP' suggest practical dosage. A typical treatment for a patient of body weight 70 kg with localized inoperable carcinoma of the colon could be 8 intravenous injections each of approximately 120mCi of 6- 125 I-iodo-MNDP to a total of 0.97 Ci in 25 days. Risks of late carcinogenesis and leukemogenesis are calculated to be less than 1 %. Clinical indications are discussed briefly. Animal experiments are in progress and further preclinical studies are required.

A double-blind, parallel group, 7-centre trial was carried out to compare the clinical efficacy and patient acceptability of two formulations of sodium cromoglycate for inhalation in patients suffering from asthma. Each single-dose capsule for use in a breath-actuated inhaler contained either a blend of sodium cromoglycate (20 mg) plus lactose (20 mg) or a lactose-free pelletized formulation of sodium cromoglycate (20 mg). Data were summarized from 529 asthmatic patients who had been using the blend formulation for at least 3 months previously. Two hundred and sixty-five patients then received pelletized sodium cromoglycate and 264 patients remained on sodium cromoglycate plus lactose for at least 3 months. Regular assessments were made by patients and clinicians during the trial period of treatment effectiveness. No clinically significant differences were observed between the two formulations after 3 months on test treatment. After a treatment period of 6 months, the pelletized formulation was shown to have some advantages over the blend formulation which were not observed at 3 months, with a significantly higher proportion of 'very effective' assessments being recorded by both patients and clinicians. The capsules of pelletized sodium cromoglycate required significantly less inhalations to empty compared to the capsules of the blend. No differences were observed between the two formulations with regard to the incidence of transient cough and throat irritation after inhalation.

Fibrous dysplasia is an uncommon bone condition with characteristic radiologic features. It is well known that there is increased uptake of Tc-99m hydroxymethylene diphosphonate (HMDP) and methylene diphosphonate (MDP) in fibrous dysplasia. There are no reports of uptake of Ga-67 citrate by fibrous dysplasia. A case is reported in which positive Ga-67 uptake was seen in a patient with polyostotic fibrous dysplasia.