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Background Appendicectomy for acute appendicitis in children may be performed in specialist centres by paediatric surgeons or in general surgery units. Service provision and outcome of appendicectomy in children may differ between such units. Methods This multicentre observational study included all children (aged less than 16 years) who had an appendicectomy at either a paediatric surgery unit or general surgery unit. The primary outcome was normal appendicectomy rate (NAR). Secondary outcomes included 30-day adverse events, use of ultrasound imaging and laparoscopy, and consultant involvement in procedures. Results Appendicectomies performed in 19 paediatric surgery units (242 children) and 54 general surgery units (461 children) were included. Children treated in paediatric surgery units were younger and more likely to have a preoperative ultrasound examination, a laparoscopic procedure, a consultant present at the procedure, and histologically advanced appendicitis than children treated in general surgery units. The unadjusted NAR was significantly lower in paediatric surgery units (odds ratio (OR) 0·37, 95 per cent confidence interval 0·23 to 0·59; P < 0·001), and the difference persisted after adjusting for age, sex and use of preoperative ultrasound imaging (OR 0·34, 0·21 to 0·57; P < 0·001). Female sex and preoperative ultrasonography, but not age, were significantly associated with normal appendicectomy in general surgery units but not in paediatric surgery units in this adjusted model. The unadjusted 30-day adverse event rate was higher in paediatric surgery units than in general surgery units (OR 1·90, 1·18 to 3·06; P = 0·011). When adjusted for case mix and consultant presence at surgery, no statistically significant relationship between centre type and 30-day adverse event rate existed (OR 1·59, 0·93 to 2·73; P = 0·091). Conclusion The NAR in general surgery units was over twice that in paediatric surgery units. Despite a more severe case mix, paediatric surgery units had a similar 30-day adverse event rate to general surgery units. Service provision differs between paediatric and general surgery units.

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We report on the use of the Ilizarov method to treat 40 consecutive fractures of the tibial shaft (35 AO 42C fractures and five AO 42B3 fractures) in adults. There were 28 men and 12 women with a mean age of 43 years (19 to 81). The series included 19 open fractures (six Gustilo grade 3A and 13 grade 3B) and 21 closed injuries. The mean time from injury to application of definitive Ilizarov frame was eight days (0 to 35) with 36 fractures successfully uniting without the need for any bone-stimulating procedure. The four remaining patients with nonunion healed with a second frame. There were no amputations and no deep infections. None required intervention for malunion. The total time to healing was calculated from date of injury to removal of the frame, with a median of 166 days (mean 187, (87 to 370)). Minor complications included snapped wires in two patients and minor pin-site infections treated with oral antibiotics in nine patients (23%). Clinical scores were available for 32 of the 40 patients at a median of 55 months (mean 62, (26 to 99)) post-injury, with 'good' Olerud and Molander ankle scores (median 80, mean 75, (10 to 100)), 'excellent' Lysholm knee scores (median 97, mean 88, (29 to 100)), a median Tegner activity score of 4 (mean 4, (0 to 9)) (comparable to 'moderately heavy labour / cycling and jogging') and Short Form-12 scores that exceeded the mean of the population as a whole (median physical component score 55 (mean 51, (20 to 64)), median mental component score 57 (mean 53, (21 to 62)). In conclusion, the Ilizarov method is a safe and reliable way of treating complex tibial shaft fractures with a high rate of primary union.

This paper reports the occurrence of human parvovirus B19 infection in seven healthcare workers in an acute hospital. The clinical presentation mimicked that of rubella and the diagnosis was made by the detection of human parvovirus B19 IgM antibody in blood samples taken from the affected members of staff. The paper discusses the importance of accurate diagnosis of B19 infection because this virus has been implicated in causing or exacerbating a variety of medical conditions. B19 infection may be serious for people with chronic haemolytic anaemias, those who are immunocompromised or those who are pregnant. B19 infection in pregnancy may be a cause of hydrops fetalis, particularly if the infection occurs during the second trimester. This is in contrast to the risk of intra-uterine rubella infection which is maximal in the first few weeks of pregnancy and which affects fetal development. The paper highlights the need for guidelines for occupational health practitioners on the management of parvovirus B19 infection and the need to make healthcare workers aware of the importance of this infection.

The effect of foscarnet against human immunodeficiency virus (HIV) was evaluated in nine HIV-infected individuals; six completed 28 days of induction therapy. The overall mean increase in CD4+ lymphocytes was 64 cells per mm3. The mean decline in the HIV antigen concentration was 108 pg/ml (P = 0.03), and suppression was related to systemic foscarnet exposure by a maximum-effect pharmacodynamic model.

We have found that Western blots (WBs) of whole platelets exposed to normal autologous or homologous sera commonly have bands at 90 to 95 (95) Kd, and less often at 100 to 110, 80 to 85, 60 to 75, and 50 to 60 Kd when developed with antiglobulins. The percentages of normal sera producing a 95-Kd band with anti-immunoglobulin G (IgG), -IgA, and -IgM are 85, 50, and 30, respectively. Antiglobulin reagents alone also produce background bands on WBs that we have shown correspond to levels of platelet-associated Igs (PAIgs) or their derivatives. Titers of 95 Kd-reactive IgG in normal sera range from 10 to 1,280 (85% less than or equal to 50), and the reaction appears to be partially F(ab')2- mediated. The 95-Kd protein is internal and differs in many respects from surface glycoproteins IIIa, IV, and V of similar apparent molecular weight. In thrombocytopenic patients there was no correlation between severity of thrombocytopenia or PAIgG of platelet eluates and corresponding serum titers of 95 Kd-reactive IgG. Some WB reactions previously reported as evidence of autoimmunity may represent normal variations in reactions of Igs with internal platelet proteins. These reactions may be immunospecific or analogous to nonspecific, partially F(ab')2-dependent binding of Igs by certain bacterial proteins.

Objectives To assess the information preferred by Australian men for a prostate cancer website, to establish such a website, and to assess whether the first 2 years of use of the website reflected those needs. Successful patient information programs must be relevant to the target group’s needs. Methods In phase 1, we surveyed Australian prostate cancer support group members asking for the preferred functions and content of an Australian website. In phase 2, a website was developed ( http://www.prostatehealth.org.au ) with the requested content derived from a urology service, state Cancer Councils, and medical directory and support group organizations. In phase 3, usage patterns of the site were analyzed using Web-Trends software for the first 2 years (2000 to 2002). Results The phase 1 survey of 54 men (response rate 69.2%) showed the most preferred pages were understanding diagnosis/understanding treatment (59%), on-line help-line (49%), and news sections (44%) with listings of Australian support groups (22%). Credible, up-to-date Australian-oriented content was requested. In phase 2, the site developed had five searchable databases with requested medical content from a urology service, support group and treatment center listings, and an on-line help-line run by a cancer council. In phase 3, after 2 years of operation, the site averaged 150,000 hits and 15,000 page views per month, with 46% of visitors from Australian domains. Most visited sections closely followed the needs assessment. Conclusions Needs assessment is an important precursor to targeted web-based education programs. Nonmedical, community-based information is important to men with prostate cancer, as is information on diagnosis and treatment.

SummaryBackground Cutaneous propionibacteria are implicated in acne pathogenesis, although their exact role in the genesis of inflammation is still poorly understood. Agents, including antibiotics, that reduce the numbers of propionibacteria on skin are therapeutic. Resistance in the target organism is a well-recognized consequence of antibiotic therapy for acne but formal prevalence and distribution data are lacking. Objectives To monitor the prevalence of skin colonization by antibiotic-resistant propionibacteria in acne patients attending the dermatology out-patient clinic at Leeds General Infirmary over a 10-year period beginning in 1991, and to examine the distribution of resistant strains on acne-prone skin and in the nares. Methods Propionibacterial samples were obtained from the skin surface of the worst affected site (usually the face) of 4274 acne patients using a moistened swab. The swab was used to inoculate agar plates with and without selective antibiotics. After anaerobic incubation at 37 °C for 7 days, the amount of growth in the presence of each antibiotic was scored on a scale from 0 to 5+. A small number of patients (72) were selected for more detailed quantitative sampling at six different sites to examine the distribution of resistant propionibacteria on acne-prone skin and in the anterior nares. Results The proportion of patients carrying strains resistant to one or more commonly used antiacne antibiotics rose steadily from 34·5% in 1991 to a peak of 64% in 1997. The prevalence dropped to 50·5% during 1999 and then rose again to 55·5% in 2000. Resistance to erythromycin was the most common and the majority of erythromycin-resistant strains were cross-resistant to clindamycin. Resistance to tetracyclines was less common in all years and with little increase over time. The more detailed quantitative study in 72 patients showed that population densities of resistant propionibacteria varied considerably between sites and between individuals. Almost invariably, patients were colonized with resistant strains at multiple sites, including the nares. Conclusions Skin colonization with antibiotic-resistant propionibacteria is much more common now than a decade ago. Resistant propionibacteria are widely distributed on acne-prone skin and in the nares. This suggests that they will be very difficult to eradicate using existing therapeutic regimens, especially from the nasal reservoir.

Postmenopausal Caucasian women aged less than 80 years (n = 99) with one or more atraumatic vertebral fracture and no hip fractures, were treated by cyclical administration of enteric coated sodium fluoride (NaF) or no NaF for 27 months, with precautions to prevent excessive stimulation of bone turnover. In the first study 65 women, unexposed to estrogen (-E study), age 70.8 +/- 0.8 years (mean +/- SEM) were all treated with calcium (Ca) 1.0-1.2 g daily and ergocalciferol (D) 0.25 mg per 25 kg once weekly and were randomly assigned to cyclical NaF (6 months on, 3 months off, initial dose 60 mg/day; group F CaD, n = 34) or no NaF (group CaD, n = 31). In the second study 34 patients, age 65.5 +/- 1.2 years, on hormone replacement therapy (E) at baseline, had this standardized, and were all treated with Ca and D and similarly randomized (FE CaD, n = 17; E CaD, n = 17) (+E study). The patients were stratified according to E status and subsequently assigned randomly to +/- NaF. Seventy-five patients completed the trial. Both groups treated with NaF showed an increase in lumbar spinal density (by DXA) above baseline by 27 months: FE CaD + 16.2% and F CaD +9.3% (both p = 0.0001). In neither group CaD nor E CaD did lumbar spinal density increase. Peripheral bone loss occurred at most sites in the F CaD group at 27 months: tibia/fibula shaft -7.3% (p = 0.005); femoral shaft -7.1% (p = 0.004); distal forearm -4.0% (p=0.004); total hip -4.1% (p = 0.003); and femoral neck -3.5% (p = 0.006). No significant loss occurred in group FE CaD. Differences between the two NaF groups were greatest at the total hip at 27 months but were not significant [p0.05; in view of the multiple bone mineral density (BMD) sites, an alpha of 0.01 was employed to denote significance in BMD changes throughout this paper]. Using Cox's proportional hazards model, in the -E study there were significantly more patients with first fresh vertebral fractures in those treated with NaF than in those not so treated (RR = 24.2, p = 0.008, 95% CI 2.3-255). Patients developing first fresh fractures in the first 9 months were markedly different between groups: -23% of F CaD, 0 of CaD, 29% of FE CaD and 0 of E CaD. The incidence of incomplete (stress) fractures was similar in the two NaF-treated groups. Complete nonvertebral fractures did not occur in the two +E groups; there were no differences between groups F CaD and CaD. Baseline BMD (spine and femoral neck) was related to incident vertebral fractures in the control groups (no NaF), but not in the two NaF groups. Our results and a literature review indicate that fluoride salts, if used, should be at low dosage, with pretreatment and co-treatment with a bone resorption inhibitor.

Percutaneous central venous catheterization can provide reliable temporary hemodialysis access. The current study compared the hemodynamic performance of 28 coaxial catheters to 27 side by side catheters. A total of 675 dialysis sessions were evaluated to assess the flow characteristics of these two designs. The results demonstrated that the side by side catheter provided greater cumulative blood flow with more favorable venous and arterial pressures. Nevertheless, the coaxial catheter performed satisfactorily and met the minimum standards for these devices.

A total of 167 carotid endarterectomies by the eversion technique were completed in 158 patients at a teaching hospital during the 6-year period ending July 1995. The average patient age was 66 years with a range of 39 to 89 years, and 99 (63%) were male. General anesthesia was employed routinely, and temporary indwelling shunts, were not used. Indications for endarterectomy included hemispheric transient ischemic attack (43), amaurosis fugax (20), stroke (41), and asymptomatic stenosis (63). Associated patient risk factors were not significantly different for men and women, and included diabetes mellitus (22%), tobacco abuse (72%), hypertension (69%), hypercholesterolemia (76%), cardiac disease (54%), and renal disease (21%). One (0.6%) permanent operative stroke and two (1%) 30-day hospital deaths occurred. Vascular laboratory follow-up was accomplished by duplex scanning with a documented sensitivity of 98 per cent in detecting aor = 40 per cent stenosis. Eighty-nine per cent (148) of the 167 endarterectomies were tested at least once postoperatively. Overall laboratory follow-up averaged 17 months and ranged from one to 69 months. Residual stenosis, included perioperative thrombosis, occurred in 8 (5%) arteries. Recurrent stenosis was detected in four (2%) cases at 9, 24, 54, and 66 months after endarterectomy. Statistical analyses failed to implicate any specific patient risk factor, age, sex, or operative indication relevant to recurrent stenosis. Residual stenosis was correlated with younger patient age (P = 0.002), female gender (P = 0.12), and endarterectomy on the right side (P = 0.008). Carotid eversion endarterectomy appears to be a universally applicable, safe, and durable operative technique.

The results of colon surgery in all individuals aged 80 years or greater at one teaching institution during the 1987-1993 time period were reviewed. Sixty patients, ranging in age from 80 to 92 years, underwent 41 elective operations and 21 emergency procedures. Emergency procedures resulted in death or a major complication in over one-half of patients, and only six were ultimately able to return home. Conversely, elective procedures were relatively well tolerated, and 31 of 37 survivors returned immediately to independent living (P = 0.006). Mortality was 33.3 per cent in emergency cases versus 9.8 per cent in elective operations (P0.03). The occurrence of a postoperative complication increased the length of stay by an average of 12 days. These data suggest that elective colon surgery in the elderly produces results little different from the population at large. Conversely, emergency operations are associated with a high morbidity and mortality rate. Age alone should not be a determining factor in who undergoes an elective colon operation. Greater efforts should be made to screen elderly individuals to limit emergency surgery.

Concomitant application of 5% w/w benzoyl peroxide and 3% w/w erythromycin has previously been shown to prevent the overgrowth, on the skin of acne patients, of erythromycin-resistant coagulase-negative staphylococci, which occurs when the antibiotic is used alone. Two in vivo studies were carried out to assess the ability of the same therapeutic combination to inhibit the growth of pre-existing erythromycin-resistant propionibacteria and to prevent the selection of resistant strains during treatment. A double-blind clinical trial in 37 patients with mild to moderate acne vulgaris showed that the combination brought about a3 log10 c.f.u. reduction in total propionibacterial numbers/cm2 after 6 weeks therapy (P0.001, Wilcoxon's matched pairs) and also significantly reduced the number of erythromycin-resistant propionibacteria (P0.05). In contrast, erythromycin alone reduced the total propionibacterial count by1.5 log10 c.f.u./cm2 after 6 weeks (P0.05) and did not affect the number of erythromycin-resistant strains. The combined formulation was significantly more effective at reducing total propionibacterial numbers at 6 (P0.01, Mann-Whitney) and 12 weeks (P0.05) than erythromycin alone, although, after 12 weeks, the anti-propionibacterial efficacy of both preparations was less marked. Five patients on combination therapy, and five treated with erythromycin alone, acquired erythromycin-resistant strains de novo at week 6 or week 12. In an open study in 21 acne patients, who each carried10(3) c.f.u. erythromycin-resistant propionibacteria/cm2 skin pretreatment, the combination of erythromycin and benzoyl peroxide reduced the total propionibacterial count by2.5 log10 and the number of erythromycin-resistant strains by a similar amount (P0.001, Wilcoxon). This was accompanied by highly significant reductions in acne grade and lesion counts (P0.001). These data suggest that the combination of 5% w/w benzoyl peroxide and 3% w/w erythromycin has greater in vivo anti-propionibacterial activity than 3% w/w erythromycin alone, and brings about significant clinical improvement in acne patients with high numbers of erythromycin-resistant propionibacterial strains pretreatment.

Glycoproteins (GPs) IIb/IIIa and Ib/IX are principal targets of autoantibodies (autoAbs) in idiopathic thrombocytopenic purpura (ITP). Platelet-associated Abs against GPIIb/IIIa primarily recognize discontinuous or nonlinear epitopes (Fujisawa et al, Blood 81:1284, 1993). This study focused on whether Abs against the extracellular domain of GPIb/IX might react with short linear amino acid (aa) sequences of GPIb alpha. Complementary DNAs (cDNAs) coding for two overlapping fragments of GPIb alpha were amplified, cloned into pFLAG.2 plasmids, and expressed in Escherichia coli DH5 alpha competent cells as FLAG fusion proteins, which were purified by anti-FLAG immunoaffinity chromatography. Of 16 selected ITP sera containing anti-GPIb/IX, 6 reacted in microtiter radioimmunoassays (RIAs) with recombinant protein fragment 2 (aas 240 to 485); 1 also with fragment 1 (aas 1 to 247). When synthetic peptides corresponding to 4 segments of fragment 2 with high antigenic indices (P1 to P4) were used as targets in RIAs, all 6 sera reacted with P2 (aas 326 to 346); 1 also reacted with P4 (aas 389 to 412). P2 was shown to be present on the surface of intact platelets by adsorption studies, and anti-P2 was detected in direct eluates of platelets from ITP patients. Glycocalicin in solution effectively competed with immobilized P2 for anti-P2; P2 in solution was a less effective competitor. Epitope scanning with a panel of synthetic 15-mer peptides localized the P2 epitope to the sequence, TKEQTTFPP. Epitope definition may offer insight into the pathophysiology of and more specific treatments for ITP.

In two cases the menstrual calendar was used to determine the cyclic nature of abdominal pain in women with the Rokitansky syndrome who could not otherwise find a regular pattern in their symptoms. Surgical intervention to remove the rudimentary bicornuate uterus was needed in both, and complete resolution of pain was attained. The menstrual calendar is a valuable diagnostic tool in confirming the cyclic nature of pain and can be used in guiding treatment decisions.

Ventricular sympathetic denervation may occur as a result of myocardial infarction or heart transplantation. The present study examined the time-dependent effects of surgical ventricular sympathectomy on coronary flow and myocardial contractile responses to intracoronary norepinephrine administration in conscious dogs.Adult mongrel dogs (18-26 kg), were either ventricular sympathectomized or served as a sham-operated control. Animals were studied 2, 4, and 8 weeks after surgery. Measurements of left ventricular systolic pressure (LVSP), maximum rate of left ventricular pressure generation (dP/dtmax), maximum negative rate of segmental shortening (-dL/dtmax), heart rate, and mean circumflex flow velocity (CFV) were obtained before and after bolus administration of norepinephrine into the circumflex artery in doses ranging from 0.01 to 0.50 microgram.Intracoronary norepinephrine administration caused significant increases in LVSP, dP/dtmax, -dL/dtmax, heart rate, and CFV. After reaching a peak or maximum response, these variables returned to their respective preinjection values, except for CFV, which exhibited a biphasic response. CFV continued to decline below control levels, indicating a vasoconstrictor response to norepinephrine, before returning back to preinjection levels. With the 0.5-microgram dose of intracoronary norepinephrine, the percent increases in CFV were 124% +/- 25% and 105% +/- 15% (P0.05) at 2 and 4 weeks respectively, compared with the sham-operated controls, which only increased 56% +/- 15%. The response to the 0.5-microgram dose of norepinephrine at 8 weeks (61% +/- 6%) was not significantly different from control. Elevated myocardial contractile responses in the sympathectomized hearts were also evident at 2 and 4 weeks, but not at 8 weeks. The vasoconstrictor response to norepinephrine administration was not significantly different between sympathectomized and sham-operated hearts. Finally, there was no difference in the change in LVSP, dP/dtmax, or heart rate between any of the groups at any of the doses.These results suggest that a supersensitivity to the coronary functional hyperemic response after intracoronary norepinephrine is present in ventricular sympathectomized hearts, but a coronary constrictor supersensitivity does not exist.

Previous work has shown an increase in sympathetic stimulation of the heart during chemical or mechanical irritation of visceral organs, but the involvement of the coronary circulation in such reflexes is not clear. In five preliminary experiments in anesthetized dogs, esophageal distention produced a sympathetic stimulation of the heart, as evidenced by an increase in heart rate, which was abolished by non-selective beta-adrenergic and muscarinic blockades. On the basis of these preliminary data, we further examined a sympathetic coronary constriction during acute esophageal distension in which any direct adrenergic coronary constriction was unmasked by muscarinic blockade with atropine (100 micrograms/kg, i.v.), and non-selective beta-adrenergic blockade with propranolol (1 mg/kg, i.v.). In seven dogs anesthetized with alpha-chloralose in an open-chest procedure, the esophagus was rapidly distended to a pressure of 36 +/- 2 mm Hg, which was not significantly different from the distending pressure used in the preliminary experiments. During esophageal distention, the mean circumflex blood flow decreased to 77 +/- 10% (SEM) of the predistention value. This decrease was statistically significant (p less than 0.05). There was no change in left ventricular pressure, mean arterial pressure dP/dtmax, or heart rate. Intracoronary administration of the nonselective alpha-adrenergic antagonist phentolamine completely abolished the reduction in mean circumflex coronary blood flow caused by esophageal distention in the presence of beta-adrenergic and muscarinic blockades. These results demonstrate a direct sympathetic coronary vasoconstriction elicited by esophageal distention. This vasoconstriction was due to activation of coronary alpha-adrenergic receptors.

The hypothesis that adenosine mediates the coronary vasodilatory response to hypoxia was tested by determining if intracoronary infusion of the adenosine degrading enzyme, adenosine deaminase (ADA), would attenuate this response. Efficacy of ADA was also evaluated by examining its effect on the coronary responses to exogenous adenosine and to 20-s myocardial ischemia. Experiments were conducted in 14 anesthetized, open-chest dogs ventilated 3-5 min with 3% O2-5% CO2-92% N2 to induce systemic hypoxia. Under control, pre-ADA conditions, hypoxia (arterial PO2 19 +/- 2 mmHg) caused left anterior descending (LAD) coronary blood flow to increase from 100 +/- 12 to 382 +/- 47 ml X min-1 X 100 g-1 (+282%). After infusion of ADA (5 U X kg-1 X min-1 for 8-10 min) into the LAD, equally severe hypoxia (arterial PO2 18 +/- 3 mmHg) caused a significantly smaller increase in LAD flow, 79 +/- 9 to 234 +/- 41 ml X min-1 X 100 g-1 (+195%). Oxygen consumption in the LAD perfusion field was unchanged by hypoxia before ADA but fell significantly during hypoxia after ADA. ADA also attenuated significantly the coronary vasodilatory response to exogenous adenosine and to 20-s ischemia. The results of this investigation demonstrate a significant role of adenosine in the coronary vasodilatory response to systemic hypoxia.

Left ventricular responses to 2-min circumflex occlusion were studied in conscious dogs. In nonsympathectomized controls at 2, 4, and 8 wk after surgery for cardiac instrumentation, segmental shortening in the posterior ventricle significantly decreased by 111, 87, and 81% of the preocclusion values, respectively (P less than 0.05). The decrease in shortening was associated with increases in end-diastolic pressure of 9, 9, and 8 mmHg (P less than 0.05), decreases in the maximal rate of pressure generation of 305, 272, and 340 mmHg/s (P less than 0.05), and increases in heart rate of 28, 21, and 20 beats/min, respectively (P less than 0.05). After 2 and 4 wk of ventricular sympathectomy, posterior segmental shortening declined by 38 and 31%, respectively (P less than 0.05), but these decreases were less than in controls (P less than 0.05). Shortening did not change during occlusion after 8 wk of sympathectomy. Diastolic pressure increased by 6 mmHg (P less than 0.05), and the rate of pressure generation decreased by 232 mmHg/s (P less than 0.05) in the 2-wk sympathectomized ventricle. These variables did not change significantly after 4 and 8 wk of sympathectomy. After 2, 4, and 8 wk of sympathectomy, the increases in heart rate during circumflex occlusion were not different from controls (P greater than 0.05). Thus chronic sympathectomy preserved ventricular function during occlusion. This effect was attributable to a reduced preocclusion mechanical performance with a reduction in blood flow requirement and to an increased collateral perfusion, as indicated by a higher peripheral coronary pressure during occlusion in sympathectomized ventricles.

The role of adenosine in pacing-induced hyperemia was examined in 10 dogs. Left coronary blood flow (LCBF), left ventricular O2 extraction [(a-v)O2], and myocardial O2 consumption (MVO2) were monitored. Heart rate (HR) was initially paced at 120 beats/min and then increased to 180 beats/min to elicit a hyperemic response (delta LCBF). During the hyperemia, the vasodilatory response to exogenous adenosine (FAd) was tested. HR was then returned to the initial level, and 20 min after injection of aminophylline (100 mg iv) HR was again increased to 180 beats/min. The response to adenosine was again tested. The pacing-induced increase in MVO2 (delta MVO2) was not affected by aminophylline (P greater than 0.05). However, after aminophylline, the flow response slope delta LCBF/delta MVO2 was decreased by about 20% (P less than 0.05), and the extraction-response slope delta (a-v)O2/delta MVO2 was increased by 100% (P less than 0.05). FAd was also decreased by aminophylline, and the magnitude of the reduction was correlated with the decrease in the flow-response slope (r = 0.82). These results suggest that endogenous adenosine may play an important role in coronary functional hyperemia induced by increases in heart rate.

The participation of endogenous opiates in myocardial performance and coronary blood flow was investigated. Heart rate, left ventricular contractile force (LVCF), left coronary blood flow (LCBF), and left ventricular oxygen extraction were monitored in anesthetized dogs before and after intracoronary opiate receptor blockade with naloxone. LVCF consistently increased in a dose-dependent fashion following intracoronary naloxone. The increasing LVCF was accompanied by significant increases in LCBF and myocardial oxygen consumption, without changes in heart rate. Rapid onset of responses suggested the presence of endogenous opiates operating locally within the myocardium. Similar effects did not follow right atrial injection of naloxone, ruling out a systemic mechanism. Furthermore, naloxone injected into the isolated left anterior descending artery selectively increased contractile force in that perfusion territory while the adjacent untreated circumflex territory showed no change. The administration of dynorphin into the coronaries produced a depression of LVCF qualitatively consistent with these effects. The effect of dynorphin was subsequently reversed with naloxone. These results support the concept that endogenous opiates participate in the regulation of myocardial function through local mechanisms at the myocardial level.

Left coronary perfusion pressure was reduced to 50 mm Hg in alpha-chloralose-anesthetized open chest dogs, causing significant reductions in coronary blood flow and left ventricular oxygen consumption (P less than .05). Infusion of the specific alpha-1 adrenergic antagonist prazosin (0.1 mg/min i.c.) during coronary hypotension significantly increased coronary flow and oxygen consumption within 6 to 8 min. These effects of prazosin were not attenuated by beta adrenergic blockade with propranolol. In the absence of propranolol, infusion of the nonspecific alpha adrenergic antagonist phenoxybenzamine (0.37 mg/min i.c.) increased coronary flow and oxygen consumption within 10 to 15 min, and these increases were significantly greater than with prazosin. In the presence of propranolol, phenoxybenzamine caused increases in coronary flow and oxygen consumption that were not different from those caused by prazosin. The results indicate that 1) prazosin increases coronary flow and oxygen delivery by abolition of a coronary constrictor tone mediated by postsynaptic alpha adrenoceptors; 2) the increases in coronary flow and oxygen consumption caused by phenoxybenzamine in the absence of beta adrenergic blockade were due to antagonism of pre- and postsynaptic alpha adrenoceptors; and 3) the increases in coronary flow and oxygen consumption caused by phenoxybenzamine after beta adrenergic blockade were due entirely to antagonism of coronary postsynaptic alpha-1 adrenoceptors.

A case of laryngeal tuberculosis, in a 21-year-old female, is presented. The pathophysiology and natural course of the disease are discussed. The incidence of apical tuberculosis and associated laryngeal spread is noted.

In alpha-chloralose-anesthetized, open-chest dogs, left coronary blood flow and oxygen extraction were measured at perfusion pressures from 25 to 175 mmHg. Pressure-flow relationships were obtained before and after alpha-blockade with prazosin or alpha 2-blockade with yohimbine in the presence of beta-blockade with propranolol. The efficiency of flow autoregulation with increments in pressure was calculated as the closed-loop gain and as the slope of flow to pressure. In all animals the highest gain and the lowest slope were seen when pressure increased from 75 to 125 mmHg. In the prazosin group before alpha-blockade the gain with this pressure increase was 0.76 +/- 0.05, whereas in the yohimbine group before alpha-blockade this gain was 0.75 +/- 0.03. Prazosin reduced the gain within the pressure range of 75–125 mmHg by 41%, and this reduction was statistically significant (P less than 0.05). Prazosin also significantly increased the flow to pressure slope within this range. In addition, at all pressures greater than or equal to 50 mmHg, the level of coronary flow was significantly increased by prazosin. The increase in flow and the reduction in autoregulatory efficiency with prazosin were not attributable to an increase in myocardial oxygen consumption. Yohimbine had no effects on the level of coronary flow or on the autoregulatory efficiency. These data indicate that an alpha 1-adrenoceptor mediated coronary constriction modulates coronary autoregulation.

Studies were performed to determine whether or not regions of left ventricle become nonperfused in the normovolemic stages of hemorrhagic shock. Using the endothelial fluorescent stain thioflavin S as a tracer, nonperfused myocardium was assessed in six control dogs, eight dogs in early normovolemic shock, and 15 dogs in late normovolemic shock. Nonperfused myocardium was not demonstrable in any of the control animals and in only one of the early shock animals. However, in nine of the late shock animals, nonperfused myocardium was clearly evident, particularly in the anterior and posterior papillary muscles. The demonstration of nonperfused myocardium in late shock is compatible with the concept of a progressively developing edema with a consequent interruption of blood flow.

We have shown that chronic cardiac sympathectomy reduces coronary collateral resistances. The present experiments in isolated dog hearts delineated the role of intramyocardial collateral channels from the septal (SEP) to the circumflex (CIRC), left anterior descending (LAD), and right (RT) coronary arteries in this phenomenon. In 11 controls and 8 2-wk sympathectomized hearts, a retrograde flow technique was used to determine collateral resistances between the epicardial arteries (CIRC, LAD, RT). Collateral resistances between the CIRC and LAD and between the LAD and RT were 42-68% less in sympathectomized hearts (P less than 0.05). Collateral resistances from the SEP to each epicardial artery were determined from retrograde flows simultaneously collected on each epicardial artery when the SEP was the only vessel perfused. Collateral resistances from the SEP to the CIRC and LAD were 51-59% less in the sympathectomized hearts (P less than 0.05). Thus, intramyocardial channels from the SEP to the left coronary arteries show reduced resistances after sympathectomy and can provide a substantial portion of the increased collateral flow to these vessels.

The cardiac response to acute coronary occlusion was studied after chronic ventricular sympathectomy. Infarct size was measured using nitro blue tetrazolium. In 11 control dogs, 8 dogs with ventricles sympathectomized 2 wk earlier, and 5 sham-operated dogs, mean infarct size was 20.0%, 8.9%, and 20.4% of the left ventricular weight, respectively. Infarct size in sympathectomized ventricles was significantly less than in control or sham-operated hearts (P less than 0.05). Left ventricular perfusion before and after coronary occlusion was measured in 10 controls and 7 sympathectomized ventricles using tracer microspheres. Preocclusion flow values in chronically sympathectomized ventricles were approximately 30–40% less than in controls even though arterial pressure and heart rate were no different, suggesting an increased efficiency. Furthermore, after coromanary occlusion, collateral perfusions in the central and peripheral ischemic zones of the sympathectomized ventricles were 200–400% of those in nonsympathectomized ventricles. When collateral perfusion was related to the respective preocclusion flows, the difference between control and sympathectomized ventricles was even greater. Thus, chronic ventricular sympathectomy results in reduced infarct size, and this effect may be due to a reduced flow demand as well as to an increased collateral perfusion.

This study examined the effects of chronic surgical ventricular sympathectomy on the relationships between left ventricular mechanical performance, coronary blood flow, and exercise workload in sham-operated control dogs and dogs which had been ventricular sympathectomized 8 wk earlier. During exercise, left ventricular global contractile state was less in sympathectomized ventricles than in control ventricles, as indicated by reduced systolic pressure and maximal rate of pressure generation. Regional contractile shortening was not different. Heart rate was significantly elevated in sympathectomized ventricles. Therefore, peak systolic pressure-heart rate product and tension-time index were not different in sympathectomized ventricles compared to control ventricles. However, at each level of exercise, mean coronary flow in sympathectomized ventricles was reduced by about 50% compared to control values. The slopes of coronary flow on pressure-rate product and tension-time index were also reduced. No difference in left ventricular oxygen extraction between control and sympathectomized hearts were observed. Thus, chronic ventricular sympathectomy altered the relationships between coronary flow and oxygen consumption, on the one hand, and ventricular oxygen-dependent performance and whole-body exercise level, on the other hand.

Coronary hypoperfusion was elicited in alpha-chloralose-anesthetized open-chest dogs by reducing left coronary perfusion pressure to 50 mmHg. Left coronary blood flow, as well as left ventricular oxygen extraction, oxygen consumption, and contractile force were measured. The reduction in perfusion pressure caused significant reductions in coronary flow, oxygen consumption, and peak reactive hyperemic flow. During hypoperfusion in 11 dogs, intracoronary infusion of the specific alpha 1-adrenergic antagonist prazosin (0.1 mg/min) increased coronary flow and oxygen consumption by 22 and 16%, respectively. Peak increases were observed after 6–8 min of prazosin infusion (0.6–0.8 mg prazosin), and both increases were statistically significant (P less than 0.05). In seven additional dogs, beta-adrenergic blockade with propranolol (1.0 mg ic) did not significantly affect the actions of prazosin. In five additional dogs, the specific alpha 2-adrenergic antagonist yohimbine (1.3 mg ic) in the presence of propranolol (1.0 mg ic) did not affect coronary flow or oxygen consumption during coronary hypoperfusion. Those results suggest that an alpha 1- but not an alpha 2-adrenergic constrictor tone was operative in the left coronary circulation under the conditions of these experiments.

Samples of myocardium from four areas of ischemic and infarcted canine ventricle were examined over a 20-day period for content of the three adenine nucleotides as well as inosine, hypoxanthine, adenosine, and inosine monophosphate. The adenosine triphosphate (ATP) content of central and peripheral areas within the infarct fell to 11% and 8% of control, respectively, 1 day after coronary occlusion. The total adenine nucleotide (TAN) content in these areas fell to 17% of control and showed no significant recovery during the period of study. In the functional myocardium immediately surrounding the infarct the ATP content was depressed to 58% control after 1 day, and the TAN content was also depressed. In the healthy myocardium near the apex, the ATP content was significantly depressed only at the 3-day sample period. Adenine nucleotide derivatives were detected only at 30 min in the central ischemic area. The absence of the nucleoside and nucleobase compounds formed during adenine nucleotide degradation is attributed to their high membrane diffusibility. Loss of these compounds is considered a contributing factor in the prolonged depression of adenine nucleotide content in both ischemic and non-ischemic regions.

Using the tracer microsphere technique, the effect of circumflex artery ligation on regional myocardial perfusion was studied in 8 ventricles which had been sympathectomized 2 weeks earlier and in 9 nonsympathectomized controls. Preocclusion flow values in the chronically sympathectomized ventricles were approximately 75% of those in the controls even though heart rate and arterial pressure were maintained at the same levels in the 2 groups. After circumflex artery ligation, flow to the central ischemic region was slightly greater in the sympathectomized ventricle, but this difference was not statistically significant. However, in the ischemic region adjacent to the central ischemic region, flows in the chronically sympathectomized ventricle were 250--450% of those in the nonsympathectomized ventricle. When these flows were normalized to the preocclusion values, these differences were even greater. Thus, following circumflex artery occlusion, ischemic perfusion of the chronically sympathectomized myocardium is substantially improved.

SummaryThe effects of intravenously infused inosine on myocardial contractile force (MCF) and high-energy phosphate content were studied in 17 open-chest, pentobarbital-anesthetized mongrel dogs following occlusion of small branches of the left anterior descending and circumflex coronary arteries. In 7 dogs, MCF was measured using strain gauge arches sutured in the center of the ischemic area (IMCF), in the periphery of the ischemic area (PIMCF), and in a nonischemic area (NIMCF). After the arteries were ligated and IMCF had stabilized, an infusion of either 50 ml of 50 mM inosine or saline was begun at a rate of 10 ml/min. Inosine infusion produced increases in IMCF, PIMCF, and NIMCF of 32, 41, and 42% of preinfusion levels, respectively. In an additional 10 dogs, adenosine triphosphate (ATP) and creatine phosphate (CP) content of the ischemic myocardium was determined at intervals prior to and following coronary arterial occlusion, during which time either inosine (n = 5) or normal saline (n = 5) was in...

Previous work has suggested that chronic ventricular sympathectomy causes a reduction in coronary collateral resistances. In the present experiments an isolated dog heart procedure was used to directly measure directional collateral resistances in 12 acutely denervated controls and 8 hearts that had undergone ventricular sympathectomy 2 wk earlier. In the procedure, the major coronary arteries were perfused separately but simultaneously during maximum vasodilation, and collateral resistances supplying the vascular beds of the arteries were determined by the double retrograde flow method. In the sympathectomized hearts, all collateral resistances were 47--65% less than in the controls (P less than 0.05). Also, in all hearts, minimum antegrade coronary resistances were determined from pressure-flow relationships in the major coronary arteries. Minimum coronary resistances in the 2 groups were not significantly different (P greater than 0.05). These results indicate that 2 wk of ventricular sympathectomy indeed causes a reduction in coronary collateral resistances, but has no effect on coronary resistances.

The role of adenosine in coronary functional hyperemia was tested using the adenosine antagonist aminophylline. In 11 dogs left coronary blood flow (LCBF) and left ventricular oxygen extraction [(a-v)O2] were monitored. Myocardial oxygen consumption (MVO2) was calculated. Before aminophylline was administered, intracoronary infusion of 6.8 micrograms/min norepinephrine increased LCBF and MVO2 by 40-80%. Simultaneous infusion of adenosine further increased LCBF. Fifteen minutes after injection of 100 mg aminophylline, norepinephrine still increased LCBF, and the ratio delta LCBF/delta MVO2 was unchanged (P greater than 0.05). Although the functional hyperemia was not blunted, the response to infused adenosine was abolished by aminophylline. In 20 additional dogs myocardial adenosine was determined. Before norepinephrine infusion myocardial adenosine with and without aminophylline was 12.7 and 14.3 nmol/g dry wt, respectively (P greater than 0.05). During norepinephrine infusion an increase in adenosine correlated well with increases in MVO2 and LCBF, but the increase in adenosine was not greater after aminophylline. Thus the failure of aminophylline to blunt functional hyperemia was not due to a higher adenosine level after aminophylline. These results do not support a role for adenosine in functional hyperemia elicited by norepinephrine.

Inosiplex was administered to 98 patients with subacute sclerosing panencephalitis (SSPE) in the United States and Canada for variable periods of time up to 9.5 years. Survival data from these 98 patients were compared by life-table analysis with survival in three SSPE control groups drawn from SSPE patients contracting the disease in Israel, Lebanon, or the United States at about the same time as the inosiplex-treated patients but treated differently or not at all. In the inosiplex-treated patients the actuarial probability of survival at 2, 4, 6, and 8 years from onset of SSPE was 78%, 69%, 65%, and 61%, compared with 38%, 20%, 14%, and 8% in a composite control group (p less than 0.01 for all four comparisons). Statistical adjustments for time-to-treatment bias did not affect this result: a modified logrank procedure demonstrated that the risk of dying in the treatment group was 43% of that in the controls. Inosiplex seems to be able to prolong life in patients with SSPE.

Left ventricular contractile force (LVCF), dP/dt, arteriovenous oxygen difference [(a-v)O2], circumflex blood flow (CBF), and myocardial oxygen consumption (MVo2) were determined in dogs during intravenous infusion of inosine at various rates. LCVF and maximal dP/dt increased progressively with increasing infusion rates. CBF increased by 100% at the highest infusion rate, but (a-v)O2 was reduced by 30%. At each infusion rate the increase in MVo2 was only 40% the increase in CBF (P less than 0.05), indicating a nonmetabolically coupled vasodilatation. To further demonstrate this action, the effects of isoproterenol on CBF and (a-v)O2 were compared with those of inosine. During isoproterenol infusion, the increase in CB paralleled the increase in MVo2, and (a-v)O2 showed no change. Intracoronary infusion experiments showed that a 100% increase in flow was caused by an arterial inosine level of about 150 micro M. At inosine levels over 400 micro M, the increase in flow was equal to the maximal increase seen with adenosine infusion.

An occupational health department in a district general hospital in Newcastle upon Tyne screened 487 women of childbearing age for rubella immunity who were prospective employees and whose immunity state was unknown. Ninety per cent of these women were immune. Of the 51 who were found to be susceptible, 29 accepted vaccination.

An analysis of 100 patients sustaining multiple injury and pancreatic trauma was completed. Sixteen patients with penetrating injury died within the first 24 hours, 14 of whom died intraoperatively from major hepatic and/or retroperitoneal venous injury. Eighty-four patients survived long enough to permit evaluation of treatment. There was no statistically significant relationship between mode (p = 0.3) or anatomic area (p = 0.5) of injury and death. However, death was more common in the presence of duct injury (p less than 0.0001). Thirty-nine patients were determined to have duct injury and 45 did not. These two groups were equivalent, with the exception of a higher incidence of concomitant bowel injury (p less than 0.05) in those with duct violation. Combined sump and Penrose drainage was found to be adequate treatment of both proximal and distal nonductal injury with no significant difference in mortality or morbidity rates (p = 0.5). Resection of distal ductal injuries as opposed to drainage alone resulted in significantly lower morbidity and mortality rates (p less than 0.05), comparable to those of drained nonductal injuries. No conclusions could be made relevant to proximal duct injuries, except that drainage alone is inadequate. Seventeen (20 percent) of the 84 patients evaluated died. Pancreatic related mortality rate was 17 percent (14 patients). Two of 23 patients with blunt injury (9 percent) and 12 of 61 patients with penetrating injury (20 percent died). Gram-negative sepsis (82 percent) was the most common cause of death (p less than 0.01), and sepsis was correlated with the presence of pancreatic duct (p less than 0.0001) and bowel (p less than 0.001) injury.

In 17 anesthetized dogs, left coronary blood flow (LCBF), left ventricular oxygen extraction [(a-v)O2], and myocardial oxygen consumption (MVO2) were monitored. Coronary perfusion pressure (CPP) was varied over a wide range by hemorrhage, and the effects of alpha-adrenergic blockade elicited by intracoronary phenoxybenzamine were assessed. During normotension (CPP greater than 80 mm Hg), blockade increased LCBF by 31 +/- 6 (SEM) %, but (a-v)O2 was substantially decreased so that MVO2 was increased by only 13 +/- 3%. At lower levels of CPP, the absolute increase in LCBF caused by blockade was similar to that during normotension, but because of the reduced preblockade LCBF, the percentage increase was greater. Thus, at a CPP of 50-80 mm Hg, LCBF increased by 41 +/- 15%, and at CPP less than 50 mm Hg, LCBF increased by 47 +/- 11% (P less than 0.05 compared to percentage of change during normotension). Furthermore, during hypotension the increase in LCBF after blockade was not accompanied by a large decrease in (a-v)O2. Consequently, in severe hypotension (CCP less than 50 mm Hg), both the absolute increase and the percentage increase in MVO2 was significantly greater than during normotension. These data suggest that during hypotension, especially severe hypotension, an alpha-adrenergic tone in the coronary circulation limits coronary flow and myocardial oxygenation.

After administration of erythro-9-(2-hydroxy-3-nonyl)hypoxanthine, eight compounds were isolated from the urine of rats, dogs, and monkeys. All of the drug metabolites were modified on the nonyl side chain. The oxidatively degraded metabolites included an alcohol (9-(2,8-dihydroxy-3-nonyl)hypoxanthine), the corresponding ketone (erythro-9-(2-hydroxy-8-keto-3-nonyl)hypoxanthine), and three carboxylic acids [erythro-6-hydroxy-5-(9- hypoxanthyl ) hepanoic acid, erythro-7-hydroxy-6-(9- hypoxanthyl )octanoic acid, and erythro-8-hydroxy-7-(9- hypoxanthyl )nonanoic acid]. Glucuronide conjugates of the unchanged drug and the alcohol metabolite were also found. The alcohol, ketone, and nonanoic acid metabolites were produced by all three species. Only the rat produced the shorter chain acid derivatives and no glucuronides. The monkey excreted both glucuronides, while dogs formed one glucuronide conjugate, that of the parent drug.