Scanning electron microscopic changes in the morphology of rabbit pulmonary tissue biopsied following ischemia and reperfusion: a window of opportunity?

Reperfusion is known to cause tissue damage in ischemic pulmonary tissue. We investigated the time frame of this occurrence by examining electron microscopic changes in lung tissue. Isolated, perfused, and ventilated rabbit lungs (and heart) were placed en bloc in a 37 degrees C chamber and perfused through the pulmonary artery at 15 mm Hg pressure with oxygenated Krebs-Henseleit buffer, pH 7.4, 70 ml min(-1), for 20 min and the pulmonary pump and ventilator were stopped. The resultant ischemic state was maintained for 2 h, and reperfusion resumed with the same buffer. The lungs of four groups of rabbits (n = 5 per group) were each subjected to 30 min, 1, 2, and 4 h of reperfusion respectively. Upon completion, lungs were biopsied for scanning electron microscopy. Ischemic damage including the loss of lung architecture, and edema were seen. Reperfusion restored some of the tissue anatomy and the return to normalcy increased up to 1 h of reperfusion after which the damage increased with time. Results suggest that damage due to ischemia alone may be reversible. Initial recovery is due to the re-establishment of circulation. However, with time, the damage seen may be due to free radicals and with 4 h of reperfusion, cell death may have occurred.

Incidence of postinfarction aneurysm within one month of infarct. Experiences with sixteen patients in Hawaii.

BACKGROUND: We report on sixteen patients with a left ventricular aneurysm presenting at less than a month following myocardial infarction. METHODS: All patients had significant left anterior descending coronary artery disease, and in eight cases (50%), this was the only significant pathology. Two patients who were treated conservatively, died within three months of infarction. RESULTS: Of the fourteen surgically treated patients, one died. There have been two late deaths, one at ten months and the other at four years postinfarction. Patients who present early after infarction, usually have a large anterior aneurysm, requiring early surgical repair with ventricular aneurysmectomy and revascularization. This group of patients showed a higher risk for major complications (such as thrombo-embolism, arrhythmias) and/or death. Emergency coronary artery bypass surgery may prove beneficial in the prevention of aneurysm formation by revascularizing the viable but ischemic tissue in that area.

Surgical resection of gastric cancer in the octogenarian population.

The medical records of 80 patients whose mean age was 81.1 years (range 80 to 94 years) were retrospectively evaluated for morbidity, mortality, and survival following gastric resection for gastric carcinoma. The overall 5-year survival of 68 patients who had undergone a total or subtotal gastrectomy for adenocarcinoma was 11%, with a mean and median survival of 25 and 175 months, respectively. In contrast, eight patients who did not undergo gastric resection for adenocarcinoma were found to have a mean and median survival of only 3.6 and 2.0 months, respectively. The 30-day perioperative morbidity and mortality rates for patients who had undergone gastric resection were 45.8% and 5.0%, respectively. The total gastric resection group had no perioperative deaths or anastomotic leaks. We conclude that with careful selection of patients and precise surgical technique, gastric resections can safely be performed in octogenarian patients with minimal morbidity and mortality.

Aggregation and distribution of strains in microparasites.

Recent research has shown that many parasite populations are made up of a number of epidemiologically distinct strains or genotypes. The implications of strain structure or genetic diversity for parasite population dynamics are still uncertain, partly because there is no coherent framework for the interpretation of field data. Here, we present an analysis of four published data sets for vector-borne microparasite infections where strains or genotypes have been distinguished: serotypes of African horse sickness (AHS) in zebra; types of Nannomonas trypanosomes in tsetse flies; parasite-induced erythrocyte surface antigen (PIESA) based isolates of Plasmodium falciparum malaria in humans, and the merozoite surface protein 2 gene (MSP-2) alleles of P. falciparum in humans and in anopheline mosquitoes. For each data set we consider the distribution of strains or types among hosts and any pairwise associations between strains or types. Where host age data are available we also compare age-prevalence relationships and estimates of the force of infection. Multiple infections of hosts are common and for most data sets infections have an aggregated distribution among hosts with a tendency towards positive associations between certain strains or types. These patterns could result from interactions (facilitation) between strains or types, or they could reflect patterns of contact between hosts and vectors. We use a mathematical model to illustrate the impact of host-vector contact patterns, finding that even if contact is random there may still be significant aggregation in parasite distributions. This effect is enhanced if there is non-random contact or other heterogeneities between hosts, vectors or parasites. In practice, different strains or types also have different forces of infection. We anticipate that aggregated distributions and positive associations between microparasite strains or types will be extremely common.

Effects of gastrojejunostomy on pancreatic and gastric carcinoma, pancreatitis, gastric ulcer and other disease states of the gastro-intestinal tract.

BACKGROUND: To evaluate the palliative effects of gastrojejunostomy in patients who have been diagnosed with pancreatic and gastric carcinoma, and other disorders of the gastrointestinal tract. EXPERIMENTAL DESIGN: retrospective medical records review. SETTING: Honolulu area teaching hospital. PATIENTS/PARTICIPANTS: one hundred and thirty-nine patients, 27 of whom had diagnosed pancreatic carcinoma while the remainder had other diagnoses ranging from gastric carcinoma, gastric ulcer, and cancers of nearby anatomical structures such as the ampulla of Vater, between 1985 and 1990. RESULTS: Forty-eight percent (48%) of pancreatic cancer patients were female. The group consisted of 30% Japanese, 30% Caucasian, and 15% Hawaiians/part Hawaiians. Six (22%) underwent a Roux-en-Y gastrojejunostomy (GJ), thirteen (48%) obtained a loop GJ, while the remainder (30%) had a Whipple. Seven (26%) had a biliary bypass besides their GJ. No significant difference existed with regard to the failure of GJ, whether it was performed on a patient with pancreatic cancer or for any other diagnosis. Incidence of delayed gastric emptying was similar between the two groups. CONCLUSIONS: Gastrojejunostomy is effective in patients with pancreatic cancer, and meets the goal of effective gastro-intestinal function regardless of the initial diagnosis.

Localization and surgical treatment of pancreatic insulinomas guided by intraoperative ultrasound.

BACKGROUND: Approximately 20% to 60% of insulinomas cannot be localized preoperatively, and 10% to 20% cannot be found even during surgery. The operative complications associated with the blind surgical explorations are relatively high. METHODS: Between January 1987 and December 1995, intraoperative ultrasound was used to localize insulinomas and guide surgical procedures in 28 patients. RESULTS: Insulinomas were found by intraoperative systematic palpation in 24 patients (85.7%), while intraoperative ultrasound localized the tumors in 27 patients (96.4%). By the combination of these two techniques, all tumors were discovered. The surgical procedures were guided by intraoperative ultrasound. The operative complication rate was 14.3%. CONCLUSION: Intraoperative ultrasound can accurately localize insulinoma, and delineate the spatial relationship between tumor and vital structures, such as pancreatic duct, common bile duct, and critical blood vessels. It can thereby help to increase the successful rate of surgery and avoid unnecessary blind pancreatectomy.

Effects of gastrojejunostomy on pancreatic and gastric carcinoma, pancreatitis, gastric ulcer and other disease states of the gastro-intestinal tract.

BACKGROUND: To evaluate the palliative effects of gastrojejunostomy in patients who have been diagnosed with pancreatic and gastric carcinoma, and other disorders of the gastrointestinal tract. EXPERIMENTAL DESIGN: retrospective medical records review. SETTING: Honolulu area teaching hospital. PATIENTS/PARTICIPANTS: one hundred and thirty-nine patients, 27 of whom had diagnosed pancreatic carcinoma while the remainder had other diagnoses ranging from gastric carcinoma, gastric ulcer, and cancers of nearby anatomical structures such as the ampulla of Vater, between 1985 and 1990. RESULTS: Forty-eight percent (48%) of pancreatic cancer patients were female. The group consisted of 30% Japanese, 30% Caucasian, and 15% Hawaiians/part Hawaiians. Six (22%) underwent a Roux-en-Y gastrojejunostomy (GJ), thirteen (48%) obtained a loop GJ, while the remainder (30%) had a Whipple. Seven (26%) had a biliary bypass besides their GJ. No significant difference existed with regard to the failure of GJ, whether it was performed on a patient with pancreatic cancer or for any other diagnosis. Incidence of delayed gastric emptying was similar between the two groups. CONCLUSIONS: Gastrojejunostomy is effective in patients with pancreatic cancer, and meets the goal of effective gastro-intestinal function regardless of the initial diagnosis.

Internal mammary hypoperfusion syndrome--diagnosis and treatment.

The use of the internal mammary artery (IMA) in coronary artery bypass surgery has increased substantially over the past 20 years, being at present the conduit of choice for most patients. Complications associated with its use occur occasionally and include life-threatening postoperative ischemia or the revascularized myocardium. We reviewed the records of 1,971 consecutive patients who underwent coronary artery bypass grafting over a 5-year period. All operations included an IMA graft to the left anterior descending coronary artery. Twenty-eight of these patients (1.4%) underwent additional placement of a vein graft on the same region as a salvage maneuver for suspected hypoperfusion as a result of IMA failure. All 28 patients showed life-threatening hemodynamic compromise. Twenty-two of the 28 patients (79%) survived. This was the result of immediate surgical correction, which reversed their hemodynamic instability. IMA hypoperfusion was found more frequently in reoperations and in women and diabetic patients. This syndrome is the result of an imbalance between IMA flow and myocardial demand, causing sudden and unexpected myocardial failure. Its detection and expeditious treatment can successfully modify a serious and potentially lethal clinical situation.

Acute epicardial ECG parameters as quantitative predictors of infarct size at 1 week in the baboon.

We describe an experimental baboon model that allows quantitative prediction of myocardial necrosis measured at 1 week from acute epicardial ECG parameters recorded from a high-resolution matrix of fixed epicardial electrodes. The electrode grid overlies a circumscribed area of ultimate necrosis, produced by the occlusion of a selected diagonal branch of the left anterior descending coronary artery (LAD). This grid allowed examination of the pattern of changes in ST segment elevation (ST increases) throughout their return to control levels, and profiled changes in the distribution of electrodes recording TQ-ST segment deflections. Those points more centrally located within the area of ST increases consistently showed greater absolute values of ST increases and remained elevated longer than the more peripheral electrodes. Areas of the electrode matrix corresponding to those electrode points showing significant ST increases (2 mV above control) at each recording interval through 8 hr were fitted to the area of necrosis underlying this electrode grid. While the maximum area of ST increases (maxAst) uniformly overestimated infarct size between animals on the order of 25%, regression analysis allowed prediction of the extent of infarct from maxAst with an error of only 5%. Correlation of maxAst with the epicardial extent of infarct, total weight, and volume yielded coefficients of 0.95, 0.85, and 0.91 respectively, while mean ST increases (ST increases) showed a poorer correlation with respective coefficients of 0.49, 0.55, and 0.39. MaxAst proved to be the single best predictor of infarct size assessed at 1 week.

Effect of anticoagulants on the incidence of late pericardial tamponade following open heart surgery. The Hawaii experience.

We report on 17 cases of late pericardial tamponade (LPT, > 60 hours postoperatively) occurring post aortic and/or mitral valve replacement or coronary artery bypass graft surgery between 1979 and 1994. This includes one patient in whom LPT occurred twice. These cases were found from a search of 374 patients including those who were diagnosed with hemorrhagic complications secondary to open heart surgery, pericardial effusion and tamponade, those who underwent pericardiocentesis and a randomly picked group of patients. The mean age of the group was 57.8 years and included 11 males and 6 females. Due to the relatively small size of our sample (reflecting the infrequency of this complication) we force matched this tamponade group to look for any relationships that may exist between the incidence of LPT and anticoagulant therapy. No significant difference was found between the two groups with documented preoperative anticoagulant therapy (number of days; p > 0.2) or in relation to coagulation tests (prothrombin time, partial thromboplastin time and platelet counts; p > 0.2). In our case series, anticoagulant therapy did not appear to significantly affect the incidence of LPT.

Open heart surgery in patients with end-stage renal disease.

This case-control study evaluated the mortality and morbidity in patients with end-stage renal disease (ESRD) who underwent open heart surgery, as compared with matched control patients. Outcome measures included length of use of ventilators, vasopressor agents, number of blood units transfused, chest tube output, and length of stay. Hospital length of stay was longer in patients with renal failure, but overall morbidity and mortality were not statistically different. Conclusions include that elective open heart surgery can be performed safely in ESRD patients using routine perioperative management.

The relationship of oxygen consumption measured by indirect calorimetry to oxygen delivery in critically ill patients.

OBJECTIVE: The existence of oxygen supply dependency, defined as oxygen consumption (VO2) limited by oxygen delivery (DO2), is still questioned. This study examined the relationship between VO2 and DO2 in two groups of critically ill surgical patients 50 years and older in the first 24 hours of resuscitation after pulmonary artery catheter insertion. Group 1 patients had systemic inflammatory response syndrome (SIRS), sepsis, severe sepsis, septic shock, and adult respiratory distress syndrome (ARDS). Group 2 patients had hemorrhagic shock. METHODOLOGY: Study methodology included (1) augmenting DO2 with fluids, blood, and vasopressors, (2) measuring VO2 by indirect calorimetry to avoid the problem of mathematical coupling with DO2 calculation, and (3) analyzing data during steady states of temperature, sedation, paralyzing agents, and vasopressors. RESULTS: Six to 18 measurements collected on all study patients during a period within the first 24 hours were analyzed using a linear regression analysis. Statistical significance was set at p < or = 0.05. Seven of nine patients in group 1 demonstrated positive, statistically significant relationships between VO2 and DO2. Of six patients in group 2, one patient demonstrated a positive, significant relationship of VO2 and DO2, three demonstrated inverse relationships, and two patients did not show a DO2/VO2 relationship. Supply dependency did not exist in all patients but was present in seven out of nine patients with systemic inflammatory response syndrome, sepsis, severe sepsis, septic shock, and adult respiratory distress syndrome in the first 24 hours of treatment.

Measurement of oxygen free radicals in a rabbit shock lung model. Effect of superoxide dismutase and retinol.

OBJECTIVES: To develop an isolated rabbit lung model in which oxygen free radical activity could be measured and to examine the effects on the model of oxygen free radical scavengers. DESIGN: Prospective, randomized study. SETTING: A clinical and basic research facility attached to a teaching hospital. PARTICIPANTS: Twenty-five New Zealand white rabbits weighing 3.5 to 4.5 kg. INTERVENTIONS: The mechanism of lung injury by oleic acid or by phorbol myristate acetate (20 ng/mL) plus polymorphonuclear neutrophils (PMA-PMN) in an ex vivo rabbit shock lung model may be the production of oxygen free radicals. Using a standard heart-lung preparation from these rabbits, baseline mean pulmonary artery pressure was maintained at 15 mm Hg and the mean airway pressure at 10 mm Hg. Experimental perfusates were infused over 30 minutes, followed by Krebs-Henseleit solution, pH 7.4. Dimethyl pyrroline oxide trapped oxygen free radicals, levels of which were measured by electron paramagnetic resonance spectroscopy. Lung injury was assessed by light and scanning electron microscopy and by lung weight. RESULTS: A 5-fold increase in pulmonary artery pressure (P < .001) and a nearly 3-fold increase in mean airway pressure (P < .001) were observed in both the oleic acid and PMA-PMN models. Superoxide dismutase (20,000 U/kg), but not retinol palmitate (2000 U), prevented lung injury, the increases in pulmonary artery pressure and mean airway pressure, and the increase in oxygen free radicals in the PMA-PMN model. There were no increases in oxygen free radicals in the control, oleic acid, or PMA-PMN/superoxide dismutase groups (n = 5 in each group). Maximum mean +/- SD increases in oxygen free radicals were 112 +/- 22 nmol/L in the PMA-PMN group (P < .003, n = 5) and 108 +/- nmol/L in the PMA-PMN/retinol group (P < .003, n = 5). CONCLUSIONS: The mechanism of lung injury in the PMA-PMN model is an increase in oxygen free radicals, because superoxide dismutase prevents both the rise in oxygen free radicals and lung injury. Administration of retinol does not prevent lung injury. Oleic acid produces injury not by an increase in oxygen free radicals but rather by another, unknown mechanism.

Surgical management of ventricular septal rupture following myocardial infarction: the Hawaii experience.

OBJECTIVE: To assess the diagnostic and treatment methods of ventricular septal rupture following myocardial infarction in a small patient population. EXPERIMENTAL DESIGN: Retrospective medical record review. SETTING: Four Honolulu area teaching hospitals. PATIENTS OR PARTICIPANTS: Eighteen patients with ventricular septal rupture (VSR) following myocardial infarction (MI) between 1979 and 1993. RESULTS: Ventricular septal rupture occurred more frequently in the elderly, in females and in those presenting for the first time with an MI. Thirteen patients (72%) underwent surgical repair including the two survivors. Three patients (17%) also underwent coronary artery bypass grafting, one of who survived. Very few of the patients had a history of stable angina pectoris before MI. Sudden deterioration in the patient's condition as manifested by tachycardia, hypotension and signs of right heart failure in those with an acute MI, especially if accompanied by a systolic murmur should encourage a search for a mechanical cause, especially a VSR. CONCLUSIONS: Two dimensional echocardiography or Swan-Ganz catheterization is 100% diagnostic and can be rapidly done at the bed side. Early surgical repair is important to the overall prognosis.

A repetitive DNA sequence specific for Trypanosoma (Nannomonas) godfreyi.

The satellite DNA sequence of Trypanosoma (Nannomonas) godfreyi, a recently described parasite of Suidae, was determined. The sequence is 373bp in length, and contains two imperfect internal repeats of approximately 170bp. Like other trypanosome satellite DNAs, it has no extensive open reading frames and is probably non-coding. There is no significant homology with other major repetitive DNAs within subgenus Nannomonas. We have developed a PCR test that is specific for T. godfreyi and used it to identify the parasite in natural tsetse infections from Zimbabwe and Côte d'Ivoire. This test shows no cross reaction with non-target trypanosomes, even within subgenus Nannomonas, and will be invaluable in studies of the prevalence and distribution of T. godfreyi.

An evaluation of streptokinase therapy in early coronary reperfusion in a primate model.

Efficacy of streptokinase (SK) administered beyond the period of coronary occlusion with regard to ultimate infarct size and the extent of hemorrhagic infarction was assessed in primates. Eleven macaques underwent coronary occlusion for two hours and were then reperfused. Five of them were given a 2,000 U IV bolus of SK followed by a 10,000 U IV infusion over ninety minutes. The remaining 6 served as controls. Macaques were sacrificed seven days postocclusion. The left ventricle was sectioned parallel to the minor axis, and these were examined histologically for infarct size and hemorrhage. Multiplying the planimetric values by the thickness of the sections yielded the total volumes of left ventricle, infarction, and hemorrhage. The mean percentage of left ventricle involved in infarction in the treated group was not significantly different from the controls (14.06 +/- 6.35 versus 16.50 +/- 4.67, P > 0.10). SK-treated animals had a significantly greater volume of infarct involved with hemorrhage as compared with controls (27.1 +/- 10.8 versus 4.0 +/- 1.4, P < 0.05). SK infusions done concurrently with reperfusion following a two-hour occlusion did not result in a significant reduction or increase in the size of infarct. However, SK infusions resulted in a significant increase in the amount of hemorrhagic infarction.

Distribution and abundance of trypanosome (subgenus Nannomonas) infections of the tsetse fly Glossina pallidipes in southern Africa.

Over 10 000 Glossina pallidipes tsetse flies were collected during two field studies in the Zambezi Valley, Zimbabwe and one in the Luangwa Valley, Zambia. These were screened for mature trypanosome infections and 234 dot-blot preparations were made of infected midguts, which were screened using DNA probes or PCR with primers specific to different species or types of the trypanosome subgenus Nannomonas. Over 70% of midgut infections were successfully identified as either Trypanosoma godfreyi, T. simiae or three types of T. congolense, savannah, riverine-forest and Kilifi. The relative abundance of species and types did not vary significantly between study locations, habitat, season or tsetse age or sex, although there were differences between DNA probe and PCR results. Mixed species and/or mixed type infections were common and were more often detected using PCR. The distribution of infections among flies was highly aggregated, but there was no tendency for multiple infections to accumulate in older flies, implying that sequential superinfection may be uncommon. Possible explanations for these patterns are discussed.

Failure to detect free radicals in the isolated perfused rat heart.

Oxygen free radicals have been indirectly implicated in reperfusion injury following ischemia in the isolated rabbit heart. The authors moved to detect free radicals in an isolated rat heart model as a prerequisite to studying its effects during ischemia and reperfusion. Several different spin trapping agents and electron paramagnetic resonance (EPR) spectroscopy were used to detect free radicals being generated during ischemia and reperfusion. The possible roles of ferrous iron and hydrogen peroxide generation in reperfusion injury were also investigated. No free radical "bursts" were detected with any of the spin traps used in this model during ischemia or reperfusion. Hydrogen peroxide and hydroxyl free radicals do not appear to be involved in tissue reperfusion injury. This study suggests that free radicals are not produced in clinically significant quantities under these conditions to account for ischemic myocardial damage.

A high prevalence of mixed trypanosome infections in tsetse flies in Sinfra, Côte d'Ivoire, detected by DNA amplification.

The prevalence of various species and subgroups of trypanosomes in the Sinfra area of Côte d'Ivoire was determined using the polymerase chain reaction (PCR). Using this technique to amplify specific satellite DNA targets, it was possible to identify developmental-stage trypanosomes in the midguts and the proboscides of tsetse without expansion of parasite populations. The predominant tsetse species in the area was Glossina palpalis, while G. pallicera and G. nigrofusca were also present. Microscopical examination of 811 non-teneral flies revealed an infection rate of 14% in midguts and/or proboscides. Three subgroups of Trypanosoma congolense (Savannah, Forest & Kilifi), T. simiae, T. godfreyi, West African T. vivax and T. brucei ssp. were identified using PCR. T. congolense Forest was the most abundant of the Nannomonas trypanosomes. Approximately 40% of all infections were mixed, and there was a significantly higher prevalence of apparently mature T. brucei ssp. trypanosomes than has previously been reported. The present study demonstrates that PCR facilitates the easy identification of mature trypanosome infections in tsetse, providing a reliable estimation of trypanosomiasis challenge.

International perspectives: USA/Hawaii.

Most of the factors that underlie Hawaii's current healthcare system were in place by 1950. Many of its healthcare features were shaped during the period from the eighth century AD until the revolution in 1893. Early chiefs made care available for the entire population through specially trained kahunas, or priests, who specialized in healing. There was a uniform, seamless healthcare system. The historical legacy, which came through from the early days, fostered the existence and acceptance of group and salaried practice by physicians, acceptance by employers of the responsibility to provide healthcare to workers, capitated payments to providers, focus on outpatient services, and historically short hospital lengths of stay. The success of Hawaii's system is rooted in its past. Whether other states could or should adopt Hawaii's system is conjectural. In Hawaii healthcare reform is not a new paradigm but rather an evolutionary phenomenon.