Cardiac Surgery in Nonagenarians

A bstract Objectives and Background : The purpose of this study was to document our initial experience with patients 90 years of age and older and to determine whether cardiac surgery is justified in this age group. Cardiac surgery in octogenarians has proven to be a successful and worthwhile procedure. A small group of nonagenarians with severe coronary artery disease (CAD) and aortic valve disease refractory to medical therapy have been considered for surgery. Methods : Fourteen patients aged 90 or more underwent cardiac surgery for symptomatic CAD or aortic valvular disease refractory to medical therapy. Eight patients underwent isolated coronary artery bypass grafting (CABG) and six patients underwent aortic valve replacement (AVR). All patients were in NYHA Class IV preoperatively. Results : Hospital mortality occurred in one patient (7%). Hospital morbidity occurred in 10 patients (71%) and included 7 cardiac, 5 neurological, 1 gastrointestinal, 1 infectious, and 1 pulmonary event. All survivors left the hospital symptomatically improved. The mean length of stay was 26 days. Four CABG patients went on to die at a mean of 2 years and 2 months, and 3 remain alive at a mean of 2 years and 4 months. Three AVR patients expired at a mean of 3 years and 4 months, and 3 remain alive at 4 years and 1 month. Conclusions : Cardiac surgery in carefully selected nonagenarians is justified and can be performed with acceptable results.     

Autologous blood transfusion for pediatric bone marrow donors.

Nine normal bone marrow donors aged 7-166 months (median 69 months) received autologous red cells which had been removed from their marrow harvest after collection. The median volume of marrow removed from the donors was 18.6 ml/kg which was equivalent to a median blood volume loss of 23.3%. Three infant donors were transfused with autologous red blood cells intraoperatively. These cells had been salvaged from the initial marrow aliquot and were transfused while bone marrow harvesting continued. No donors required homologous blood transfusion. This technique is useful for marrow donors in the pediatric age group when preharvest autologous blood collection is not feasible or available.     

Amyotrophic lateral sclerosis patient antibodies label Ca2+ channel α1 subunit

Sporadic amyotrophic lateral sclerosis is an idiopathic human degenerative disease of spinal cord and brain motor neurons. Prior studies demonstrated that most patients with amyotrophic lateral sclerosis posses immunoglobulins that bind to purified L-type voltage-gated calcium channels, that titers of anti–voltage-gated calcium channel antibodies correlate with disease progression rates, and that amyotrophic lateral sclerosis patient-derived antibodies (ALS IgG) produce electrophysiological changes in the function of voltage-gated calcium channels. Using Western transfer immunoblots and enzyme-linked immunosorbent assays, the calcium ionophore–forming α₁ subunig of the voltage-gated calcium channel is now identified as the major voltage-gated calcium channel antigen to which ALS IgG binds. Additionally, the binding of an L-type voltage-gated calcium channel α₁ subunit–directed monoclonal antibody, which itself mimics the effects of ALS IgG on skeletal muscle voltage-gated calcium channel currents, is selectively prevented by preaddition of ALS IgG. Voltage-gated calcium channel–binding IgG from patients with Lambert-Eaton myasthenic syndrome appears to be differentiated from ALS IgG by the reactivity of the former to both α₁ and β subunits of the calcium channel. These assays provide further evidence linking amyotrophic lateral sclerosis to an autoimmune process, and suggest one means to differentiate immunoglobulins from patients with amyotrophic lateral sclerosis from those of patients with another autoimmune disease expressing calcium channel antibodies.     

What do medical students seek to learn from general practice? A study of personal learning objectives.

With the aim of stimulating learning which is more self directed, fourth year medical students in Liverpool are encouraged to set personal learning objectives for the general practice attachment. On average, a student defines seven objectives for the three week attachment. A classification of objectives derived from the 1989 cohort of students is presented and the objectives could be seen as focusing on the practice population and its health problems, the role of the general practitioner, the work of general practice, the management of general practice, general practice as a career, and general learning. The validity and reliability of the classification are considered. Along with the advantages of this approach in motivating students to learn, the findings are considered in relation to impending changes in undergraduate medical education and the future role of general practice teaching by departments and by practice based colleagues.     

Chondral metaplasia in calcific insertional tendinopathy of the Achilles tendon.

OBJECTIVE: To ascertain whether tendon samples harvested from patients with calcific insertional Achilles tendinopathy showed features of failed healing response, and whether abnormal quantities of type II collagen had been produced in that area by these tenocytes. DESIGN: Comparative laboratory study. DESIGN: University teaching hospitals. PATIENTS: Tendon samples were harvested from eight otherwise healthy male individuals (average age 47.5+/-8.4 years, range 38 to 60) who were operated for calcific insertional Achilles tendinopathy and from nine male patients who died of cardiovascular events (mean age 63.1+/-10.9 years) while in hospital. INTERVENTIONS: Open surgery for calcific insertional Achilles tendinopathy. MAIN OUTCOME MEASURE: Semi-quantitative histochemical, immunohistochemical, and immunocytochemical methods to ascertain whether tendinopathic tendons were morphologically different from control tendons, and whether abnormal types of collagen were produced. RESULTS: Tenocytes from tendons from patients with calcific insertional Achilles tendinopathy exhibit chondral metaplasia, and produce abnormally high quantities of collagen type II and III. CONCLUSIONS: The altered production of collagen may be one reason for the histopathological alterations described in the present study. Areas of calcific insertional Achilles tendinopathy have been subjected to abnormal loads. These tendons may be less resistant to tensile forces. Further studies should investigate why some tendons undergo these changes.     

Cord insulin and C-peptide--distribution in an unselected population.

OBJECTIVE: To assess the distribution of cord blood insulin in an unselected population, and examine its relation to birthweight centiles. SETTING: District General Hospital in Nottinghamshire. SUBJECTS: 209 unselected singleton births. MEAN OUTCOME MEASURE: Cord blood insulin; cord blood C-peptide; birthweight centiles. RESULTS: Hyperinsulinaemic babies (greater than 97th centile for cord insulin) were found at all birthweight centiles. 15% of high birthweight babies were hyperinsulinaemic. For low birthweight babies, the distribution of cord insulin/C-peptide was skewed indicating a high number of low values. Hypoinsulinaemic babies were present up to the 50th centile for birthweight. CONCLUSIONS: Abnormalities of fetal insulinisation may be found in babies of all birthweights.     

Lethal Staphylococcus aureus-induced shock in primates: prevention of death with anti-TNF antibody.

A successful experimental treatment for gram-positive sepsis to our knowledge has not been achieved. The objectives of this study were to develop a nonhuman primate model of lethal gram-positive sepsis employing the micro-organism Staphylococcus aureus and to determine the efficacy of treatment using monoclonal antibody (MAb) to tumor necrosis factor alpha (TNF). The antibody was administered intravenously, 15 mg/kg, 30 minutes after the beginning of a 2-hour infusion of S. aureus, 4 x 10(10) colony forming units/kilogram. The baboons infused with S. aureus demonstrated the release of the cytokines TNF and interleukin-6 (IL-6), but endotoxin was not observed in the plasma at any time. Treatment with antibody to TNF abolished the rise in serum TNF levels and reduced the increased levels of IL-6. Treatment with MAb to TNF prevented multiple organ failure and achieved permanent (> 7 day) survival of all baboons.     

Stabilization of acetylcholine receptors at the neuromuscular synapse: the role of the nerve.

The majority of acetylcholine receptors (AChRs) at innervated neuromuscular junctions (NMJs) are stable, with half-lives averaging about 11 days in rodent muscles. In addition to the stable AChRs, approximately 18% of AChRs at these innervated junctions are rapidly turned over (RTOs), with half lives of less than 24 h. We have postulated that RTOs may be precursors of stable AChRs, and that the motor nerve may influence their stabilization. This hypothesis was tested by: (i) labeling AChRs in mouse sternomastoid (SM) muscles with 125I-alpha-BuTx; (ii) denervating one SM muscle in each mouse, and (iii) following the fate of the labeled AChRs through a 5-day period when RTOs were either stabilized or degraded. The hypothesis predicts that denervation should preclude stabilization of RTOs, resulting in a deficit of stable AChRs in denervated muscles. The results showed a highly significant (P less than 0.002) deficit of stable AChRs in denervated as compared with innervated muscles. Control experiments excluded the possibility that this deficit could be attributed to independent accelerated degradation of either RTOs or pre-existing stable AChRs. The observed deficit was quantitatively consistent with the deficit predicted by a mathematical model based on interruption of stabilization following denervation. We conclude that: (i) the observed deficit after denervation of NMJs is due to failure of stabilization of pre-existing RTOs; (ii) RTOs at normally innervated NMJs are precursors of stable AChRs; (iii) stabilization occurs after the insertion of AChRs at NMJs, and (iv) motor nerves play a key role in stabilization of RTOs. The concept of receptor stabilization has important implications for understanding the biology of the neuromuscular junction and post-synaptic plasticity.