Relation of therapeutic response to nifedipine to coronary anatomy and motion of S-T segment during unstable angina pectoris

Of 77 patients hospitalized for unstable angina pectoris and failure of oral, dermal, or intravenous nitrates and/or beta blockade, 81 percent with negligible or single-vessel disease and 55 percent with two- or three-vessel disease showed response (p < 0.05) to nifedipine therapy. Patients with either S-T elevation or no change during pain responded better (31 of 45) than those with any S-T depression (16 of 32; p < 0.05). Patients with negligible or singlevessel disease had a higher prevalence of S-T elevation ( 13 of 16) than patients with two- or three-vessel disease (15 of 31; p = 0.004). S-T motion did not predict response in patients with two- or three-vessel disease, but did predict response in patients with negligible or single-vessel disease. On follow-up study at 9 ± 8 (range one to 33) months, 39 of 42 who had shown response were free from pain. Three died from infarction without unstable angina. Five who showed response had elective bypass surgery. The addition of nifedipine abolished or reduced pain episodes by more than 50 percent in 61 percent of patients with refractory unstable angina pectoris. Patients with negligible or single-vessel disease with S-T elevation benefit most. In patients with two- or three-vessel disease, the type of S-T motion did not predict response. Follow-up of all those with response indicated sustained amelioration by nifedipine therapy. Failure of nifedipine therapy should not be accepted until a dose of 120 mg per day has been achieved, or until intolerable side effects appear.     

Campylobacteriosis in man: Pathogenic mechanisms and review of 91 bloodstream infections

Five patients with Campylobacter fetus (previously called “Vibrio fetus”) bacteremia are presented with enteric symptoms in four patients, a self-limited course in three, and with possible nosocomial infection in one patient who had disseminated malignancy. The clinical syndromes of 91 bacteremic patients with campylobacteriosis and C. fetus taxonomy and pathogenicity are reviewed.Studies of potential pathogenic mechanisms in enteric infections failed to reveal the production of either heat-stable or heat-labile, cholera-like enterotoxin, cytotoxicity or invasiveness. In comparison with different species of vibrio infections, C. fetus appears to produce disease by a different mechanism, one which involves a bloodstream infection, perhaps following penetration through the intestinal mucosa as has been demonstrated experimentally with salmonellae and yersinia. Such a pattern is consistent with the clinical pattern of C. fetus infections and the experimental studies reported herein.     

Double-blind randomized study of prophylactic trimethoprim/sulfamethoxazole in granulocytopenic patients with hematologic malignancies

In a double blind study, oral prophylactic trimethoprim/sulfamethoxazole was evaluated for its utility in preventing serious infections in patients with hematologic malignancy. Of 58 evaluated granulocytopenic episodes in 47 patients, acute leukemia was the underlying malignancy in 46 episodes. Trimethoprim/sulfamethoxazole prophylaxis resulted in fewer microbiologically documented infections (seven versus 15; p = 0.029). This was primarily the result of a reduction in episodes of bacteremia in the trimethoprim/sulfamethoxazole-treated group as compared with the placebo-treated group (three versus nine episodes; p = 0.05). The combined frequency of disseminated candidiasis, candidemia, and esophagitis of presumed fungal etiology was greater in the trimethoprim/sulfamethoxazole-treated group (six) than in the placebo-treated group (two) but not significantly so (p = 0.13). Similarly, there were no significant differences between groups in the overall incidence of infectious complications, number of febrile days, use of parenteral antibiotics, or number of days following randomization to first infectious episode. Throat and rectal surveillance cultures more frequently revealed trimethoprim/sulfamethoxazole-resistant gramnegative bacilli and yeasts in the trimethoprim/sulfamethoxazole-treated group. More frequent emergence of yeast isolates from previously culture-negative patients was documented (p = 0.033). Thus, in this study, trimethoprim/sulfamethoxazole prophylaxis during granulocytopenia reduced the incidence of microbiologically documented infections. However, the emergence of resistant bacteria and of fungi may limit the potential usefulness of this approach.     

Reduction of prehospital,ambulance and community coronary death rates by the community-wide emergency cardiac care system

Initiation of quick prehospital cardiopulmonary resuscitation and emergency cardiac care completed the total system needed to provide emergency and convalescent coronary care for a community. Subsequently, annual community rates for coronary death during ambulance transport fell by 62 per cent and for prehospital coronary death by 26 per cent in people under 70 years of age. In cardiac arrest due to acute myocardial infarction, prompt successful prehospital correction of ventricular fibrillation and asystole yielded long-term survival in two thirds of cases. This 66 per cent success rate of prehospital cardiopulmonary resuscitation and emergency cardiac care is identical to contemporary international experience. Precordial thump-version with the fist and precordial fist pacing appeared logical additions to prehospital cardiopulmonary resuscitation and emergency cardiac care technics. Community lives saved yearly were $\text{15.2}\text{100,000}$ people aged 30 to 69 years and $\text{6.4}\text{100,000}$ total population. Simultaneously, annual community rates for coronary death as a cause of death and coronary death per 1,000 people fell significantly by 15 and 17 per cent, respectively. Unquantifiable influences included prehospital relief of ischemic chest pain; prehospital correction of acute dysautonomia; prehospital abolition of otherwise prefatal dysrhythmias; similar treatment for acute myocardial infarction in the emergency department, in the inhospital mobile coronary care unit and in the progressive intermediate coronary convalescent unit; and general community education through the media of newspapers, radio and television. The present frequency of coronary death during ambulance transport, 9 to 22 per cent of prehospital coronary deaths in this and other surveys, suggests that the prehospital cardiopulmonary resuscitation and emergency cardiac care component needs improvement in many communities. By reducing prehospital and ambulance coronary death rates, prehospital cardiopulmonary resuscitation and emergency cardiac care for acute myocardial infarction constitutes an essential component of the total system approach to emergency coronary care. Since prehospital cardiopulmonary resuscitation and emergency cardiac care have cheaply and effectively expedited and abbreviated hospitalization for acute myocardial infarction, and lowered community death rates from coronary artery disease, its adoption throughout the United States and the western world seems justified.     

Determinants of glucose and ketoacid concentrations in acutely hyperglycemic diabetic patients

Diabetic hyperosmolar coma is a syndrome of marked hyperglycemia and minimal ketoacidosis. In general, the serum glucose concentrations are not predictive of the serum ketoacid concentrations in acutely decompensated diabetes. The endocrine factors that modulate glucose concentrations may be different from those that modulate ketoacid concentrations in patients with acutely decompensated diabetes. To test this hypothesis, regression analysis was used to determine the endocrine and metabolic characteristics that correlated with serum concentrations of glucose and ketoacids in 26 diabetic patients with spontaneous, acute hyperglycemia. All patients had a serum glucose level greater than 390 mg/dl, and ketoacid levels were from 0.17 to 25.5 mM. Multiple regression analysis showed that increased serum glucose concentrations correlated with increased plasma glucagon levels (p = 0.0007, r2 = 0.45), but with no other factors. Increased total ketoacid levels (acetoacetate plus 3-hydroxybutyrate) correlated with increased free fatty acid levels (p = 0.0001), decreased C-peptide levels (p = 0.002), and increased body mass index (p = 0.002) (r2 = 0.72). Body mass index only correlated with ketoacid levels, when it was analyzed with C-peptide and free fatty acid levels. A model is proposed that predicts the serum glucose and ketoacid concentrations in patients with acutely decompensated diabetes. Glucagon modulates the serum glucose concentration in these patients with an absolute or relative insulin deficiency. Total serum ketoacid levels are determined by the serum free fatty acid concentration, residual pancreatic insulin secretion (as reflected by C-peptide), and the patient's body habitus. This model allows for the marked hyperglycemia and minimal ketosis of diabetic nonketotic hyperosmolar coma, as well as the glucose and ketoacid concentrations in other presentations of acutely decompensated diabetes.     

Value of laboratory tests in the differential diagnosis of hypercalcemia

Eighteen laboratory tests were compared in the differentiation of primary hyperparathyroidism from hypercalcemia associated with malignancy. Statistical comparisons of the test results were carried out in four patient groups and two control groups. The patient groups evaluated were those with confirmed primary hyperparathyroidism, those with malignancy with hypercalcemia, those with malignancy without hypercalcemia, and those with surgically cured primary hyperparathyroidism. These groups allowed determination of the relative diagnostic values of the tests and a rationale for their value. After exclusion of patients with renal failure from the patient and control groups, these data indicated that the laboratory tests with the greatest differential diagnostic value, in order of efficacy, were: albumin, carboxy-terminal parathyroid hormone, venous pH, cholesterol, chloride, alkaline phosphatase, phosphorus, and the chloride/phosphate ratio. Hemoglobin, hematocrit, and red blood cell count also had some value, particularly in male patients. However, none of these tests individually achieved better than an 81 percent classification accuracy. With application of logistic discriminant analysis, only three tests--albumin, parathyroid hormone, and chloride--were identified as statistically significant in jointly improving the diagnostic separation between these two patient groups. Although the 94.4 percent classification accuracy achieved by use of these three variables in a logistic discriminant function was better than that obtained with any individual variable, incorrect classification was still a significant problem, particularly in the case of patients with malignancy and high concentrations of parathyroid hormone. With the exception of albumin and chloride measurements, the commonly available ancillary laboratory tests proposed to aid this differential diagnosis do not give any more information than the analysis of parathyroid hormone alone and merely add to the increased cost of medical care.     

Identification and differentiation of surgically correctable hypertension due to primary aldosteronism.

During a protocol study for the evaluation of patients with primary aldosteronism, a variety of diagnostic studies were employed in an attempt to identify patients with primary aldosteronism and to differentiate patients with adrenal adenoma from patients with idiopathic adrenal hyperplasia. In this study, we are able to demonstrate the utility of (1) absent postural increase in plasma aldosterone concentration, (2) adrenal scanning and (3) normalization of blood pressure with spironolactone therapy in identifying patients with primary aldosterone excess who have an adrenal adenoma, surgical removal of which results in eliminating their hypertension.     

An evaluation of diabetic and pseudodiabetic glomerulosclerosis.

Diabetic glomerulosclerosis must be either a primary manifestation or a secondary consequence of the metabolic abnormalities of diabetes. Several earlier reports have attempted to support the former hypothesis by describing cases of pathognomonic renal lesions in nondiabetic subjects; however, the clinical and pathologic data in these reports are inconclusive. We have reviewed our experience at the University of Virginia Hospital with 447 percutaneous renal biopsies performed over a period of four years from July 1973 through July 1977. Of these cases, only two appeared to represent diabetic glomerulosclerosis occurring in nondiabetic subjects. Upon further investigation, one case provided to be light chain disease demonstrated by immunofluorescence staining. The other case, on repeat renal biopsy, proved to be membranoproliferative glomerulonephritis. We conclude that a diagnosis of diabetic glomerulosclerosis must be viewed with suspicion in nondiabetic subjects. Suspected cases should be labeled pseudodiabetic glomerulosclerosis and investigated further.     

Strychnine poisoning. Recovery from profound lactic acidosis, hyperthermia, and rhabdomyolysis

Strychnine poisoning results in a predictable and treatable sequence of events involving blockade of the inhibitory neurotransmitter, extensor muscle spasms, seizures, and respiratory paralysis. These spasms may lead to hyperthermia, profound lactic acidosis, and rhabdomyolysis. Acidosis is primarily attributable to lactate, as indicated by the correlation between arterial pH and log of lactic acid concentration (r = -0.878). Interruption of the strychnine blockade is the primary therapy for strychnine poisoning. Phenobarbital in moderate doses should be the first intervention and anesthetic doses should be used if necessary. Suppression of convulsions will permit successful management of the complications of strychnine poisoning. Our patient survived, even though at one point he had a pH of 6.55, a lactate level of 32 mM/liter, a temperature of 43 degrees C, and rhabdomyolysis with an increased creatine phosphokinase level of 359,000 mU/ml (5,983 mumol/s/liter).     

Invasive aspergillosis of the lung and pericardium in a nonimmunocompromised 33 year old man

In a 33 year old man with no discernible immunologic defect, invasive aspergillosis developed in both the pericardium and lung with marked granulomatous reaction. The patient received 2 g of intravenous amphotericin B over eight weeks, with partial regression of the pulmonary infiltrate and disappearance of symptoms. However, five months later, he returned with marked progression of his disease. Evaluation of host defense, including granulocyte and lymphocyte function, was normal. The patient was given an additional 3 g of amphotericin B over nine weeks with marked improvement in symptoms and chest roentgenogram. At six-month follow-up, he was asymptomatic with a stable radiographic appearance. A recurrence in symptoms and the pulmonary infiltrate was noted two months later. He was treated with an additional course of amphotericin and currently is receiving ketoconazole in hopes of suppressing the infection. We could find no immune impairment to explain the severe pulmonary and pericardial disease due to Aspergillus flavus in this young man.     

Peripheral neuropathy presenting with respiratory insufficiency as the primary complaint. Problem of recognizing alveolar hypoventilation due to neuromuscular disorders

A 57 year old farmer, initially believed to have hypoventilation secondary to medullary respiratory insensitivity, died with a peripheral neuropathy and marked involvement of the phrenic nerves. Peripheral neuropathy has not previously been reported to present in this manner. Routine pulmonary function tests that would help to distinguish patients with hypoventilation due to neuromuscular disorders from patients with hypoventilation due to diseases of the lung parenchyma and depression of the medullary respiratory centers were investigated. Five subjects with severe neuromuscular disease were studied (arterial carbon dioxide tension [pCO₂]48 to 69 mm Hg, vital capacity [VC] 13 to 79 per cent of predicted and 1 second forced expiratory volume [FEV₁] 76 to 96 per cent of VC). The mean ratio of maximum mid-inspiratory flow (MMIF) to maximum mid-expiratory flow (MMEF) was 0.79. In age-matched control subjects this ratio was 1.41. In addition to observing the ratio of MMIF to MMEF other effective clinical screening procedures to distinguish patients with hypoventilation secondary to neuromuscular disorders from patients with medullary respiratory insensitivity include (1) identification of weakness of the muscles used for ventilation by measuring the static maximum inspiratory and expiratory airway pressures, (2) determination of ability to lower the arterial pCO₂ with voluntary hyperventilation, and (3) comparison of the maximum breathing capacity to the minute ventilation while breathing 7.5 per cent carbon dioxide for 3 minutes. The latter two measurements permit assessment of central hypoventilation in the presence of intrinsic lung disease.     

Rapidly progressive silicon nephropathy

Rapidly progressive renal failure developed in four patients with silica exposure. Three presented with manifestations of a connective tissue disorder. All had abnormal proteinuria, hypoalbuminemia and active urinary sediments. Histologically, a distinct constellation of findings was present, consisting of glomerular hypercellularity and sclerosis, crescents, interstitial cellular infiltrates and tubular necrosis with red cell casts as seen on light microscopy. On electron microscopy there was foot process obliteration, characteristic cytoplasmic dense lysosomes, microtubules and dense deposits. Despite vigorous treatment, two patients died of the systemic illness and one is on hemodialysis. The fourth is improved after pulse methylprednisolone therapy. We propose that silica induced this multisystem disease through activation of the immune system and a direct tissue toxic effect.     

Cell wall-deficient bacterial variant cultural surveillance. A useful laboratory aid.

A cell wall-deficient variant of Corynebacterium species was isolated from the blood of a patient with a chronic febrille illness of unkown etiology. He was given antimicrobial therapy, to which both variant and reverted bacterial forms of this organism were sensitive, and he recovered. Cultural surveillance for cell wall-deficient organisms was not only helpful in confirming the presence of infection in our patient but also in following his clinical course once antimicrobial therapy had been instituted.     

Lung biopsy in immunocompromised hosts.

Ninety-five lung biopsy procedures in 78 immunocompromised patients yielded treatable diagnoses in 35 per cent of the needle aspirates, 46 per cent of the cutting needle biopsies and 65 per cent of the open thoracotomies. Complication rates of bleeding or pneumothorax were comparable to those previously described in nonimmunocompromised patients. In patients with coagulation defects, the risk of having bleeding complications was high. Among 44 patients with primary lymphoma, 22 (50 per cent) had a lymphomatous infiltrate in the lung. Twenty-two patients with severe hypoxemia were studied and their mortality, although significantly greater than in the patients without hypoxemia, was marginally improved when a treatable lung lesion was found. The over-all recovery rate was 70 per cent when a treatable diagnosis was made in contrast to 25 per cent when there was no specific diagnosis. Hence lung biopsy, particularly by thoracotomy, appears to be a valuable procedure in immunocompromised patients who have otherwise undiagnosable lung lesions.     

Staphylococcus aureus bacteremia. Current clinical patterns.

One hundred and five cases of bacteremia due to Staphylococcus aureus were reviewed to assess the current clinical spectrum of serious staphylococcal disease. Mortality was 21 percent, lower than previously reported. Patients could be separated into two groups according to the presence of identifiable primary staphylococcal infections; 63 bacteremic patients had such lesions, the remaining 42 lacked them. The latter group contained 24 of 26 cases of endocarditis. Illnesses in that group were marked by the presence (in 38 of 42 patients) of staphylococcal foci occurring secondary to bacteremia. Such foci were responsible for five of seven instances of relapse or treatment failure encountered in that group. Secondary staphylococcal foci occurred in only five of 63 patients with primary infections, and the response of this group to conventional therapy for bacteremia was satisfactory. This study suggests that endocarditis has become an unusual complication of identifiable primary staphylococcal infection. A clinical classification based on the presence of such lesions therefore separates bacteremic patients likely to be cured by conventional antibiotic therapy (those with primary infections but no secondary foci) from others (those with secondary foci, suggesting endocarditis) who should receive a more prolonged course of antibiotics.     

Fatal disseminated adenovirus infection in a renal transplant recipient.

A 61 year old woman died of diffuse interstitial adenovirus pneumonia 55 days after receiving a cadaveric renal allograft. The adenovirus was serologically distinct from the 33 known human adenovirus serotypes and appears to represent a new human adenovirus. Pathologic and virological findings indicate that the pneumonia was only one manifestation of a disseminated infection, the source of which may have been a latent adenovirus infection preexisting in the donor kidney. The establishment of the etiologic diagnosis in this case, which was complicated by the presence of oculocutaneous and esophageal herpes simplex virus infection as well as focal pulmonary aspergillosis, required coordinated histopathologic and virological investigation. Our findings demonstrate that severe viral infections in transplant recipients are not caused exclusively by members of the herpesvirus group.     

Double myeloma. Production of both IgG type lambda and IgA type lambda myeloma proteins by a single plasma cell line

Monoclonal immunoglobulins G (IgG) and A (IgA) of the lambda light chain type were present in the serum of a patient with multiple myeloma. Three populations of myeloma cells were seen by immunofluorescence of bone marrow; those containing either IgG or IgA and those staining for both IgG and IgA. Idiotypic determinants present on the variable regions of the two myeloma proteins were immunologically identical and all the myeloma cells contained the same idiotypic determinant. The idiotypic specificity was related more closely to the variable region of the heavy chain than to the light chain. Structural and electrophoretic analysis confirmed that the light chains of the two myeloma proteins were identical. The myeloma in this patient appears to have arisen from a single clone of cells that was capable of synthesizing the constant portions of both the IgG and IgA heavy chain but only a single light and heavy chain variable region. These findings suggest that current concepts of antibody synthesis involving the sequential production of immunoglobulin M (IgM) and IgG antibodies may apply to certain cell lines synthesizing IgG and IgA antibodies as well.