Nephropathia epidemica: mild variant of hemorrhagic fever with renal syndrome.

The diagnosis of nephropathia epidemica (NE) is primarily not histological, but because biopsy samples sometimes reach the pathologist, knowledge of histology may be of diagnostic value, in addition to clarifying the pathogenesis. The authors collected 80 biopsies from 65 patients taken after the onset of NE from various hospital files in Finland. Light microscopic, morphometric, electron microscopic, and immunohistochemical methods were applied in studying these samples. There was slight tubular dilatation and interstitial edema best evidenced during the first month after the onset of the disease. There was limited electron microscopic evidence of endothelial cell damage or reaction, also in the glomeruli. Occasional tubular necrotic cells or mitoses were found. About half of the cases were positive for IgG or IgM, and C3 and fibrin in the tubular basement membrane. Samples of the recovery phase showed interstitial fibrosis. Medullary interstitial hemorrhages were seen in 60% of samples of the first two weeks after onset. Interstitial inflammatory changes were diffuse in the early phases and often focal thereafter. During the first two weeks there was congestion and mild hypercellularity of the glomeruli. There was also slight prominence of mesangium, and evidence of endothelial cell damage or reaction. Osmiophilic glomerular deposits were scanty. Focal immunoglobulin (usually IgG) and complement deposits were present in the glomeruli, but less intense than in classical glomerulonephritis. Without medullary hemorrhages in the biopsy, the suggestive diagnosis could rest on interstitial edema, diffuse but sparse inflammatory infiltrate, dilatation of occasional tubules, changes suggestive of tubular cell death, and congestion and slight hypercellularity of the glomeruli.

Pharmacokinetic comparison of a dextromethorphan-salbutamol combination tablet and a plain dextromethorphan tablet.

We compared in this double-blind crossover study the bioavailability of dextromethorphan from a dextromethorphan-salbutamol combination tablet (Redol comp) and from a plain dextromethorphan tablet (Extuson) by determining dextrorphan concentrations after single-dose oral administration in 10 healthy volunteers. The absorption of salbutamol from the combined preparation was also determined. The absorption of dextromethorphan was slightly faster from the plain dextromethorphan preparation. The peak concentration of dextrorphan was achieved at 1.5 h after Extuson and at 2 h after Redol comp (1,053.0 +/- 366.5 ng/ml and 901.5 +/- 210.9 ng/ml, NS). AUC0-12 values of dextrorphan were 4,315.6 +/- 295.0 (ng/ml)h after Extuson and 3,983.8 +/- 205.6 (ng/ml)h after Redol comp (p less than 0.05). Salbutamol was well absorbed from the combined preparation and the peak concentration was achieved at 3 h (6.57 +/- 2.95 ng/ml). Four subjects reported side-effects typical for salbutamol after the combination tablet. No side-effects were reported after the plain dextromethorphan tablet. On the basis of the present study, we conclude that the absorption of dextromethorphan from the preparations tested is almost equal and the dextromethorphan-salbutamol combination can be administered in tablet form for the treatment of cough.

Morphometric study of human myocardium in acquired valvular diseases.

To study the effect of various valvular heart diseases on the quantitative histology of myocardium, 38 human hearts with valvular lesions were examined (11 aortic stenoses, nine mitral stenoses, nine mitral incompetence and nine combined aortic and mitral valve lesions). The control group consisted of ten hearts without any valvular lesions. With morphometrical methods the volume fractions of myocardial components (myocardial fibres, interstitial space and diffuse connective tissue), the numerical density of arterioles and the mean fibre diameter were estimated. Myocardial fibrosis was more severe in hearts with valvular lesions than in the controls (5.4% vs 3.3%, P less than 0.01), but did not correlate with the anatomical severity of the valvular lesions. The most severe myocardial fibrosis was found in hearts with mitral incompetence (6.7%). Fibre hypertrophy was most severe in hearts with aortic stenosis and in hearts with mitral incompetence (22 microns and 23 microns, respectively). In hearts with severe valvular lesions the mean fibre diameter was 23 microns and in hearts with mild to moderate lesions 19 microns (P less than 0.01). Good correlation was observed between the mean fibre diameter and the weight of the left ventricle (r = 0.81, P less than 0.01). The volume fractions of connective tissue and interstitial space were significantly higher and the volume fraction of myocardial fibres was correspondingly lower in the subendocardium than in the subepicardium in hearts with either pressure overload (aortic stenosis) or volume overload (mitral incompetence). In conclusion, myocardial fibrosis occurs in patients with various valvular lesions, but the severity of the fibrosis does not correlate with the anatomical severity of valvular lesions.(ABSTRACT TRUNCATED AT 250 WORDS)

Thymus-dependent immune functions in chickens bursectomized with colchicine applied to the anal lips.

Thymus-dependent immune functions were investigated in chickens bursectomized neonatally with colchicine solution given per anum. Antibody responses to thymus-dependent antigens sheep red blood cells (SRBC) and human gamma-globulin (HGG) were delayed, reaching the normal level after the third antigen stimulation. Also the mitogenic responses of peripheral blood lymphocytes were preserved, and no changes in the thymic morphology were found. In contrast, antibody responses to bursa-dependent antigen Brucella abortus were low and the switch of immunoglobulin isotypes from IgM to IgA and IgG was disturbed. It can be concluded that neonatal bursectomy with cloacal administration of colchicine does not significantly affect T cell functions, whereas B cell functions are partially deficient.

Ischemic heart disease and heart weight.

Separate weights for heart ventricle walls and interventricular septa were analyzed in 110 hearts with autopsy findings of ischemic heart disease (coronary atherosclerosis, recent or old myocardial infarcts) and with no other cardiac or systemic causes of cardiac enlargement. In hearts with coronary atherosclerosis alone (without old or recent myocardial infarcts) no weight increase was observed in the left ventricle when compared to 29 controls. Patients having infarcts associated with nonstenosing atherosclerosis (less than 50% of the luminal diameter narrowed) of the coronaries had normal heart weights as well. On the contrary, infarcts associated with stenosing coronary sclerosis (narrowing more than 50%) showed significant signs of left ventricular weight increase, which is interpreted as compensatory heart hypertrophy. The greatest degree of hypertrophy was observed in hearts with left ventricular aneurysms.

Postembryonic development of the chicken bursa of Fabricius: a light microscopic histoquantitative study.

Development of the bursa of Fabricius in the chicken was studied from day 4 to day 84 after hatching using light microscopic, morphometric methods. The proportion of lymphoid follicles of the total bursal tissue increased from 62% at day 4 to 86% at day 63 and thereafter decreased slightly until day 84. The corresponding values for bursal stroma and epithelium decreased from day 4 to day 84. The relative and absolute amounts of lymphoid tissue increased from enlargement of individual lymphoid follicles; their mean spatial diameter increased from 185 microns at day 4 to 720 microns at day 84. The number of areas of follicle-associated epithelium at the bursal mucosa, which in a mature bursa corresponds to the follicle number, remained relatively unchanged (range 7200 to 12000 per bursa). the follicular cortex grew more rapidly than did the follicular medulla, indicating different functions for each. The total surface area of the follicle-associated epithelium was .88 cm2 at day 4 increasing to 4.71 cm2 at day 63. This increase also in mainly due to increased size of the individual areas of follicle-associated epithelium (diameter increased from 71 to 168 microns). Histoquantitative findings are discussed in light of present knowledge about the function of the bursa as a central and peripheral lymphoid organ.

Testosterone action on the ventral prostate lobe of the castrated rat as assessed with a stereologic morphometric method.

The effects of testosterone (1 mg testosterone propionate/100 g body weight for 30 days) on the ventral prostates of rats castrated 30 days prior to the onset of hormone treatment was investigated with a stereologic morphometric method. Testosterone induced rapid growth of the prostate, which was reflected by a 29-fold increase in acinar parenchyma but only a 2.6-fold increase in interacinar tissue. There was a 23-fold increase in the total amount of glandular epithelium and a 36-fold increase in total luminal amount. Various volumetric fractions, total surface area, total tubule length, height of the epithelium, mean diameter of the tubules, and mean distance between the tubules and between the glandular centers were calculated. Growth of the acinar parenchyma, especially of the glandular lumen, was the dominant pattern. We could not demonstrate any remarkable responses in the interacinar tissue during any phase of testosterone treatment.

Trauma, renal vein thrombosis and subsequent nephrotic syndrome.

A case of kidney trauma with local and systemic consequences is given. The patient got a trauma to right kidney region. After a fortnights latency nephrotic syndrome developed. Radiological examinations one month after the trauma revealed a partially recanalized thrombus in the right renal vein. It turned out in renal biopsy that the underlying cause of the nephrotic syndrome was acute proliferative glomerulonephritis with typical humps in electronmicroscopy. In contralateral (non-traumatized) kidney there was in renal biopsy the same type of acute glomerulonephritis as well. The course of the renal lesion was documented by a series of renal biopsies which showed improving proliferative glomerulonephritis. The time course of the events and the bilateral histological changes suggest renal trauma as the cause of acute proliferative glomerulonephritis which is a new aspect.

Bone and bone-marrow blood flow in chronic granulocytic leukemia and primary myelofibrosis.

Blood flow in hematopoietic bone marrow and in nonhematopoietic bone has been measured with a Xe-133 washout method in 20 patients with chronic granulocytic leukemia (CGL) and in seven with primary myelofibrosis. Age-matched healthy persons served as controls. Bone-marrow blood flow in CGL was dependent upon the phase of the disease. In the metamorphosis phase, bone-marrow blood flow was high compared with that in the well-controlled phase. Apart from the initial phase, the mean values for bone blood flow in CGL were increased compared with the values of the healthy controls. In myelofibrosis the bone blood flow was also increased. Bone-marrow blood flow in these diseases was dependent upon the cellularity of bone marrow as measured morphometrically.

In-hospital death from ischaemic heart disease.

The clinical course and the clinical and pathological factors were studied in a series of 112 in-hospital patients who died of acute myocardial infarction. A necropsy was performed in 101 cases. 44% of the victims were concluded to have been past the possibility of recovery at the time of admission, as the treatment of early ventricular fibrillation or asystole did not lead to a satisfactory result, or as a refractory heart failure or shock dominated from admission to death. Resuscitations due to early ventricular fibrillation were performed in the emergency department mainly on patients living near the hospital. On the other hand, an early heart failure was more frequent among those whose transit distance was over 15 km. Prior use of beta-receptor blockers seemed to protect against early complications. The cardiac functions of the remaining patients were normal or could be normalized at the beginning of the hospitalization. The great majority of them were later lost as a result of extensive damage of the myocardium leading to a refractory heart failure and some due to a rupture caused by infarction (8%) or due to embolic complications (10%). Only 11 patients (10%) succumbed to late ventricular fibrillation without heart failure, rupture, or embolism. The cardiac disease revealed by the necropsy was more severe in patients with a refractory heart failure than in those who died of late ventricular fibrillation or rupture without a preceding heart failure. Various arrhythmias were frequent during the hospitalization. 74% of the dysrhythmias were preceded or followed by symptoms of a heart failure.

Early pronounced ST segment depression with marked J point decline heralding acute lethal clinical myocardial infarction: Necropsy-electrocardiographic correlative study.

Marked ST segment depression (greater than or equal to 2 mm J point decline with horizontal or downsloping ST) was correlated with necropsy findings in 105 cases. Acute myocardial infarction (AMI) was most frequently (70%) responsible for development of the abnormal ST pattern, thereby indicating the diagnosis and severe prognosis of the AMI. In 23% of patients the ST segment depression pattern was associated with chronic heart disease without AMI; all were severely ill with 92% receiving digitalis. Sudden worsening of the basic heart disease or circulatory shock were frequently found to coincide with the abnormal ST pattern; necropsy revealed extensive old MI or myocardial fibrosis in these patients. Marked ST segment depression was also found in five patients without underlying heart disease at autopsy; an acute cerebral accident or circulatory shock was considered to have produced the abnormal ST segment pattern.

The effect of age on blood flow in the proximal femur in man.

blood flow in the proximal femur was measured in 45 healthy male and female adults by means of a Xe-133 washout method. On the basis of a two-compartment exponential model, blood flow was calculated assuming that the compartments were hematopoietic (red) marrow and nonhematopoietic tissues of bone. Between the ages of 20 and 55 the bone perfusion was 8.3 +/- 1.4 (1 s.d.) ml/100 g/min, decreasing thereafter in older patients. During the same period the red-marrow blood flow (RMBF) decreased linearly: RMBF (ml/100 g/min) = -0.14 x age + 24.5. The nonhematopoietic bone perfusion changed like the bone perfusion. The fractional masses of red marrow and nonhematopoietic tissues of bone in the greater trochanteric region of the femur were determined morphometrically from the bone biopsies of seven adult cadavers. They agreed with the values estimated by the Xe-133 washout method. The blood-flow values will be used as reference values for the Xe-133 bone circulation method.

Verrucous squamous cell carcinoma of the female genital tract. Report of three cases and survey of the literature.

Three new cases of gynecological verrucous squamous cell carcinomas are reported; one in the uterine cervix, and two in the vulva. The English literature covering the 49 cases reported previously is surveyed with special reference to the diagnostic and therapeutic aspects of these tumors, as well as with their clinical behavior and possible relationship to viral (HPV) lesions (Condylomas) of the genital tract. It was concluded that so far the exact relationship between the different verrucous squamous cell lesions in the genital tract remains obscure, all such lesions should be regarded as potentially malignant, and treated accordingly by radical surgery.

A morphometrical method for analyzing germinal centers in the chicken spleen.

A morphometric method for the analysis of the germinal centers in the chicken spleen is presented. Based on counts in the two-dimensional tissue sections, the following three-dimensional germinal center characteristics were calculated: volume density (VVgc); numerical density (NVgc); total number in the spleen (Ngcsp); nearest neighbour distance (delta 3), and mean diameter (D). The total number of the germinal centers in the spleen of the six-week-old and the ten-week-old unimmunized chickens was 803 and 642, respectively. The mean diameter of the germinal centers was 102-108 micrometer, but its size distribution ranged from 50 to 175 micrometer.

A histoquantitative study on the effects of castration on the rat ventral prostate lobe.

The effects of castration on the rat ventral prostate was studied utilizing an improved histoquantitative technique. Both volumetric fractions of the tissue compartments and their fractional weights, or, 'total amounts', were calculated during an observation period of 30 days. In addition, the surface area, length and mean diameter of the glandular tubules were recorded. The changes in the mean free distance between the tubules were recorded. The changes in the mean free distance between the tubules ('thickness' of the interacinar tissue) and the mean distance between the glandular centres were also determined. It was observed that the prostatic epithelium was quickly reduced in thickness after castration, to one half at day 2. Decline of the fractional amount of the lumen was slower; it also reached below the 10% level at day 30. The amount of interacinar tissue first increased at 12 hours by one third, but from then on decreased to one third of the normal amount. The 'thickness' of the stroma almost doubled, which was probably due to the sum of the simultaneous marked decline in the diameter of the tubules to one third of the original and the less striking reduction to two thirds of the mean distance between the glandular centres. The morphometrical method ensured the acquisition of a quantitative insight into the tissue processes involved in prostatic atrophy. Calculation of the fractional weights was regarded as especially invaluable, inasmuch as a growing body of evidence has been accumulated in favour of the crucial role of stromal-epithelial interactions in the differentiation, and growth, of the prostate.

Humoral immunodeficiency in chickens induced by chemical bursectomy with colchicine applied on the anal lips.

Colchicine was applied on the anal lips of chickens on 4 consecutive days after hatching. At the ages of 4 and 10 weeks the agglutinin responses to Brucella abortus and to sheep red blood cells (SRBC) after intraperitoneal and per anum immunization were decreased in these animals. IgG and IgM antibodies to Brucella, measured by enzyme-linked immunosorbent assay (ELISA), were also diminished in 12-week-old chickens. The total concentration of plasma IgG, measured by the ELISA-inhibition method, was diminished whereas the IgM level was not influenced by the colchicine treatment. These results broadly resemble the findings after surgical bursectomy or cyclophosphamide treatment. It can be concluded that colchicine applied on the anal lips of chickens causes a long-lasting deficiency of humoral immunity and thus seems to be a useful new tool in the exploration of the humoral-immune functions of the chickens.

A morphometrical study of chicken spleen with special reference to the bursa dependence of the white pulp.

Histoquantitative methods were applied to the study of the bursa dependence of the while pulp structures of normal chickens and chickens bursectomized neonatally by surgical means or chemically by the anal application of colchicine solution. The morphometrical analysis of the spleens from 6- and 12-week-old bursectomized chickens showed that the amount of the white pulp tissue and its compartments, periellipsoidal lymphoid tissue (PELT), periarteriolar lymphoid tissue (PALT) as well as the number of the germinal centers (GC), were decreased, when compared to the controls. The perivenous lymphoid tissue (PVLT) seemed not to be affected by the bursectomies. The results indicate that the PELT, PALT and GCs are bursa-dependent structures of chicken spleen, whereas the PVLT seems to be bursa-independent.