Ambulatory blood pressure measurement in type-II diabetic patients with autonomic neuropathy

The aim of our study was to access the 24-hr ambulatory blood pressure (BP) in diabetic patients with autonomic neuropathy (AN). Twenty-two NIDDM patients without hypertension, being treated with sulfonylureas, were studied. The 24-hr ambulatory blood pressure recordings were performed using portable non-invasive automatic system. Autonomic neuropathy was assessed by standard cardiovascular reflex tests. There were ten patients with and 12 without AN, matched for age, body mass index, duration of diabetes and glycemic control. Mean BP increased at night in four of the subjects with AN and decreased in the remaining 18 patients. The group of subjects with nocturnal increases in BP had more severe autonomic nerve dysfunction compared with those with decreases in nocturnal BP. No significant difference between clinical and ambulatory day-time measurements was found. In three patients with AN after 5 weeks intensified therapy. 24-hr BP did not show any significant difference.     

Cholecystokinin and pancreatic polypeptide release in diabetic patients with and without autonomic neuropathy

The present study was undertaken to investigate postprandial responses of cholecystokinin (CCK) and pancreatic polypeptide (PP) and their interrelationship in patients with diabetes mellitus (DM) with and without autonomic neuropathy (AN). Twenty-two patients with DM (seven with AN and 15 without AN) and 14 age-matched healthy controls were studied. AN was diagnosed according to several tests of cardiovascular autonomic function. CCK and PP plasma levels were measured by specific radioimmunoassays before and at several time points after the oral administration of a test meal. Basal CCK plasma levels in DM patients were normal, whereas basal PP plasma levels were increased (139 +/- 18 vs 72 +/- 7 pg/ml; P < 0.01). Integrated postprandial CCK response was increased in DM patients (208 +/- 27 vs 110 +/- 14 pmol/liter/2 hr; P < 0.05), mainly due to the patients with AN. Postprandial PP response was increased in DM patients without AN (37,273 +/- 5241 vs 13,418 +/- 3299 pg/ml/2 hr; P < 0.001) but not in those with AN (8887 +/- 3461 pg/ml/2 hr). Moreover, PP response was closely (P < 0.002) correlated with the degree of AN. A direct and linear correlation between postprandial CCK and PP responses was found in healthy controls (r = 0.78; P < 0.005) but not in DM patients. We conclude that the CCK response to a meal is increased in diabetic patients with AN, whereas the PP response is increased only with an intact autonomic nervous system.(ABSTRACT TRUNCATED AT 250 WORDS)     

MRI findings in patients with acute autonomic and sensory neuropathy

Acute autonomic and sensory neuropathy (AASN), characterized by acute onset of extensive autonomic dysfunction and severe sensory deficits, was first described by Colan et al. (1978). We present two female patients with AASN in whom magnetic resonance imaging (MRI) confirmed such findings in the posterior column of the spinal cord. One patient was a 44-year-old woman who developed an upper respiratory tract infection followed in 2 weeks by numbness of the limbs and gait disturbance. There was orthostatic hypotension with syncope, paretic ileus, anhidrosis and urinary retention. There was a loss of sensation over the entire body, including the face, and deep tendon reflexes were generally absent. Neurophysiologic studies showed that sensory nerve action potentials and SSEPs were not evoked in the nerves examined. Sural nerve biopsy demonstrated severe axonal degeneration of the myelinated and unmyelinated fibers. Our second patient, a 27-year-old woman, exhibited similar clinical and laboratory features. The autonomic dysfunction in both patients improved gradually without drug treatment, but the sensory deficits--predominantly a loss of deep sensation--persisted for several years. In both patients, MRI revealed the T2*-weighted high intensity area in the fasciculus gracilis of the posterior column of the spinal cord. Such high intensity areas were present in all spinal segments. The severe and persistent sensory disturbance in these patients may have been caused by a lesion of the posterior column of the spinal cord following the involvement of the dorsal root ganglion cells, or ganglioneuronopathy, as demonstrated by MRI.     

Immunocytochemical and electron-microscopic features of tooth pulp innervation in hereditary sensory and autonomic neuropathy

Increases in urine drug concentration that result from changes in urinary output may be mistakenly interpreted as new drug use rather than carryover from previous drug exposure. Normalization of drug excretion to urine creatinine concentration reduces the variability of drug measurement attributable to urine dilution. A specimen ratio of 1.5 or greater between two creatinine normalized positive urine cannabinoid tests was previously proposed as an indicator of new marijuana use. This approach has received wide attention for potential use in treatment and employee assistance programs associated with workplace drug testing. Unfortunately, there has been limited evaluation of the usefulness of this ratio under controlled-dosing conditions with marijuana smokers. A controlled clinical study was conducted to examine the excretion profile of creatinine and marijuana metabolites in a group of six marijuana users who smoked two different doses of marijuana over a 4-week period. A relative operating characteristic curve was constructed from sensitivity and specificity data for 26 different specimen ratios ranging from 0.1 to 2.0. The most accurate specimen ratio (85.4%) for differentiating new use from residual excretion was 0.5. Use of this ratio provided a sensitivity of 80.1%, a specificity of 90.2%, and 5.6% false-positive and 7.4% false-negative predictions. To substantiate the validity of the 0.5 specimen ratio, urine cannabinoid and creatinine data from a controlled clinical trial specifically addressing water dilution as a means of specimen adulteration were evaluated. Sensitivity, specificity, accuracy, and percent false-positive and percent false-negative predictions were 71.9%, 91.6%, 83.9%, 5.4%, and 10.7%, respectively. These data compared favorably with the results from the first clinical study, with the exception of slightly lower sensitivity and higher false-negative percentages in the water dilution study. This would be expected because of the ingestion of large amounts of water and consequent dilution of urine drug concentration. These data indicated that selection of a specimen ratio to evaluate sequential creatinine normalized urine drug concentrations can improve the ability to distinguish residual excretion from new marijuana usage. The selection of an appropriate specimen ratio can be made based on the needs of a specific urine drug-testing program taking into account sensitivity, specificity, and accuracy data.     

Provocation of postural hypotension by insulin in diabetic autonomic neuropathy

The effect of insulin administration on blood pressure has been investigated in eight diabetes with autonomic neuropathy. Systolic and diastolic pressures fell considerably after insulin in all of them. This effect was aggravated by tilting to the vertical position. Five patients fainted when upright with systolic blood pressures less than 50 mm. Hg. This hypotensive effect of insulin occurs whether it is administered intravenously, intramuscularly, or subcutaneously. The onset of the effect is almost immediate after intravenous insulin, is progressive, and may last for several hours. It coincides with a falling blood glucose level and occurs before hypoglycemic levels are reached, and it may be present when the blood glucose level is still elevated. Diurnal variations of postural hypotension have been recorded in some patients, the standing blood pressure falling with the onset of insulin action and rising again as the latter declines. Some of our patients were unable to differentiate between symptoms of hypoglycemia and hypotension. Postural hypotension may account for some episodes of sudden loss of consciousness without warning, usually attributed to hypoglycemia.     

Axonal cytoskeletal pathology in aged and diabetic human sympathetic autonomic ganglia

Prevertebral sympathetic ganglia develop markedly enlarged argyrophilic neurites as a function of age, gender and diabetes. Immunolocalization studies demonstrate their preferential labeling with antisera to highly phosphorylated 200 kDa neurofilament (NF-H) epitopes, NPY, peripherin and synapsin I, but not to hypophosphorylated NF-M and NF-H or MAP-2. The immunophenotype of dystrophic neurites in conjunction with the results of histochemical and ultrastructural studies are consistent with the terminal axonal and/or synaptic origin of neuritic dystrophy in the sympathetic ganglia of aged and diabetic human subjects.     

Association of relative nocturnal hypertension and autonomic neuropathy in insulin-dependent diabetic children

Twenty-four hour BP and heart rate measurements were carried out in fourteen newly diagnosed-, and in twenty-eight diabetics with 5-13 years of duration; and in eight healthy control children. Mean arterial BP rose at night in five-, fell slightly (less than 10%) in five- and fall markedly (more than 10%) in eighteen diabetics with longer duration of the disease. The diurnal-nocturnal difference of mean arterial pressure was significantly lower in the groups with nocturnal BP rise and slight nocturnal BP fall, compared to the control group (< 0.001; p < 0.01, respectively). The diurnal-nocturnal differences of heart rates were significantly lower in diabetics with relative "nocturnal hypertension" compared to the control group (p < 0.05). The presence of subclinical signs of diabetic autonomic neuropathy was significantly higher in patients with nocturnal BP rise and slight nocturnal BP fall compared to patients with marked nocturnal BP fall and newly diagnosed diabetics (chi squared p = 0.02 and p = 0.01, respectively). In conclusion, the prevalence of autonomic symptoms in diabetic children could be related to change in diurnal/nocturnal arterial BP, however longitudinal studies of ABPM are needed to define, whether patients with abnormal BP profiles are candidates for the development of diabetic vascular disease.     

123I-MIBG myocardial scintigraphy in diabetic patients: relationship with 201Tl uptake and cardiac autonomic function

The purpose of this study is to investigate the effects of aging on the human stretch reflexes. The EMG and torque responses of the stretch reflex of the wrist flexors were evoked by ramp-and-hold mechanical perturbations. The stretch reflexes were recorded at seven test conditions with different stretch velocity and muscle preload. The test results from young and older healthy adult subjects were compared. In average, the absolute amplitude of the short-latency (20-40 ms) EMG (recorded from flexor carpi radialis) reflex response was significantly lower in the older group. If the data were normalized and expressed in percentage of the maximal voluntary EMG activity, however, this group difference was not significant. There was no change in the reflex gain of the short-latency reflex with aging. For the long-latency (50-90 ms) EMG reflex response, both the normalized amplitude and the reflex gain were significantly enhanced with aging, probably through supraspinal mechanisms. There was no significant difference in the threshold velocity for the evoked EMG reflexive activities between age groups. There were also no changes in the reflexive wrist flexion torque with aging. These results suggested that the number of motor units recruited during the stretch reflex activity declined with aging although the percentage of motor units recruited was not affected by aging. It is concluded that the central regulating mechanisms of the spinal motoneuron excitability are not compromised by aging. The automatic gain compensation phenomenon is also preserved with aging.     

The effect of hyperbaric oxygen on ophthalmic artery blood velocity in patients with diabetic neuropathy

We investigated changes in the blood velocity of the ophthalmic artery to observe its relationship to the complication of diabetes mellitus before and after hyperbaric oxygen therapy (HBO). Color Doppler imaging (Toshiba, SSA-260A) was used. In this study, there were 7 diabetic neuropathy patients, 3 diabetes patients without neuropathy, and 7 normal subjects for control. These patients were examined before and after HBO. The patients were made to breathe 100% oxygen at 2.0 atmosphere absolute (ATA) for one hour. HBO is sometimes used for treatment of diabetic neuropathy. HBO produced an average decrease in blood velocity of 15.0 +/- 9.0 (mean +/- standard deviation) % in normal subjects, 10.7 +/- 8.6% in diabetes patients without neuropathy, and returned to the baseline level 4 hours after the conclusion of HBO. On the other hand, the blood velocity increased by about 20.6 +/- 9.5% in diabetic neuropathy patients regardless the degree of severity of diabetic retinopathy. These results suggest that the increase in the blood velocity of the ophthalmic artery after HBO in diabetic neuropathy patients could be attributed to an imbalance in autonomic nervous function.     

Corrected QT interval in relation to the severity of diabetic autonomic neuropathy

The aim of this study was to investigate to what extent the existence of objective signs of diabetic autonomic neuropathy affects the corrected QT interval (QTc) in diabetic subjects. A total of 105 diabetic subjects (type 1, n = 53; type 2, n = 52) as well as 40 matched (by age and sex) control subjects were studied. All subjects underwent the battery of five Ewing tests. Autonomic neuropathy was diagnosed if two of the five tests were abnormal. In addition, the result of each test was considered as normal (grade = 0), borderline (grade = 1) or abnormal (grade = 2), and on the basis of the sum of the scores we calculated a total score for autonomic neuropathy. The QTc interval was measured at rest, and a value > 440 ms was considered abnormal. The QTc interval was significantly more prolonged in diabetic persons with autonomic neuropathy than in those without neutopathy and in control subjects: 408.4 +/- 24.2 ms vs. 394.6 +/- 27.9 ms and 393.6 +/- 25.5 ms respectively (P = 0.001). Furthermore, multivariate analysis controlling for age, sex, systolic and diastolic blood pressure, body mass index (BMI), waist-hip ratio (WHR), smoking, type and duration of diabetes, type of treatment, HBA1c and total score of autonomic neuropathy eliminated the role of all these factors as potential confounders except for the total score of autonomic neuropathy, which was found to affect QTc interval independently and significantly (P = 0.012). In summary, the present study confirmed the well-known relation between autonomic neuropathy and QTc interval; in addition, it showed that QTc prolongation is associated with major degrees of autonomic neuropathy.     

Transcranial assessment of maternal cerebral blood flow velocity in patients with pre-eclampsia

BACKGROUND: To clarify the cerebral hemodynamics in pre-eclamptic pregnant women, we investigated the blood flow velocity of the cerebral arteries. METHODS: The mean blood flow velocity and pulsatility index (PI) of the middle cerebral artery (MCA) and internal carotid artery (ICA) in normal pregnant women (n = 35) and pre-eclamptic patients (n = 18) were examined transcranially using pulsed-wave Doppler technique with a 2 MHz probe. In two pre-eclamptic women with post-partum visual disturbance, we examined the mean blood flow velocity and PI of the MCA and ICA every day. RESULTS: The mean blood flow velocity of the MCA in the pre-eclamptic patients (89.7 +/- 20.5 cm/s) was significantly higher than that in the normal pregnant women (53.6 +/- 16.9 cm/s) (p < 0.05). PI of the MCA in the former group (0.67 +/- 0.13) was significantly lower than that in the latter (0.78 +/- 0.02) (p < 0.05). There was no significant difference between these two groups in these variables of the ICA. In the two patients with visual disturbance, the mean blood flow velocity of the MCA was increased before the onset of visual disturbance and decreased gradually following the disappearance of this symptom. In these patients, spasm of the MCA was confirmed by magnetic resonance angiography. CONCLUSIONS: In pre-eclamptic patients, we found increased MCA mean velocity before the onset of visual disturbance. Transcranial Doppler may be useful for the evaluation of cerebral hemodynamics and the prediction of eclampsia.     

Prevalence of central autonomic neuropathy in elderly dialysis patients

BACKGROUND: Autonomic neuropathy is frequently present in dialysis patients. In addition, deterioration of autonomic function occurs with ageing. This study examines the true prevalence of autonomic neuropathy in elderly dialysis patients and questions whether the combination of age and uraemia further increases the chance of dysautonomia being present. METHODS: We compared the results of five different tests (30:15 ratio; Valsalva ratio; heart rate response to deep breathing and the blood pressure responses to sustained hand grip and standing) of parasympathetic and combined parasympathetic and sympathetic dysfunction in older haemodialysis patients (mean age 70.2 years), younger haemodialysis patients (mean age 48.1 years) and two groups of subjects with normal renal function (mean age 73.0 years and 42.5 years respectively). RESULTS: Parasympathetic dysfunction was most prevalent in older patients on dialysis (65.9% (95% confidence intervals 51.4-80.4%), compared with 33.3% (95% confidence intervals 19.0-47.5% in younger dialysis patients), and 11.8 and 0% in the old and young control groups respectively). Combined parasympathetic and sympathetic dysfunction was seen in 41.5% (95% confidence intervals 26.5-56.5%) and 11.9% (95% confidence intervals 2.1-56.5%) of the old and young dialysis patients respectively but not in any of the control subjects. No interaction was seen between age and subject type. CONCLUSIONS: We conclude that although older dialysis patients have severe impairment of cardiovascular autonomic innervation, the prevalence of dysfunction is not higher than would be expected in an ageing population with uraemia.     

Scintigraphic assessment of silent myocardial ischaemia after early infarction using myocardial SPET imaging with 201Tl and 123I-MIBG

To test the hypothesis that myocardial sympathetic denervation reflects silent myocardial ischaemia early after infarction, 12 patients with myocardial infarction but without post-infarction angina pectoris underwent single photon emission tomography (SPET) at rest with 201Tl and 123I-metaiodobenzylguanidine (MIBG) shortly after and 3 months after infarction. Short-axis SPET images at the basal, mid-ventricular and apical portions of the left ventricle were selected, and each short-axis image was divided into eight segments. Tracer uptake in each of the 24 segments was scored using a 4-point scale. The total score in each segment was calculated as the defect score for each image, and the difference between the total defect score for the 201Tl and 123I-MIBG images was calculated as the delta defect score. All 12 patients underwent exercise stress 201Tl scintigraphy 1 month after infarction, and they were divided into two groups: those patients with (Group A, n = 7) and those patients without (Group B, n = 5) transient perfusion defects in the peri-infarcted region without chest pain. For the 123I-MIBG defect score, a marked reduction at 3 months was observed in Group A (24 +/- 12 vs 13 +/- 6; P < 0.01), whereas the defect score remained unchanged in Group B (25 +/- 7 vs 23 +/- 8; N.S.). The delta defect score was significantly reduced in Group A (10 +/- 5 vs 6 +/- 4; P < 0.05), whereas it remained unchanged in Group B. The 123I-MIBG defect score early after infarction was higher than the exercise-induced 201Tl defect score (24 +/- 12 vs 20 +/- 9; P < 0.01), whereas at 3 months post-infarction it was lower than the exercise-induced 201Tl defect score (13 +/- 6 vs 20 +/- 9; P < 0.05). Moreover, effort chest pain during daily activities was noted in 5 of the 7 (71%) patients in Group A within 3 months post-infarction. The results of this study suggest that viable but denervated myocardium (mismatched 123I-MIBG defects) is present in peri-infarcted regions, and that myocardial sensory nervous disturbance, which may co-exist with sympathetic nervous denervation, may induce silent myocardial ischaemia in patients with myocardial infarction.     

Psychological stress and blood glucose regulation in Type I diabetic patients.

Investigated whether psychological stress (PS) predicted blood glucose levels (BGLs), independent of self-management, in 15 Type I diabetic patients. Ss self-monitored daily mean BGLs, PS, diet, exercise, and insulin injections for 8 wks. Considerable individual variability in findings was evident, with PS predicting BGLs in a statistically significant manner in 7 Ss. PS had a significant effect on BGLs independent of the effects of diet, exercise, and insulin administration for the 7 Ss. Discussion focuses on the problems of measuring the key self-management behaviors influencing BGLs and on the possibility that a subgroup of diabetic patients may be BGL stress responders. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Relation among stenosis severity, myocardial blood flow, and flow reserve in patients with coronary artery disease

BACKGROUND: Coronary arteriography is considered the "gold standard" for evaluating the severity of a coronary stenosis. Because the resistance to blood flow through a stenotic lesion depends on a number of lesion characteristics, the physiological significance of coronary lesions of intermediate severity is often difficult to determine from angiography alone. This study of patients with coronary artery disease seeks to determine the relation between myocardial blood flow and flow reserve measured by positron emission tomography (PET) and the percent area stenosis on quantitative coronary arteriography. METHODS AND RESULTS: We studied 28 subjects: 18 patients with coronary artery disease (66 +/- 8 years) and 10 age-matched healthy volunteers (64 +/- 13 years) with dynamic N-13 ammonia PET imaging at rest and after dipyridamole (0.56 mg/kg). The percent cross-sectional area stenosis was quantified on the coronary arteriograms as described by Brown et al. In the 18 patients, a total of 41 non-infarct-related coronary vessels were analyzed. Myocardial blood flows in normal regions of patients with coronary artery disease were not different than those in healthy volunteers, both at rest and after dipyridamole. As a result, the myocardial flow reserve was also similar in both groups (2.4 +/- 0.4 versus 2.6 +/- 0.7, respectively; P = NS). Quantitative PET estimates of hyperemic blood flow (r = .81, P < .00001), flow reserve (r = .78, P < .00001), and an index of the "minimal coronary resistance" (r = .78, P < .00001) were inversely and nonlinearly correlated with the percent area stenosis on angiography. Of note, PET estimates of myocardial flow reserve successfully differentiated coronary lesions of intermediate severity (50% to 70% and 70% to 90%; 2.4 +/- 0.4 versus 1.8 +/- 0.5, respectively; P = .04). CONCLUSIONS: In patients with coronary artery disease, non-invasive measurements of myocardial blood flow and flow reserve by PET are inversely and nonlinearly related to stenosis severity as defined by quantitative angiography. Importantly, coronary lesions of intermediate severity have a differential flow reserve that decreases as stenosis increases that can be detected noninvasively by PET, thus allowing better definition of the functional importance of known coronary stenosis.     

Direct and indirect assessment of skeletal muscle blood flow in patients with congestive heart failure

Techniques which are currently used to measure skeletal muscle blood flow (SMBF) in patients with congestive heart failure (CHF) are neither convenient nor accurate. They have led to discrepant results in patients with congestive heart failure and are, in part, responsible for the ongoing debate regarding the factors which limit the rise in body oxygen consumption during exercise in these patients. However, direct measurement of SMBF may not be needed during exercise in patients with severe CHF. Their skeletal muscles maximally extract oxygen. Consequently, increase in oxygen consumption by the skeletal muscles is only mediated by a concomitant increase in SMBF. In patients with severe CHF, peak body oxygen consumption attained during maximal exercise closely depends on the rise in SMBF, and thus provides an indirect measurement of SMBF.     

Early detection of diabetic visceral neuropathy. An electrophysiologic study of bladder and urethral innervation

The segmental and supraspinal innervation of the detrusor muscle and periurethral striated musculature was studied in 27 patients with diabetes mellitus by gas cystometry, integrated sphincter electromyography, and spinal evoked-response latency measurements. Slowing of neural conduction velocities was a consistent finding in all the patients, even when cystometry did not show abnormalities. Thus, neuropathy in the segmental innervation of the bladder and urethra was documented.     

Direct evidence of impaired cardiac sympathetic innervation in essential hypertensive patients with left ventricular hypertrophy

Increased sympathetic nervous activity has been proposed as one of the causes of left ventricular hypertrophy (LVH) associated with hypertension. However, the precise relationship is not fully understood. METHODS: To elucidate the relationship between myocardial sympathetic nervous activity and LVH in patients with essential hypertension EHT), we performed 123I-metaiodobenzylguanidine (MIBG) myocardial scintigraphy in 49 patients with EHT and 17 normotensive control subjects. Sympathetic innervation of the left ventricle was evaluated using SPECT, and the whole heart uptake of the tracer was quantitatively assessed as the heart-to-mediastinum uptake ratio on both the early (15-min) and delayed (5-hr) images. Myocardial washout rate (MWR) of the tracer from 15 min to 5 hr after the isotope administration was also calculated. The left ventricular mass index (LVMI) was determined echocardiographically. RESULTS: In 49 hypertensive patients, there was a negative correlation between LVMI and heart-to-mediastinum uptake ratio on both the early and delayed images (r=-0.55, p < 0.0001; r=-0.63, p < 0.0001, respectively). In addition, there was a positive correlation between the LVMI and MWR of 123I-MIBG in these hypertensive patients (r=0.59, p < 0.0001). As for the regional uptake of the tracer, there was no significant difference between control subjects and hypertensive patients without cardiac hypertrophy, but a significant decrease of the uptake in the inferior and lateral regions was observed in hypertensive patients with cardiac hypertrophy. CONCLUSION: Patients with EHT had decreased accumulation and increased MWR of 123I-MIBG in proportion to the degree of LVH. Hypertensive patients with cardiac hypertrophy had impaired sympathetic innervation in the inferior and lateral regions of the left ventricle.     

Dependency of contractile reserve on myocardial blood flow: implications for the assessment of myocardial viability with dobutamine stress echocardiography

Fox- mutants of Anabaena sp. strain PCC 7120 are unable to fix dinitrogen in the presence of oxygen. A fragment of the DNA of Anabaena sp. was cloned by complementation of a spontaneous Fox-, cyanophage-resistant mutant, R56, and characterized. Random insertion of transposon Tn5 delimited the complementing DNA to a 0.6-kb portion of the cloned fragment. Sequencing of this region and flanking DNA showed one complete open reading frame (ORF) similar to the gene rfbP (undecaprenyl-phosphate galactosephosphotransferase) and two partial ORFs similar to genes rfbD (GDP-D-mannose dehydratase) and rfbZ (first mannosyl transferase), all of which are active in the synthesis of the O antigen unit of the lipopolysaccharide (LPS) component of the outer membrane of gram-negative bacteria. In a transposon (Tn5-1087b)-induced, Fox-, cyanophage-resistant mutant, B14, the transposon was found within the same rfbP-like ORF. The three ORFs were insertionally inactivated with the omega cassette (P. Prentki and H. M. Krisch, Gene 29:303-313, 1984) or with Tn5::omega. Only the insertions in the rfbZ- and rfbP-like ORFs led to resistance to cyanophages A-1(L) and A-4(L) and to a Fox- phenotype. Electrophoretic analysis showed that interruption of the rfbZ- and rfbP-like ORFs resulted in a change in or loss of the characteristic pattern of the lengths of the LPS, whereas interruption of the rfbD-like ORF merely changed the distribution of the lengths of the LPS to one with a greater prevalence of low molecular weights. According to electron microscopy, interruption of the rfbP-like ORF may have led to aberrant deposition of the layers of the heterocyst envelope, resulting in increased leakage of oxygen into the heterocyst. The results suggest that modified LPS may prevent cyanophage infection of Anabaena sp. vegetative cells and the formation of a functional heterocyst envelope.